From ef21a4c6f1d06f35d820487ffaeb7aae6d8dbd34 Mon Sep 17 00:00:00 2001 From: dosumis Date: Fri, 30 Aug 2024 10:42:02 +0100 Subject: [PATCH] Adding validated, approved CellGuide patterns Fixes #2081 #2350 --- .../data/default/ExtendedDescription.tsv | 4355 +++++++++++++++++ .../source_data/CellGuide/CG_desc_proc.py | 20 + ... Validated Descriptions for CL Review.xlsx | Bin 0 -> 647956 bytes .../dosdp-patterns/ExtendedDescription.yaml | 41 + 4 files changed, 4416 insertions(+) create mode 100644 src/patterns/data/default/ExtendedDescription.tsv create mode 100644 src/patterns/data/source_data/CellGuide/CG_desc_proc.py create mode 100644 src/patterns/data/source_data/CellGuide/CellGuide Validated Descriptions for CL Review.xlsx create mode 100644 src/patterns/dosdp-patterns/ExtendedDescription.yaml diff --git a/src/patterns/data/default/ExtendedDescription.tsv b/src/patterns/data/default/ExtendedDescription.tsv new file mode 100644 index 000000000..471f13c5f --- /dev/null +++ b/src/patterns/data/default/ExtendedDescription.tsv @@ -0,0 +1,4355 @@ + defined_class CL_short_form desc pubs +0 CL:0000034 CL_0000034 "Stem cells are a unique type of cell that has the remarkable ability to divide and develop into many different types of cells in the body. These cells are undifferentiated, meaning they haven't yet developed into a specific cell type, and they can renew themselves through cell division. As a result, stem cells have the potential to replace damaged or diseased cells in the body, making them a valuable tool in medicine and research. + +There are two main types of stem cells: embryonic stem cells and adult stem cells. Embryonic stem cells are derived from embryos and can develop into any type of cell in the body. Adult stem cells, on the other hand, are found in various tissues and organs throughout the body and can only develop into certain types of cells. + +Stem cells have numerous potential applications in medicine, including the treatment of various diseases and the repair of damaged tissues. For example, they could be used to replace damaged heart tissue after a heart attack or to repair spinal cord injuries. Stem cells also have potential uses in drug development and disease research, as they can be used to model diseases and test potential therapies in vitro." DOI:10.1016/j.cell.2016.05.043|DOI:10.1016/j.cell.2018.09.010|DOI:10.1038/nm.4502|DOI:10.1016/j.stem.2023.05.015|https://www.mayoclinic.org/tests-procedures/bone-marrow-transplant/in-depth/stem-cells/art-20048117#:~:text=These%20stem%20cells%20are%20manipulated,injected%20into%20the%20heart%20muscle. +1 CL:0000075 CL_0000075 "Columnar/cuboidal epithelial cells are specific types of cells found in the epithelial tissue that are characterized by their cellular shapes and arrangements. + +Columnar epithelial cells are typically elongated and resemble columns, hence their name. These types of cells are primarily involved in secretion and absorption processes. They are often found lining the stomach, intestines, and other parts of the digestive tract, where they secrete digestive enzymes and absorb nutrients from food. Some columnar epithelial cells also have specialized structures like cilia (which help in movement of substances) or microvilli (which increase the cell's surface area for better absorption). + +In contrast, cuboidal epithelial cells, being approximately equal in width and height, appear somewhat square-shaped. Their primary function lies in secretion, absorption, and excretion. They are often found in glandular tissues as these cells help in the production and discharge of various substances. For instance, cuboidal cells constitute the lining of kidney tubules, where they are involved in filtering blood and producing urine. In the thyroid gland, these cells are responsible for hormone production. +" DOI:10.1016/j.cub.2021.07.078|DOI:10.1016/B978-0-12-391448-4.00011-3|DOI:10.1155/2018/2819154|https://www.ncbi.nlm.nih.gov/books/NBK532977/ +2 CL:0000065 CL_0000065 "Ependymal cells are ciliated neuroepithelial cells lining the ventricles of the brain and the central canal of the spinal cord, forming a single-layered epithelium, known as the ependyma. Together with astrocytes, microglial cells, and oligodendrocytes, they are one of the four main types of neuroglia found in the nervous system. + +Ependymal cells are equipped with multiple functions that support the brain and spinal cord. Key amongst these functions are the secretion, circulation, and absorption of cerebrospinal fluid, which cushions the brain, distributes neuroendocrine factors, and disposes of neural waste. The cilia on the apical surface of ependymal cells vigorously beat in a coordinated fashion to circulate the cerebrospinal fluid. Additionally, these cells may also function in aiding the migration of neuroblasts during brain development. + +Ependymal cells form a barrier between the cerebrospinal fluid and the adjacent nervous tissue in the central nervous system, which appears to be particularly important during development. In response to injury, ependymal cells have been observed to proliferate and have the potential to transform into astrocytes or oligodendrocytes, suggesting stem cell-like functions. +" DOI:10.14336/AD.2022.0826-1|DOI:10.1007/s00401-009-0624-y|DOI:10.4161/tisb.28426 +3 CL:0000076 CL_0000076 "Squamous epithelial cells are a specialized type of epithelial cell characterized by their thin, flat and usually polygonal form. They exhibit a distinctive pancake-like shape and are one of the defining types of cells within the epithelial cell family, a diverse and widespread group of cells that play crucial roles in many biological functions. Squamous epithelial cells are mostly found in areas where rapid passage of substances occurs. + +Their primary function is to provide a barrier and to perform a defense role as they form the superficial layer of the skin and the lining of body cavities, including the mouth and esophagus, as well as the blood vessels and organs of the entire body. The barrier function of these cells not only protects the body's tissues against physical and chemical damage but also against pathogens and excessive water loss. + +Additionally, squamous epithelial cells are known for their central role in the diffusion of gases due to their exceptionally thin and flat structure. Such pivotal function is clearly seen in the alveoli of the lungs, where these cells assist in the exchange of oxygen and carbon dioxide between the blood and the breathed-in air. Because of their thinness, molecules can pass through them quickly, making them an ideal component of the selectively permeable membranes in life-sustaining processes such as gas exchange and filtration. + +" DOI:10.2217/17460751.1.1.45|DOI:10.1007/s00418-022-02073-5|https://www.ncbi.nlm.nih.gov/books/NBK532977/|https://pressbooks-dev.oer.hawaii.edu/anatomyandphysiology/chapter/epithelial-tissue/ +4 CL:0000067 CL_0000067 "The epithelial cells of the uterus include different types of cells that play a critical role in reproductive biology, depending on their location within the uterus. The innermost layer of the uterus, known as the endometrium, is constituted of a single layer of luminal epithelial cells, which line the cavity of the uterus, and of columnar glandular epithelial cells, which form tubular glands that reach deeply into the endometrial stroma. + +The primary function of endometrial epithelial cells is to respond to hormonal signals, such as estrogen and progesterone, during the menstrual cycle. These cells undergo characteristic changes in response to cyclic variations in female hormones. During the proliferative phase of the menstrual cycle, rising levels of estrogen stimulate endometrial epithelial cells to proliferate and thicken the endometrium. Following ovulation, in the secretory phase, progesterone secretion triggers differentiation of these cells into a secretory phenotype, which drives preparation of the uterine lining for potential embryo attachment. These secretions are important for embryonic nutrition in the period between implantation and the establishment of the placental circulation. + +Furthermore, communication between the endometrial epithelial cells and the implanting embryo is a critical aspect of successful implantation. The epithelial cells express particular adhesion molecules, cytokines, and growth factors, which facilitate the attachment and invasion of the embryo into the uterine wall. In addition to their role in fertility, changes in these cells can lead to conditions such as endometriosis and endometrial cancer, both of which involve abnormal growth and division of endometrial epithelial cells. + +Other epithelial cells in the uterus include secretory epithelial cells in the cervix, the lower part of the uterus that connects to the vagina. These cells produce mucus, which changes in consistency and composition throughout the menstrual cycle and plays a crucial role in regulating sperm transport and providing a barrier to pathogens, thereby helping to prevent infection. In addition, epithelial cells in the myometrium, a muscular layer of the uterus responsible for contractions during labor and menstruation, help coordinate uterine contractions. +" DOI:10.1016/S0074-7696(04)34003-9|DOI:10.1164/rccm.201301-0059CI|DOI:10.1242/dev.115659 +5 CL:0000077 CL_0000077 "Mesothelial cells are crucial components of the mesothelium, a protective layer that lines the body's internal cavities, including pleural cavity (around the lungs), the pericardial cavity (around the heart), and the peritoneal cavity (within the abdomen). Derived from the embryonic mesoderm layer, these cells exhibit a squamous-like epithelial morphology, usually appearing as a single layer of flat, pavement-like cells in their healthy state. + +Mesothelial cells play a vital role in various physiological processes, such as intraperitoneal immunity, fibrinolysis, tissue repair, and tumor suppression. Their primary function is to provide a slippery, non-adhesive and protective surface to reduce friction and eases the movements of the organs within the pleural, pericardial, and peritoneal cavities, and they participate in the transport and movement of fluid and various molecules across the so-called serosal cavities. + +These cells have adaptive capabilities that facilitate their role in many pathological processes. In response to injury or inflammation, mesothelial cells can undergo morphological and functional changes, such as mesothelial-mesenchymal transitions, aiding in wound healing and tissue repair. Dysfunctions of mesothelial cells, however, can lead to serious health conditions, including adhesions, fibrosis, and malignancies such as peritoneal and pleural mesotheliomas. + +" DOI:10.1016/S1357-2725(03)00242-5|DOI:10.1046/j.1440-1843.2002.00404.x|DOI:10.3389/fphar.2015.00113|DOI:10.1038/s41467-020-16893-3 +6 CL:0000071 CL_0000071 "Blood vessel endothelial cells, also known as vascular endothelial cells, form the delicate inner lining of the complex circulatory system, including arteries and veins. These cells form a single, continuous monolayer inside every blood vessel, acting as a crucial biomolecular barrier between the blood, and the rest of the body tissues. They perform various fundamental biological functions, ranging from maintenance of vessel integrity to blood clotting regulation. Additionally, they control the transportation of fluids, molecules, and blood particulate matter from and into the bloodstream. + +One of the primary functions of blood vessel endothelial cells is to maintain vascular homeostasis - a stable environment within the blood vessels. They accomplish this through several methods: they control vasomotor tone, i.e. the degree of contraction and dilation of blood vessels, by secreting vasoactive substances such as nitric oxide and endothelin; mediate responses to inflammatory stimuli; and they also regulate angiogenesis, the process of new blood vessel formations. Blood vessel endothelial cells play a significant role in preventing blood clot formation by generating a slick, non-thrombogenic surface that disallows platelets or coagulant proteins from adhering to it. + +Blood vessel endothelial cells are sensitive to various stimuli, including shear stress caused by blood flow, and they can respond by altering their morphology, function, and gene expression. This ability to adapt enables blood vessels to remodel and ensure the adequate delivery of nutrients and oxygen to all tissues, regardless of physiological demand variations. Conversely, endothelial dysfunction, often associated with a reduction in the bioavailability of endothelium-derived nitric oxide, can lead to the development of pathological conditions such as atherosclerosis, hypertension, diabetes mellitus, and even aging-related diseases. +" DOI:10.3390/ijms20184411|DOI:10.1038/s41569-022-00770-1|DOI:10.1016/j.biomaterials.2007.01.039|DOI:10.1152/physrev.00001.2017|DOI:10.1007/s00441-021-03471-2 +7 CL:0000079 CL_0000079 "Stratified epithelial cells form layers of cells stacked on top of one another, and they primarily function as a protective barrier. Their appearance can be cuboidal, columnar or squamous, and they offer a layer of defense against foreign bodies, harmful substances, pathogens, and prevent water loss and electrolyte imbalance within the body. Depending on the organ and its specific function, the topmost layer of these cells may be specialized as keratinized or non-keratinized. The skin, being constantly exposed to external physical stress, is composed of keratinized stratified epithelial cells that prevent desiccation and provide additional protection. In contrast, non-keratinized stratified epithelial cells line internally exposed surfaces like the oral cavity, esophagus, and vagina, where lubrication is required. + +In addition to protection, stratified epithelial cells also contribute to tissue repair processes, referred to as epithelialization. Basal epithelial cells are capable of rapid division and migration to heal wounds and maintain the protective barrier function of the tissues they line. Despite having a limited lifespan, these cells ensure a constant replacement process, maintaining their population and the integrity of epithelial layers." DOI:10.1002/wdev.146|https://www.ncbi.nlm.nih.gov/books/NBK534261/ +8 CL:0000082 CL_0000082 "The epithelium of the lungs is a specialized tissue lining the respiratory tract that serves various crucial functions related to respiration and lung health. It consists of a number of different epithelial cell types, each with specific functions. + +Among the main epithelial cell types in the lung are Type I and Type II pneumocytes, which differ in structure and function. Type I pneumocytes are thin and flat squamous epithelial cells which cover more than 95% of the alveolar surface and facilitate the rapid diffusion of oxygen and carbon dioxide between the lungs and the bloodstream. In contrast, Type II pneumocytes, are granular and cuboidal cells that cover the remaining less than 5% of the alveolar surface; their primary function is the production and secretion of surfactant, a lipoprotein complex that lowers surface tension within the alveoli to prevent their collapse during exhalation and facilitate expansion during inhalation. + +Other epithelial cells of the lungs include goblet cells, pulmonary ionocytes, neuroendocrine cells, and others. Lung goblet cells are interspersed among ciliated epithelial cells (found in the bronchi and bronchioles) and produce mucus, which traps dust, particles, and pathogens in the airways and help protect the lungs by facilitating the removal of these particles and pathogens through coughing or ciliary action. Pulmonary ionocytes are a relatively new and rare epithelial cell type which expressed CFTR, the gene that is mutated in cystic fibrosis. Pulmonary neuroendocrine cells make up only 0.4% of total airway epithelial cells but are considered as crucial for oxygen- and chemical/physical stimuli-sensing. + +Collectively, these and other types of epithelial cells enable the essential functions of gas exchange, mucus production, clearance of foreign materials, and protection against pathogens. The coordinated actions of these epithelial cell types are crucial for maintaining lung function and preserving the integrity of the respiratory system. +" DOI:10.1038/s41577-020-00477-9|DOI:10.1016/j.stem.2020.03.009|DOI:10.1164/rccm.201911-2199OC|DOI:10.1038/s41586-018-0394-6|DOI:10.1242/dmm.046920 +9 CL:0000134 CL_0000134 "Mesenchymal stem cells (MSCs) are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts, chondrocytes, myocytes, and adipocytes. These cells originate mainly from the mesoderm of the embryo, which forms connective tissues, muscle, and the circulatory and urinary systems. However, in adults, MSCs are found in multiple tissues, including bone marrow, adipose tissue, the umbilical cord, and dental tissues. + +The primary function of MSCs is to maintain and repair the tissues in which they are found. When damage occurs, the MSCs are able to migrate to the site of injury, where they aid in regenerating the damaged tissue by differentiating into the required cell type and by secreting growth factors that enhance tissue repair and reduce inflammation. Furthermore, MSCs can also act as immunomodulators, suppressing immune reactions and reducing inflammation, both locally and systemically. + +Apart from their role in tissue maintenance and repair, MSCs are integral to the field of regenerative medicine and are being investigated for their therapeutic potential in various clinical settings. Owing to their multipotent nature, immunomodulatory activity, and the relative ease of isolation, these cells can be engineered and translated into therapies to treat a variety of diseases, including bone and cartilage defects, liver diseases, heart disorders, and autoimmune diseases, amongst others. They have also been used as vectors for anticancer agents and in cell and gene therapy applications." DOI:10.1038/s41536-019-0083-6|DOI:10.1038/nri2395|DOI:10.1038/cdd.2013.158|DOI:10.3727/096368910X +10 CL:0000158 CL_0000158 "Club cells, originally termed Clara cells, are specialized nonciliated epithelial cells primarily located in the bronchioles, or small airways, of the lungs. Compared to other cells in the lung epithelium, they are distinguished by their characteristic dome shape often marked by short, microvilli-like projections (but no cilia). Underneath their dome-like apex, they possess a large amount of cytoplasm containing numerous granules, and they have a round, centrally located nucleus. Their name 'club' was adopted to signify their appearance, which resembles a club or goblet. + +Club cells perform various crucial roles in maintaining the homeostasis of the respiratory tract. Among their functions is the production and secretion of a variety of proteins, including the club cell secretory protein (CCSP), which plays a role in the immune response of the lungs, particularly, in mitigating inflammation. The secretion of surfactant proteins by these cells also contributes to reducing surface tension in the alveoli, thus facilitating the process of gas exchange. Besides helping to defend against oxidative stress and inflammatory response, surfactants also aid in preventing the air sacs in the lungs from collapsing. + +Another vital role of club cells is their capacity to self-proliferate and differentiate into ciliated cells or basal cells, highlighting their regenerative capacity. This quality is especially critical for maintaining the integrity of the epithelial layer in the lung following any injury or inflammation, aiding the lung tissue to recover and restore its function. Furthermore, it is speculated that club cells might minimize the adverse impact of harmful substances in the air we inhale, thanks to a range of cytochrome P450 enzymes present in them. These enzymes assist in detoxifying harmful substances, a protective mechanism that helps preserve the overall health of the lungs." DOI:10.1378/chest.14-3171|DOI:10.1038/s41467-022-32052-2|DOI:10.2147/JIR.S284800|DOI:10.1152/ajplung.00192.2022|DOI:10.1038/s41385-020-00370-7 +11 CL:0000173 CL_0000173 "Pancreatic D cells, also known as delta cells, are one of the main cell types found in the islets of Langerhans within the pancreas. They represent a minor fraction of the islet cells, comprising about 5% to 10% of the total islet cell population. Their main function is to produce and secrete the peptide hormone somatostatin, an inhibitory hormone that regulates the endocrine system. + +Their complex morphology, coupled with their distinctive function, sets the pancreatic D cells apart from other cells in the islets of Langerhans. They have long, neurite-like processes which allow them to make contact with other pancreatic endocrine cells at some distance from the cell body and create an extensive paracrine network. + +The somatostatin secreted by the pancreatic D cells has a variety of inhibitory effects on the secretory activity of other cells within the pancreas and the gastrointestinal system. In the pancreas, one of the principal roles of somatostatin is to inhibit both insulin and glucagon secretion, thereby playing a potent role in the regulation of blood glucose levels. The processes of pancreatic D cells can be >20μm long and may make contact with multiple pancreatic A and B type cells, potentially explaining the secretion of both glucagon and insulin observed in the presence of somatostatin receptor antagonists. The dual inhibitory role makes somatostatin a key player in preventing the excessive action of these hormones and maintaining metabolic balance. + + +" DOI:10.1038/s41574-018-0020-6|DOI:10.1038/s41467-019-11517-x|DOI:10.1369/0022155415583535|DOI:10.1038/s41574-018-0020-6|https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/delta-cell +12 CL:0000030 CL_0000030 "Glioblasts are primarily found in the central nervous system and are an integral part of the developing and mature brain tissue. They are primitive progenitor cells with the ability to self-renew and can differentiate into neuroglia, including astrocytes and oligodendrocytes, two primary cells involved in neurotransmission and protection of brain tissue. + +When glioblast multiplication is dysregulated, it can lead to harmful manifestations, most notably in the form of an aggressive brain tumor known as Glioblastoma multiforme, one of the most malignant types of neural cancers. +" DOI:10.4252/wjsc.v6.i2.230|DOI:10.1186/s13064-016-0075-9|DOI:10.1073/pnas.97.12.6242|DOI:10.12688/f1000research.22405.1 +13 CL:0000068 CL_0000068 "Duct epithelial cells are distinctly specialized cells that predominantly form the lining of glandular ducts. These cells play a crucial role in the secretion, absorption, and transport of fluids depending on the organ they inhabit. They are typically organized in a tubular structure, forming collectively the conduit for the transport of substances. These cells exhibit tight junctions, enabling the careful regulation of the passage of substances and ensuring that no unwanted particles seep through. They are predominantly characterized by their polarized nature, having distinct apical and basolateral surfaces that support its functions of secretion and absorption. The apical surface, exposed to the duct lumen, is specialized for secretion and interaction with the luminal environment, while the basolateral surface is oriented towards the underlying tissue, facilitating interactions with neighboring cells and the extracellular matrix. + +The ducts serve as the bridge between the gland and the site of secretion, allowing the substances produced by the gland to exit into the body. Thus, duct epithelial cells have a sweeping role in various physiological functions, ranging from defense against pathogens in the respiratory and digestive tracts, to secretion of digestive enzymes, to milk production in mammary glands. + +As a result of their specialized function, any impairment in the function of duct epithelial cells to function properly often leads to certain diseases or disorders. Studies have identified potential correlation between malfunctioning duct epithelial cells and conditions such as cystic fibrosis, chronic obstructive pulmonary disease, and certain cancers, particularly breast and pancreatic. +" DOI:10.4161/tisb.25718|DOI:10.1038/s41467-018-04334-1|DOI:10.1513/AnnalsATS.201402-049AW|DOI:10.3389/fphar.2019.00074|https://www.sciencedirect.com/topics/medicine-and-dentistry/mammary-epithelium +14 CL:0000066 CL_0000066 "Epithelial cells form the epithelium, a protective tissue layer that covers the body's external surface, internal cavities and organs, and is the major tissue in glands. + +Depending on their location, epithelial cells present diverse forms and functions. Simple epithelial cells, which are a single layer thick, facilitate exchange of substances through diffusion and filtration processes. Stratified epithelial cells are multi-layered and specialize in providing protection in areas subjected to mechanical stress, as seen in the skin, mouth, and esophagus. Cuboidal epithelial cells, found in the kidney tubules and glandular ducts, partake in secretion and absorption, while squamous epithelial cells, thin and flat, facilitate rapid exchange of substances as seen in the blood vessels and alveoli. + +Epithelial cells are also critical for secretions and absorptions. Many epithelial cells have microvilli, tiny hair-like structures on their upper surface that increases the cell's surface area, aiding in the absorption process in areas such as the intestines. Other cells, called ciliated epithelial cells, have a layer of moving cilia on their surface useful for moving mucus and trapped bacteria out of the lungs. Furthermore, some epithelial cells form glands that produce various essential secretions such as sweat, hormones, and digestive enzymes. The structural and functional diversity of epithelial cells underscore their significance in maintaining overall body health and homeostasis. +" DOI:10.1002/wdev.146|DOI:10.1155/2018/2819154|DOI:10.1038/nri3608|https://www.ncbi.nlm.nih.gov/books/NBK559063/ +15 CL:0000132 CL_0000132 "Corneal endothelial cells are specialized cells located on the innermost layer of the cornea, known as the endothelium. The cornea is the clear outer layer of the eye that helps to transmit and focus light into the retina. The endothelium is crucial in maintaining corneal clarity by actively pumping water out of the corneal stroma, the thick, collagen-containing middle layer of the cornea, to prevent swelling and ensure transparency. + +Corneal endothelial cells are characterized by their unique hexagonal shape forming a mosaic, and they are highly metabolically active. Their primary function is to maintain corneal dehydration and thereby clarity through maintaining a barrier and an active 'pump-leak' mechanism, which regulates fluid and solute transport. This transport sustains the deturgescence (state of being non-swollen) of the corneal stroma, since stromal swelling can cause corneal opacification, hindering light transmission. Importantly, human corneal endothelial cells have limited regenerative capacity, so damage to them, through disease, aging, or surgical trauma may result in vision loss. +" DOI:10.1097/j.jcrs.0000000000000650|DOI:10.4103/ijo.IJO_646_17|DOI:10.1038/s41598-020-64311-x|DOI:10.1016/j.exer.2011.06.004 +16 CL:0000136 CL_0000136 "A fat cell, also known as an adipocyte, is a specialized type of connective tissue cell responsible for the storage of fat in the body. These cells can be found throughout the body, but are most densely located in adipose tissue, such as the subcutaneous tissue beneath the skin and around organs, and act as the body’s energy storage units. + +The primary function of fat cells is to store energy in the form of fat, also known as triglycerides, for use during periods of caloric deficit. When we consume more calories than we use for energy, our bodies convert the excess energy into fat and store it in adipose tissue. + +Fat cells also play a role in regulating energy balance by secreting hormones, such as leptin and adiponectin, which help to regulate appetite and metabolism. Fat calls have also been implicated in the development of obesity-related diseases, such as insulin resistance and type 2 diabetes. + +Finally, fat cells have been found to play a role in the immune system by secreting cytokines, which can either promote or inhibit inflammation depending on the type of cytokine produced. +" DOI:10.1091/mbc.e15-10-0749|DOI:10.1098/rstb.2006.1859|DOI:10.1007/s10753-021-01559-z +17 CL:0000165 CL_0000165 "Neuroendocrine cells are a unique type of cell that have characteristics of both nerve cells (neurons) and endocrine cells. They are typically involved in the release of hormones into the blood in response to neural stimuli, thereby facilitating communication between the nervous system and the endocrine system. + +The functions of neuroendocrine cells are diverse, reflecting the variety of hormones they produce and processes they regulate. They are found throughout the body, including in the pancreas, adrenal glands, pituitary gland, thyroid, gastrointestinal tract, and the brain. For example, in the pancreas, they produce and release insulin and glucagon, which are critical for regulating glucose metabolism. In the gastrointestinal tract, neuroendocrine cells regulate the secretion of gastric juices and the operation of the gastric muscles that mix and propel the contents of the gut. + +Neuroendocrine cells also play a critical role in homeostasis, maintaining the body's equilibrium in response to changes in the environment. For instance, they help to control blood pressure, fluid balance, and the rate and force of heart contractions. Despite their small number, they are essential for a wide variety of processes including growth, reproduction, and responses to stress. Malfunction of these cells can lead to serious conditions such as neuroendocrine tumors and carcinoid syndrome, underlining their crucial role in human health and disease. +" DOI:10.1038/nrn2647|DOI:10.1016/j.neo.2017.09.002|DOI:10.1016/j.devcel.2020.09.024|http://www.hormones.gr/539/article/neuroendocrine-targets-of-endocrine-disruptors%E2%80%A6.html +18 CL:0000150 CL_0000150 "Glandular epithelial cells are specialized cells that form the functional components of glands, which are integral parts of exocrine and endocrine systems in the body. These cells are found lining the organs and tissues throughout the body and, depending on the type of gland, are responsible for the production and excretion of specific substances like hormones, mucus, sweat, oil, or digestive enzymes. + +In exocrine glands, such as sweat glands, mammary glands, and salivary glands, glandular epithelial cells help in the secretion of substances directly onto an epithelial surface or into a duct leading to the exterior of the body. This aids in many functions including, but not restricted to, the regulation of body temperature, lubrication of surfaces, or break-down of food substances. + +In endocrine glands like thyroid, adrenal, and pituitary glands, glandular epithelial cells are involved in producing hormones and releasing them directly into the bloodstream. This facilitates the communication between cells and the regulation of various bodily functions, including growth, metabolism, and homeostasis. + +In terms of structure, these cells can exist in different forms depending upon their functionality and location. Glandular epithelial cells with exocrine functions typically organize into unicellular or multicellular units forming tubular, acinar, or tubuloacinar structures, while those within endocrine glands are often organized into clusters or cords intermixed with capillary networks for efficient bloodstream secretion. + +Glandular epithelial cells show a high degree of adaptability and differentiation potential, depending on the needs of the organism. This versatility allows them to maintain the homeostasis of the body and respond to different physiological conditions. +" DOI:10.1007/978-3-319-41873-5_6|https://www.ncbi.nlm.nih.gov/books/NBK542322/|https://openstax.org/books/anatomy-and-physiology-2e/pages/4-2-epithelial-tissue +19 CL:0000171 CL_0000171 "Pancreatic A cells, also known as alpha cells, are one of the main endocrine cell types found within the islets of Langerhans in the pancreas. Functionally, these cells are pivotal in glucose metabolism and homeostasis, accounting for about 20% of the total population of cells in the islets. Their primary role involves the synthesis, storage, and secretion of the peptide hormone glucagon, which is critical in energy regulation throughout the body. + +In response to a decrease in blood glucose levels, the pancreatic A cells are stimulated to secrete glucagon into the bloodstream. Glucagon acts on its target cells, mainly in the liver, to stimulate glycogenolysis and gluconeogenesis processes, thereby increasing blood glucose levels back to normal. In this way, pancreatic A cells play an integral role in maintaining glucose homeostasis and preventing hypoglycemia. + +Pancreatic A cells also participate in the local regulation of islet activities as glucagon acts through glucagon receptors on A, B and D type cells within the islets. Recent studies have also shown that Pancreatic A cells play a role in the generation and regeneration of B type cells. Following beta cell injuries pancreatic A cells increase in numbers and produce Glucagon-like peptide-1 (GLP-1), which increases the proliferation and cytoprotection of beta cells. In response to extreme injury of B type cells pancreatic A cells can transform (transdifferentiate) into functioning B type cells. +" DOI:10.1016/j.semcdb.2020.01.006|DOI:10.1016/j.beem.2015.10.002|DOI:10.1677/JOE-08-0290|DOI:10.1210/er.2006-0007|DOI:10.1038/nature08894 +20 CL:0000169 CL_0000169 "Type B pancreatic cells, also known as beta cells, are one of the endocrine cell types located in the pancreas. They represent 70-80% of the cells in the islets of Langerhans, the endocrine part of this organ. Unique to mammals, Type B pancreatic cells are the predominant cell type in the pancreatic islets (50–80% of all islet endocrine cells) and play a crucial role in the body's metabolic regulation and glucose homeostasis. + +The primary function of type B pancreatic cells is the production, storage, and release of insulin, accounting for almost all insulin production in the human body: each cell contains about 20 pg insulin. Insulin has a critical function in regulating blood sugar levels: whenever glucose levels in the blood are high, such as after a meal, type B pancreatic cells secrete insulin to promote glucose uptake into cells, transforming it into usable energy or storing it for later use. Additionally, insulin also inhibits glucose production by the liver, therefore lowering blood glucose levels. + +Impaired function of the type B cells is associated with type 1 and type 2 diabetes, metabolic diseases characterized by chronic hyperglycemia. In type 1 diabetes, an autoimmune response leads to the attack of the body’s own type B cells, resulting in the insufficient production and secretion of insulin. In type 2 diabetes, insulin resistance occurs, and type B cells are unable to compensate by producing more insulin. +" DOI:10.1007/s40828-021-00140-3|DOI:10.3389/fcell.2017.00055|DOI:10.1155/2017/1478294|DOI:10.1038/s41574-020-00443-4|DOI:10.3390/ijms22126403 +21 CL:0000185 CL_0000185 "Myoepithelial cells are a specialized type of cell that are mostly found in glandular epithelium, such as the mammary, lacrimal, salivary, sweat, and prostate glands. They are also present in the myoepithelium that lines the alveoli in the lungs. They are noteworthy for their dual nature, as they exhibit properties of both smooth muscles and epithelial cells. Although they form an integral part of both the secretory acini and ducts, they lie distinctly underneath the epithelial cells maintaining a thin, stretched, and flattened morphology. + +Functionally, myoepithelial cells play an important role in facilitating the contractile function of glands, similar to the function performed by smooth muscle cells. They contract to aid in the release of secretions from the glandular tissue into the ducts. In the mammary gland, for example, myoepithelial cells contract to facilitate the ejection of milk during lactation. Moreover, myoepithelial cells also participate in the secretion of proteins that form the basement membrane and constitute part of the extracellular matrix. + +On a broader scope, they also have a vital role in tumor suppression. They have been identified as natural tumor suppressors as they prevent the invasion and metastasis of certain cancer types. For instance, loss or altered function of myoepithelial cells often signals the onset of invasive breast cancer. +" DOI:10.1186/bcr459|DOI:10.3109/10408368709105881|DOI:10.1186/bcr1286|DOI:10.1038/ncponc0450 +22 CL:0000209 CL_0000209 "Taste receptor cells, also known as gustatory receptor cells, are specialized epithelial cells that are responsible for detecting taste stimuli. They also play a role in regulating feeding behavior and nutrient intake by signaling the presence of nutrients or toxins in food. + +These cells are located in taste buds, which are small structures found on the tongue, palate, and throat. Each taste bud is composed of 50-100 taste receptor cells, as well as supporting cells and basal cells. + +Taste receptor cells are involved in the transduction of taste stimuli into neural signals that can be interpreted by the brain. They detect five primary tastes: sweet, sour, salty, umami (savory), and bitter. Each taste receptor cell is specialized to detect one or more of these tastes, depending on the expression of specific taste receptors on their membrane. For example, sweet taste receptors bind to sugars and artificial sweeteners, while bitter taste receptors recognize many toxins and alkaloids. Mechanistically, when a taste receptor cell is stimulated by a tastant, it depolarizes and releases neurotransmitters that activate sensory nerve fibers, which then transmit the information to the brain. " DOI:10.1038/nrendo.2015.7|DOI:10.1111/j.1748-1716.2011.02308.x|DOI:10.1038/nrn.2017.68 +23 CL:0000216 CL_0000216 "Sertoli cells, also known as sustentacular cells, are epithelial cells that play a crucial part of the male reproductive system and are situated within the seminiferous tubules of the testes. Functionally, Sertoli cells play diverse and pivotal roles in supporting spermatogenesis, the intricate process of sperm production. To scaffold the developing sperm cells, Sertoli cells morphologically change, interacting directly with the germ cells to provide nutritional support, metabolic regulation, and waste removal, thereby creating an environment conducive to the development of germ cells. + +In addition to their structural function, Sertoli cells also secrete several bioactive molecules with crucial implications for spermatogenesis. These include anti-mullerian hormone (AMH) during fetal life, inhibin, and androgen binding protein (ABP), as well as several growth factors and transport proteins. They also contribute to the immune-privileged status of the testes by forming the blood-testis barrier, safeguarding sperm antigens from the systemic immune response. Given their extensive roles in maintaining testicular function, impairments in Sertoli cell function can lead to male infertility and are implicated in a range of related disorders." DOI:10.1016/j.semcdb.2021.06.016|DOI:10.1038/s41419-019-1782-z|https://www.ncbi.nlm.nih.gov/books/NBK560631/ +24 CL:0000236 CL_0000236 "B cells, also known as B lymphocytes, are a type of white blood cell that play a critical role in the adaptive immune system and innate immune responses. These cells are formed in the bone marrow and are responsible for the production of antibodies, which are proteins that help to recognize and neutralize invading pathogens such as viruses and bacteria. + +B cells express unique receptors on their surface known as B cell receptors (BCRs) that are able to recognize specific antigens. Upon binding to an antigen, B cells undergo clonal expansion and differentiation, giving rise to a pool of antibody-secreting cells that provide targeted protection against the invading pathogen. + +In addition to the production of antibodies, B cells also play important roles in the regulation of the immune response. Through antigen presentation and cytokine secretion, B cells can help to activate and coordinate other immune cells, including T cells and macrophages. B cells also have the ability to undergo a process known as class switching, where they can change the type of antibody that they produce in response to specific signals from the immune system. This process allows B cells to produce different types of antibodies with varying effector functions, including the ability to activate complement or recruit other immune cells to the site of infection. + +" DOI:10.1038/s41577-023-00897-3|DOI:10.1038/nrc.2017.121|DOI:10.1016/j.cell.2019.03.016|https://www.ncbi.nlm.nih.gov/books/NBK459471/ +25 CL:0000232 CL_0000232 "Erythrocytes, also known as red blood cells, are a type of specialized cell that make up the largest percentage of cells in the human body. Erythrocytes are biconcave in shape and lack nuclei and organelles, allowing them to carry oxygen and carbon dioxide through the bloodstream more efficiently. The main function of erythrocytes is to transport oxygen from the lungs to the body's tissues and organs, and to transport carbon dioxide from the body's tissues to the lungs, where it can be exhaled out of the body. Hemoglobin, a protein located inside erythrocytes, is responsible for binding to oxygen. + +Erythrocytes are produced in the bone marrow and have a lifespan of approximately 120 days before they are broken down and recycled by the body. Erythrocytes are regulated by the hormone erythropoietin, which is produced by the kidneys and liver in response to low oxygen levels in the body, thereby stimulating erythrocyte production . + +In addition to their role in oxygen transport, erythrocytes also play a key role in regulating the body's pH levels. Without erythrocytes, oxygen would not be able to be transported efficiently throughout the body and tissues would not receive the necessary oxygen to function properly. Overall, erythrocytes are essential for maintaining the health and homeostasis of the body." DOI:10.1056/NEJM199801223380407|DOI:10.3389/fphys.2021.655393|DOI:10.1016/j.blre.2012.12.003 +26 CL:0000312 CL_0000312 "Keratinocytes are the most prevalent cells in the epidermis, the outermost layer of the skin, accounting for roughly 90% of its cells. They derive their name from the family of proteins called 'keratin', which they produce in abundance, and which is a crucial component of the human skin, hair, and nails. Keratinocytes play a pivotal role in providing skin with its barrier function, protecting the body from environmental damage such as pathogens, UV radiation, heat, and water loss. + +Keratinocytes are epithelial cells that originate from the basal layer of the epidermis. They undergo a continuous lifecycle of proliferation, migration, differentiation, and programmed death (or keratinization). Keratinocytes mature as they ascend from the basal layer, concurrently producing keratin and undergoing changes in their shape, from columnar to squamous (flat). When they reach the outermost layer of the skin, or stratum corneum, these cells have completely switched over their metabolism to produce a large amount of keratin, and have lost their nucleus and cytoplasm, effectively turning into corneocytes, the primary cell type in the stratum corneum. + +In addition to forming the physical barrier of the skin, keratinocytes serve many other functional roles. They participate in the immune response by recognizing and responding to pathogens, activating the body's Langerhans cells (a type of tissue-resident macrophage located in the epidermis). Keratinocytes are also involved in wound healing. When damaged, they respond by increasing their rate of cell division, migration and also the secretion of a variety of cytokines and growth factors that aid in wound closure. Moreover, keratinocytes help the skin to respond to changes in environmental conditions, by increasing the production of melanin in response to UV radiation. +" DOI:10.1046/j.1523-1747.2002.00020.x|DOI:10.1111/j.1749-6632.2009.04363.x|DOI:10.3390/ijms21228790|https://www.ncbi.nlm.nih.gov/books/NBK513299/#:~:text=The%20stratum%20corneum%20is%20the%20outermost%20layer%20of%20the%20epidermis,potential%20and%20undergo%20programmed%20destruction. +27 CL:0000322 CL_0000322 "Pneumocytes, also commonly referred to as alveolar cells, are specialized cells that line the alveoli, the tiny air sacs present within the lungs. These air sacs are the primary sites for the critical exchange of oxygen and carbon dioxide that drives respiratory function. Pneumocytes play a vital role in this process and are categorized into two main types: type I pneumocytes (or type I alveolar cells) and type II pneumocytes (or type II alveolar cells), each of which have their own unique structures and functions. + +Type I pneumocytes are squamous epithelial cells and they account for 90-95% of the alveolar surface area, providing a large and thin layer ideal for gas exchange. They are exceptionally thin, making them the primary cells responsible for the diffusion of oxygen from the air in the lungs into the bloodstream and the diffusion of carbon dioxide from the bloodstream back into the lungs to be exhaled. They are connected by tight junctions, sealing the intercellular space and providing a protective barrier to the lower layers of the lung and bloodstream. + +The role of type II pneumocytes is more complex. These are bigger, cuboidal cells which, although they occupy 5-10% of the alveolar surface area, are essential to lung function and health. Type II pneumocytes are responsible for producing and secreting pulmonary surfactant, a lipoprotein complex that reduces the surface tension at the air-fluid interface in the lungs. This prevents the alveoli from collapsing during exhalation and makes respiration a relatively effortless process. Another crucial function of these cells is their capability to divide and differentiate into type I cells, making them important for repair and regeneration when lung tissue is damaged. +" DOI:10.1016/j.rmed.2010.06.018|https://www.ncbi.nlm.nih.gov/books/NBK557542/|https://www.ncbi.nlm.nih.gov/books/NBK534789/#:~:text=Type%20I%20pneumocytes%20make%20up,alveoli%20and%20the%20blood%20vessels. +28 CL:0000362 CL_0000362 "Epidermal cells constitute the outermost layer of the skin in animals and have a multifaceted role in maintaining the body's overall homeostasis. They originate from the ectoderm and form the epidermis, a stratified squamous epithelium that mostly consists of keratinocytes in various stages of differentiation. The primary role of these cells is to act as a physical barrier, shielding the internal organs, tissues, and system from dehydration, infection, and other external influences such as UV radiation. The thickness and stratification of the epidermis vary with its location in the body, depending on the specific demand for protective function. + +One notable characteristic of epidermal cells is their continuous cycle of renewal. The cells are produced in the deepest layer of the epidermis, known as the basal or germinative layer, where they undergo cell division. As new cells form, they gradually push the older cells towards the skin surface. While ascending, these cells undergo a process known as keratinization, where they become filled with keratin, a protein that provides strength and rigidity. By the time they reach the surface, they are essentially dead and filled with keratin, forming a tough, resistant layer that is regularly shed and replaced by newer cells beneath. This entire process, from cell generation to shedding, usually takes around a month. + +" DOI:10.1146/annurev.cellbio.22.010305.104357|DOI:10.1016/j.tcb.2018.05.002|https://www.ncbi.nlm.nih.gov/books/NBK513299/#:~:text=The%20stratum%20corneum%20is%20the%20outermost%20layer%20of%20the%20epidermis,potential%20and%20undergo%20programmed%20destruction. +29 CL:0000442 CL_0000442 "Follicular dendritic cells (FDCs) are specialized cells found in B cell follicles in secondary lymphoid organs such as lymph nodes and spleen. FDCs play a key role in the immune response by presenting antigens to B-cells, which are responsible for producing antibodies. They accomplish this by acquiring antigens via multiple pathways and retaining them in non-degradative endosomal vesicles which cycle to the cell surface, allowing B-cells to encounter and recognize native antigens. In addition, FDCs secrete various cytokines and chemokines that direct immune cells to sites of infection or inflammation. + +FDCs are unique among immune cells in that they do not originate from hematopoietic stem cells, but rather from stromal cells in the lymphoid tissues. They are characterized by their distinctive shape, with long, branching processes that form a network within the follicle. FDCs are also distinguished by the presence of complement receptors, Fc receptors, and other molecules that enable them to capture and present antigens to B-cells. + +Because of their important role in antigen presentation and immune regulation, FDCs have been studied extensively in the context of infectious diseases, autoimmunity, and cancer. Notably, FDCs appear to function as a reservoir for HIV, contribute to autoimmune pathology by presenting autoantigens, and drive FDC sarcoma." DOI:10.1038/nri3689|DOI:10.3389/fimmu.2016.00225|DOI:10.1002/jcp.30662 +30 CL:0000529 CL_0000529 "Pigmented epithelial cells are primarily recognized as essential components of the eye. They contain pigments such as melanin, which gives these cells light-absorbing capability and contributes to their significant roles in visual functions. +In the retina, retinal pigmented epithelial cells are in a compact arrangement and form part of the Bruch’s Membrane, which separates them from the photoreceptors in the retina. They are highly specialized and their crucial functions in the visual cycle range from phagocytosis, where they engulf and eliminate damaged photoreceptor outer segments, to the transportation of nutrients to the photoreceptor cells. ntioxidant function of RPE cells. Light stress produces ROS. RPE cells absorb light through melanin or eliminate ROS accumulation through antioxidants Retinal pigmented epithelial cells are also involved in the conversion of all-trans-retinol to 11-cis-retinol, a critical step in the visual cycle enabling the detection of light. + +Another type of pigmented epithelial cells, the choroidal pigmented epithelial cells, are not as specialized as the retinal epithelial cells, but they also play a significant role in vision: they absorb scattered light, preventing it from reaching the photoreceptor cells and causing visual distortion. Additionally, these cells have a regulatory function, controlling the fluid and molecule exchange between the retina and the choroid, thus maintaining homeostasis in the eye. + +Pigmented epithelial cells are essential for vision clarity and overall eye health, and damage or loss of these cells, such as in age-related macular degeneration, can lead to irreversible vision loss. +" DOI:10.3389/fphar.2021.727870|DOI:10.1155/2010/190724|DOI:10.1111/febs.16018 +31 CL:0000575 CL_0000575 "Corneal epithelial cells are a specialized cell type that form the outermost layer of the cornea, the transparent dome-shaped tissue that covers the front of the eye. The corneal epithelium is 5-7 cells thick and is comprised of inner basal cells, middle wing cells and superficial squamous cells. + +The corneal epithelium plays a crucial role in the maintenance of corneal transparency, protection against external insults, and the refractive power of the cornea. This cell type is responsible for the formation of tight junctions, desmosomes, and hemidesmosomes, which provide structural support to the corneal epithelium and prevent the infiltration of foreign particles and microorganisms. + +Corneal epithelial cells also have a unique and highly organized cytoskeleton that confers mechanical integrity and limits the penetration of foreign substances. Additionally, corneal epithelial cells secrete a variety of proteins and lipids that help to maintain the hydration and clarity of the cornea. These include mucins, which form a lubricating layer that facilitates blinking and limits dryness, and crystallins, which appear to protect against UV- and oxidative stress-induced apoptosis. + +Dysfunction of corneal epithelial cells due to infections, inflammation, or injury can lead to corneal opacity, scarring, and impaired vision." DOI:10.3390/cells10092302|DOI:10.1016/S1350-9462(98)00001-9|DOI:10.1242/jcs.198119|DOI:10.1016/j.semcdb.2007.09.015|DOI:10.1097/ACI.0b013e32830e6b04 +32 CL:0000584 CL_0000584 "Enterocytes, also known as intestinal absorptive cells, are the most abundant epithelial cell lineage in both the small and the large intestines. They line the interior surface of the intestines form an integral component of the intestinal mucosa. They are responsible for the absorption of nutrients from the lumen of the intestines into the bloodstream. A hallmark feature of these ciliated epithelial cells is their brush border—a dense array of microvilli which increases the cell’s surface area, augmenting its absorptive capabilities. + +Enterocytes play a crucial rule in the digestion process by absorbing nutrients such as carbohydrates, proteins, and lipids. After digestive enzymes have broken complex nutrient molecules into simpler compounds, enterocytes absorb these particles through active or passive transport mechanisms. For instance, after carbohydrates are enzymatically broken down to monosaccharides, D-Glucose and D-galactose are transported across the brush border membrane of small intestinal enterocytes via the cotransporter SGLT1 and leave the cells across the basolateral membrane via the GLUT2 transporter. Similarly, enterocytes play a role in the absorption of fats by packaging them into lipoproteins, which are then released into the lymphatic system. + +Enterocytes are also important for the body's immune response, serving as a barrier between the external environment and the internal systems of the body. They recognize and respond to pathogenic bacteria and toxins that may be in the intestines, actively participating in maintaining intestinal homeostasis and promoting mucosal healing. Additionally, they also secrete compounds that can neutralize harmful substances or pathogens and contribute to the regulation of the gut microbiota, thus playing a vital role in gut health and overall immune function." DOI:10.1111/j.1365-2249.2011.04523.x|DOI:10.1111/imr.12182|DOI:10.1016/S1521-6918(03)00107-0|DOI:10.1007/s11033-023-08535-w +33 CL:0000706 CL_0000706 "The choroid plexus epithelial cell is one of the crucial cell types found in the choroid plexus, a capillary-rich tissue located in the brain's ventricles. These cells are distinctly cuboidal or columnar, organized in a monolayer pattern with tight junctions that form a barrier between the cerebrospinal fluid inside the ventricles and the blood circulating in the choroid plexus. The polarity of these cells is highly specialized. The apical (ventricular) side, facing the cerebrospinal fluid, is characterized by numerous microvilli and cilia, while the basolateral (vascular) side is located adjacent to the choroidal interstitium. + +The main function of the choroid plexus epithelial cells is to produce cerebrospinal fluid, an essential fluid that provides mechanical protection, nutrient delivery, and waste removal to and from the brain and spinal cord. These cells actively transport ions, glucose, and other molecules from the blood into the ventricles, driving the osmotic movement of water and the formation of cerebrospinal fluid. The cerebrospinal fluid turnover rate is remarkably high, with the choroid plexus epithelial cells producing approximately 500 mL each day. + +Another noteworthy function of choroid plexus epithelial cells is their role as a constituent of the blood-cerebrospinal fluid barrier. Their organized pattern and tightly connected structure play a key role in strictly controlling the entry of substances from the blood to the cerebrospinal fluid, thus protecting the central nervous system from potentially harmful substances and fluctuations in blood composition. As such, these cells also serve in the transport of certain molecules into the central nervous system and in the clearance of waste products from the cerebrospinal fluid. Emerging evidence also shows that these cells contribute to brain immune responses acting as immunological sentinels." DOI:10.1523/JNEUROSCI.3258-13.2013|DOI:10.1093/jnen/nlv030|DOI:10.1038/nrn3921|DOI:10.1152/physrev.00004.2013|https://www.ncbi.nlm.nih.gov/books/NBK538156/#:~:text=The%20choroid%20plexus%20has%20a,canal%20of%20the%20spinal%20cord. +34 CL:0000704 CL_0000704 "Endothelial tip cells are a specialized type of cell that play a crucial role in angiogenesis, the formation of new blood vessels from the existing vasculature. These cells are located at the ends of growing capillary sprouts, their position giving them the term ""tip"" cells. +Endothelial tip cells are characterized by a number of attributes which facilitate them to lead the way in angiogenesis: They have a highly dynamic, large, and polarized shape, and they extend numerous long and mobile filopodia, or finger-like projections, which continuously probe the extracellular microenvironment for cues that control the growth and movement of the cells. The filopodia are equipped with several receptors, including Vascular Endothelial Growth Factor Receptor (VEGFR) -2 and -3, which respond to guidance signals during angiogenesis. Their distinctive morphology with a broad leading edge and small cell body trailing behind helps in efficiently moving in the right direction responding to cues. + +The function of endothelial tip cells is fundamental to the angiogenesis process. Guiding the sprouting vessel, they direct the subsequent proliferation and migration of the stalk cells, which follow the tip cells and form the body of the sprout. These tip cells do not proliferate, but instead, dictate the division of stalk cells, leading to the elongation of the sprout. They also help in lumen formation. The guidance and sprouting decisions of endothelial tip cells are critical for creating a functional and efficient network of vessels that can appropriately supply oxygen and nutrients to tissues. Notably, tip cells play a role in pathological conditions such as tumor angiogenesis and eye diseases, making them an important area of research in cell biology and medicine. +" DOI:10.1038/nrclinonc.2009.64|DOI:10.1016/j.semcdb.2014.04.009|DOI:10.1101/cshperspect.a006569|DOI:10.1016/j.devcel.2021.06.021 +35 CL:0000240 CL_0000240 "Stratified squamous epithelial cells are a specific type of epithelial cell that form layers and have a flat shape. These cells are part of the outermost layer of the skin, called the epidermis, and are also found lining surfaces of the body that are subjected to physical or chemical wear and tear, such as the mouth, esophagus, and vagina. The primary role of these cells is to create a barrier that protects underlying tissues from dehydration, abrasion, and infection. + +The stratified squamous epithelium is able to provide a strong, force-resistant barrier due to the stratified arrangement of the cells; it consists primarily of keratinocytes in various stages of differentiation: The basal layer contains cells that continuously divide and push older cells towards the surface. As the cells move up through the layers, they gradually flatten and become filled with a protein called keratin. In high-abrasion areas like the skin, the outer layers of these cells can become so filled with keratin that they die (they become 'keratinized'), providing an even more robust barrier; eventually, they are shed off in a process known as desquamation. + +In addition to forming a protective barrier, stratified squamous epithelial cells also play a part in the immune response. They can recognize pathogens, and in response, release chemical signals that attract immune cells to the site of potential infection. Moreover, they also carry out a variety of interactions with the immune system to ensure that invading pathogens cannot penetrate into deeper layers of the body. +" DOI:10.1016/j.jdermsci.2004.05.004|DOI:10.1038/onc.2010.456|DOI:10.1016/j.jdermsci.2018.01.012|DOI:10.1007/s00281-018-0701-1 +36 CL:0000945 CL_0000945 "Lymphocytes of B lineage, also called B cells, are immune cells that are critical for adaptive immunity, which is the body's ability to respond to specific pathogens or foreign substances. B cells are responsible for producing antibodies, which are specialized proteins that can recognize and neutralize specific antigens. B cells develop in the bone marrow and then migrate to the lymph nodes, spleen, and other lymphoid tissues. + +Upon encountering an antigen, B cells can differentiate into two types of effector cells: plasma cells, which produce large quantities of antibodies, and memory B cells, to ensure a quick response to future encounters with the same antigen. B cells use a unique genetic recombination process to create a diverse repertoire of antigen-specific receptors on their surface, allowing them to recognize an enormous variety of potential antigens. + +In addition to their role in antibody production, B cells also play a critical role in immune regulation. B cells can produce cytokines, which are signaling molecules that can modulate the activity of other immune cells. They can also interact with other immune cells, such as T cells, to coordinate an effective immune response. Dysfunction of B cells can lead to a range of immune disorders, such as immunodeficiency, autoimmunity, and allergy." DOI:10.2215/CJN.09430915|DOI:10.1038/s41577-019-0244-2|DOI:10.1111/imr.13016|https://www.immunology.org/public-information/bitesized-immunology/immune-dysfunction/b-cell-mediated-disease|DOI:10.1007/978-981-15-3532-1_1 +37 CL:0000946 CL_0000946 "Antibody secreting cells, such as short-lived plasmablasts and long-lived plasma cells, form a key component of the adaptive immune system. These cells originate from B-lymphocytes upon exposure to antigens. They are primarily characterized by their capacity to produce and secrete large amounts of antibodies (immunoglobulins) that help to neutralize the pathogens, defining the primary role of these cells in the humoral immune response. + +Antibody secreting cells are found predominantly within the lymph nodes, spleen, and mucosa-associated lymphoid tissues. They are characterized by an extensive rough endoplasmic reticulum, reflecting the high antibody production. The interesting dynamics of these cells, switching from a nonsecreting, antigen-specific B-cell state to a high-rate immunoglobulin-secreting cell state, is a major factor in sustaining an effective adaptive immune system: Derived from a single clone, the secreted immunoglobulins have a unique antigen specificity inherited from the parent B cell. They are able to recognize specific extracellular antigens, aiding in marking harmful invaders such as viruses and bacteria for elimination, either by direct neutralization or by recruiting other immune cells for assistance. " DOI:10.1002/eji.1830161018|DOI:10.1038/nri3795 +38 CL:0000938 CL_0000938 "The CD16-negative, CD56-bright natural killer (NK) cell is a subtype of human natural killer cells that plays a pivotal role in the innate immune response. These cells are identified primarily by the lack of CD16, a low-affinity receptor for the Fc region of immunoglobulins G, and high expression of CD56 protein, a neural cell adhesion molecule, on the cell surface. This unique receptor pattern characterizes the regulatory role of these cells in the immune system and distinguishes them from their counterparts - the CD16-positive, CD56-dim NK cells, which have cytotoxic killing actions instead. + +CD16-negative, CD56-bright NK cells are specialized in immunomodulation and this trait is manifested primarily through the release of substantial amounts of cytokines, including TNF, IFN-gamma, GM-CSF, and especially IL-10, when they interact with specific target cells or in response to stimulation by cytokines such as IL-12, IL-15, and IL-18. Thus, these cells form a significant link between innate and adaptive immunity. + +Furthermore, these cells have tropism for secondary lymphoid tissues, where they frequently interact with dendritic cells, contributing to the modulation of dendritic cell maturation and function. This intimate crosstalk between CD16-negative, CD56-bright NK cells and dendritic cells is crucial for the orchestration of both innate and adaptive immune responses. Hence, while the term 'natural killer cell' may suggest a primary role in cell killing, this particular subset of NK cells exert their effects mainly through immune regulation and interaction with other immune cells." DOI:10.4049/jimmunol.1502570|DOI:10.4049/jimmunol.173.10.6418|DOI:10.3389/fimmu.2014.00159 +39 CL:0002063 CL_0002063 "Type II pneumocytes, scientifically known as alveolar type II cells, are specialized cells that reside within the pulmonary alveoli of the lungs - the minute, grape-like sacs where the critical exchange of oxygen and carbon dioxide occurs. These cells are epithelial in nature and form the lining of the alveoli. They make up approximately 60% of the alveolar surface area, despite being fewer in number compared to type I pneumocytes. The shape of type II pneumocytes is cuboidal, and they are larger than type I pneumocytes. + +The primary function of type II pneumocytes is the synthesis and secretion of pulmonary surfactant, a complex mixture of lipids and proteins essential for lowering surface tension within the alveoli. By reducing surface tension, the surfactant prevents the collapse of the alveoli during exhalation, thereby ensuring the maintenance of proper gas exchange and lung elasticity. These cells also play a critical role in alveolar fluid balance by helping in the removal of excess fluid from the alveolar space. + +Furthermore, type II pneumocytes bear an additional characteristic of being progenitor cells in the alveolar compartment. They can proliferate and differentiate into type I pneumocytes during injury or disease processes, thereby contributing significantly to alveolar repair and regeneration. These cells also play a role in the immune response of the lungs by secreting cytokines and chemokines in response to lung injury or infection. +" https://www.ncbi.nlm.nih.gov/books/NBK557542/|DOI:10.1002/(SICI)1097-0185(20000101)258:1<34::AID-AR4>3.0.CO;2-7|DOI:10.1016/C2013-0-12947-9|DOI:10.1186/rr36|DOI:10.1186/s12931-018-0837-5 +40 CL:0002062 CL_0002062 "Type I pneumocytes, also known as alveolar epithelial cells type I, are specialized cells lining the alveoli within the lungs. Their strategic positioning within the air sacs of the lungs plays a crucial role in gaseous exchange. They cover around 90-95% of the alveolar surface, yet make up only about 40% of the total number of cells in the alveolus. Their unique squamous, or flattened, shape allows for a vast surface area that enables a fast rate of diffusion of respiratory gases, oxygen and carbon dioxide. + +Functionally, type I pneumocytes serve as the site for the critical exchange of gases between the air in the lungs and the blood in the capillaries. These cells are in direct contact with pulmonary capillaries and are therefore primarily responsible for oxygen passing into the bloodstream and carbon dioxide being removed from the bloodstream. It is important to note that these cells are extremely thin and fragile, a feature that promotes easy passage of gases but also renders the cells susceptible to damage. + +A unique critical feature of type I pneumocytes is their inability to divide and proliferate. Should damage to these cells occur, repair and replenishment is addressed through the conversion of another cell type, known as type II pneumocytes, into type I pneumocytes. The role of type I cells is thus highly specific, and strictly aligned with enabling efficient respiration - an essential process for all aerobic organisms. +" DOI:10.1165/rcmb.2021-0421OC|DOI:10.1016/B978-0-7216-0186-1.50012-0|DOI:10.1242/jcs.235556|https://www.ncbi.nlm.nih.gov/books/NBK557542/ +41 CL:0002071 CL_0002071 "Enterocytes of the epithelium of the large intestine are specialized absorptive cells predominant in the lining of this part of the digestive tract. These are columnar epithelial cells, characterized by microvilli, a brush-like border that significantly increases the cell's surface area to maximize nutrient absorption. + +A primary function of enterocytes in the large intestine is the absorption of water. Additionally, these cells play a role in the absorption of metal ions, residual monosaccharides, vitamins produced by intestinal bacteria, and short-chain fatty acids produced by dietary fiber fermentation. In conjunction with goblet cells, enterocytes produce mucins that contribute to the formation of a mucus layer that serves as an extra line of defense against pathogenic bacteria." DOI:10.1038/nri3738|DOI:10.1038/nrgastro.2013.35|DOI:10.1084/jem.20191130 +42 CL:0002079 CL_0002079 "Pancreatic ductal cells are a vital structural component of the pancreas, a principal gland involved in digestion and metabolism. These cells exist as flat or cuboidal epithelial cells, primarily organizing themselves to form a network of ducts throughout the pancreas. They create an integral component of the glands' 'exocrine' component, aiding in the transportation of digestive enzymes from the acinar cells (another type of cells in the exocrine pancreas that produce the enzymes) to the small intestine. + +The primary function of the pancreatic ductal cells revolves around the secretion of bicarbonate ions, contributing to the alkaline pancreatic juice that neutralizes the acidic gastric juice in the duodenum. This action allows for a conducive environment for the activated digestive enzymes to efficiently break down food. Furthermore, the pancreatic ductal cells essentially control the amount of fluid that is released into the duodenum, thereby playing a significant role in maintaining the fluid-electrolyte balance in the body. + +Pancreatic ductal cells can also act as the origin point for several pancreatic diseases. The uncontrolled proliferation of these cells often leads to the formation of pancreatic ductal adenocarcinoma, the most common type of pancreatic cancer. +" DOI:10.1172/JCI57131|DOI:10.1016/j.biocel.2004.07.010|DOI:10.3389/fphys.2011.00036|DOI:10.1016/B978-0-12-385233-5.00002-7 +43 CL:0002088 CL_0002088 "Interstitial cells of Cajal are unique cells located in the gastrointestinal tract, specifically within the muscle layers of the entire digestive system. They have a distinctive stellate or spindle-like shape and were named after the Spanish histologist, Ramón y Cajal, who first discovered them. + +The intricate interplay of interstitial cells of Cajal with smooth muscle cells and enteric neurons orchestrates the rhythmic contractions (known as peristalsis) in the gastrointestinal tract. They generate and propagate the slow waves of electrical activity, providing the fundamental pacing signal. Interstitial cells of Cajal are capable of responding to stretch and other mechanical stimuli, which helps in adapting the frequency and strength of peristalsis as needed. They also play an essential role in relaxations of gastrointestinal tract sphincters, ensuring proper control over the passage of material. + +Moreover, disruption or loss of ICCs contribute to several gastrointestinal motility disorders, underscoring their vital role in digestive health. Lack of or reduced ICCs are reported in various conditions such as achalasia, slow transit constipation, and diabetic gastroparesis. +" DOI:10.1152/ajpgi.00264.2021|DOI:10.1016/S0165-6147(97)01108-5|DOI:10.1038/nrgastro.2016.161 +44 CL:0002144 CL_0002144 "Capillary endothelial cells are particularly essential in the formation and function of capillaries - the smallest and most widespread blood vessels in the body. They play two primary roles: barrier function and transport function. Acting as barriers, they strictly control the passage of nutrients, gases, biological molecules, and cells between the blood and the surrounding tissues. This function not only provides a protective shield to internal organs against potentially harmful substances but also regulates the fluid and solute exchange. In terms of transport, these cells facilitate the diffusion of oxygen and essential nutrients from the bloodstream into the tissues. Concurrently, they allow waste products like carbon dioxide to pass from tissues into the bloodstream for removal, making these cells exceptionally instrumental in maintaining the body’s homeostasis. + +Moreover, capillary endothelial cells are also actively involved in numerous other physiological processes such as inflammation, blood clotting, and angiogenesis. During inflammation, they can specifically express and secrete molecules to attract white blood cells to sites of damage. Similarly, in blood clotting, they produce substances that prevent blood cells from sticking to the vessel wall and deter the formation of unnecessary clots. In angiogenesis, they proliferate and organize the formation of new blood vessels, crucial for wound healing and embryonic development. The disruption of their function contributes to pathological conditions like edema, thrombosis, and several cardiovascular diseases. +" DOI:10.1097/01.CCM.0000057847.32590.C1|DOI:10.1152/ajpheart.00704.2007|DOI:10.3390/ijms20184411 +45 CL:0002187 CL_0002187 "The basal cells of the epidermis make up the innermost layer of the skin, providing an essential structural component to the body's largest organ. These cuboidal-shaped cells are critical to the skin's renewal process, dividing to form new keratinocytes that gradually make their way to the skin’s surface. The migration of these cells creates a protective barrier that impedes damage from environmental factors like sunlight, radiation, and harmful pathogens. + +Basal cells have an additional, pivotal role beyond formation and migration of keratinocytes: they are also directly involved in the production of various types of skin appendages, including hair follicles, sebaceous glands, and sweat glands. Coupled with their prolific regenerative properties, these functions make basal cells vital for maintaining the skin's overall health and vitality. + +Changes and mutations in the formation and growth of basal cells of the epidermis can lead to cancerous lesions. Though usually not life-threatening, early identification is critical to minimizing further tissue damage. +" DOI:10.7748/ns.27.3.35.s52|DOI:10.1186/s41038-016-0064-6|DOI:10.1172/JCI58779|DOI:10.1007/s12015-021-10256-1 +46 CL:0002201 CL_0002201 "Renal beta-intercalated cells are primarily found within the connecting tubules and collecting ducts of the kidneys, which are components of the kidney's complex nephron system. They have distinctive structural characteristic: the presence of abundant mitochondria and densely packed microvilli on the cell's luminal membrane. These physical traits, along with the presence of intracellular vesicle transport machinery, aid in their primary function, which is bicarbonate secretion. + +Beta-intercalated cells utilize a proton ATPase and pendrin, a chloride/bicarbonate transporter on the apical (luminal) surface, for bicarbonate secretion into urine and proton reabsorption into the bloodstream. The bicarbonate ions then help neutralize the pH levels in the later stages of urine and in the blood, thus assisting in the maintenance of body pH levels. + +The activities these cells perform have significant implications for body health, illustrating the essential role they play in renal physiology. Defects or deficits within beta-intercalated cells can lead to a variety of renal disorders, such as distal renal tubular acidosis, a condition characterized by an inability to adequately excrete acid, leading to systemic acidosis. In addition, these cells may also be influenced by illnesses such as metabolic acidosis, where the body is producing excessive quantities of acid or when the kidneys are not removing enough acid from the body. +" DOI:10.2215/CJN.08880914|DOI:10.1172/JCI63492|DOI:10.1073/pnas.1221496110 +47 CL:0002224 CL_0002224 "Lens epithelial cells are specialized cells located in the anterior portion of the eye's lens, a crucial part of the visual system. These cells form a monolayer of cuboidal cells under the lens capsule known as the lens epithelium, which plays several key roles in maintaining the health and functionality of the ocular lens. + +Lens epithelial cells are responsible for the synthesis, metabolism, and transport of various substances that make up the lens fibers. These cells ensure the lens maintains its transparency and refractive properties, crucial to the eye's capacity to focus light onto the retina. Lens epithelial cells are also able to divide and differentiate into lens fiber cells and therefore play a fundamental role in lens growth and development. + +The lenses of some species are able to regenerate; the regeneration ability of lenses in higher mammals is relatively weak, but there has been some progress in using lens epithelial cells as endogenous stem cells to achieve the partial regeneration of lens tissue. + +In pathological conditions such as cataracts, the function and behavior of lens epithelial cells can be disrupted, which can lead to cloudy or opaque areas in the lens that interfere with vision. +" DOI:10.1242/dev.107953|DOI:10.1016/j.isci.2023.106921|DOI:10.3389/fcell.2022.983178|DOI:10.1016/j.preteyeres.2022.101112|DOI:10.1016/j.biocel.2007.10.034 +48 CL:0002236 CL_0002236 "Basal epithelial cells of the prostatic duct are unique cell types found within the prostate gland of mammals. The prostatic duct forms a significant part of the prostate's glandular architecture, facilitating the secretion and flow of prostatic fluid. These basal cells are positioned at the base of the prostatic epithelium, forming a layer beneath luminal cells and adjacent to the basement membrane. Functionally, they play a significant role in maintaining tissue homeostasis, managing secretory activities, and contributing to the overall biological functions of the prostate. + +These basal epithelial cells exhibit a high degree of differentiation. Morphologically, they are characterized by their low columnar or cuboidal shape and exhibit less cytoplasm compared to luminal epithelial cells. A notable feature is their high nucleus-to-cytoplasm ratio and the presence of prominent nucleoli. On a molecular level, these cells are known to express certain distinct markers such as cytokeratin 5 (CK5) and p63, differentiating them from other prostatic cells. +The basal epithelial cells of the prostatic duct also serve as a reserve cell population for the regeneration of the prostate epithelium, particularly upon injury or disease, indicating their role in tissue repair and regrowth. Importantly, these cells are also considered as the cells-of-origin in prostate cancer due to their extended lifespan and genomic stability. +" DOI:10.1242/dev.01384|DOI:10.1016/B978-0-12-801238-3.64595-6|DOI:10.1016/j.celrep.2018.11.086|DOI:10.1309/AJCP5ZC4GQVNWTYR|DOI:10.1002/stem.1094 +49 CL:0002324 CL_0002324 "Myoepithelial cells of the mammary gland are a specialized type of smooth muscle cell that plays a vital role in lactation and the normal functioning of the mammary gland. Their unique elongated, stellate shape allows them to wrap around the ductal and alveolar units of the gland. + +Myoepithelial cells of the mammary gland facilitate the expulsion of milk during lactation in response to signaling by the hormone oxytocin. Due to their cytoskeletal composition of actin and myosin, which mirrors that of smooth muscle cells, these cells are able to contract and advance the milk from the alveoli into the ducts, and eventually to the nipple, enabling breastfeeding. + +Other critical roles of myoepithelial cells of the mammary gland include the maintenance of mammary gland integrity and the suppression of tumor formation. They create a mechanical barrier that separates the luminal epithelial cells from the stromal compartment and play a significant role in the suppression of carcinogenesis; loss or alteration of these cells often paves the way for invasive carcinomas. Moreover, these cell types produce extracellular matrix proteins such as fibronectin that help in the synthesis of the basement membrane, providing structural support to the gland and maintaining its overall health and integrity. +" DOI:10.1186/bcr1286|DOI:10.1186/bcr459|DOI:10.1007/s10911-005-9586-4 +50 CL:0002326 CL_0002326 "The luminal epithelial cells of the mammary gland are a key constituent of the glandular tissue in the mammalian breast. Packed into complex structures known as mammary ducts and lobules, these specialized cell types derive their nomenclature from their location within these units - specifically against the inner surface or 'lumen'. + +The main physiological functions they perform are the synthesis, storage, and secretion of milk. During lactation, these cells synthesize the various macromolecular constituents of milk, such as lipids, proteins, and lactose, which are then secreted into the ductal lumen. An intricately coordinated mix of hormonal activation and signaling pathways, involving prolactin and oxytocin amongst others, regulate this process. Luminal cells also exhibit receptivity towards estrogen, and their proliferation is influenced by estrogen and progesterone. + +Luminal epithelial cells are also engaged in several other key aspects of mammary gland biology. They carry a role in the formation of the ductal tree during the developmental process and are involved in glandular remodeling during pregnancy and post-weaning involution. Furthermore, luminal epithelial cells, just like other cell types in the breast, are susceptible to oncogenic transformation. In fact, the majority of breast cancers, specifically those classified as ductal carcinomas, are believed to originate from this cell population, underlining the pathophysiological significance of these cells. +" DOI:10.1152/physrev.00040.2018|DOI:10.1038/s41467-021-27895-0|DOI:10.1101/gad.242511.114|DOI:10.1186/bcr1411 +51 CL:0002337 CL_0002337 "Keratinocyte stem cells are a subpopulation of cells located in the basal layer, or stratum basale, of the epidermis, in the bulge region of hair follicles, and in sebaceous glands. The primary function of keratinocyte stem cells is to renew the skin tissue, the primary barrier that protects our bodies from external environmental factors. To perform this function, keratinocyte stem cells possess the ability to self-renew, maintaining their population, and to produce transient amplifying (TA) cells, which replicate rapidly and differentiate into keratinocytes. + +The differentiation of keratinocyte stem cells into mature keratinocytes is crucial for skin integrity and health. Specifically, mature keratinocytes give rise to the stratum corneum, the outermost barrier layer of the skin. Throughout this process, keratinocytes produce several types of keratin—structural proteins that contribute to the mechanical resistance and elasticity of the skin. Anomalies in this procedure might lead to a variety of skin disorders, such as psoriasis and skin cancer, highlighting the critical role of keratinocyte stem cells in skin homeostasis. + +In addition to their role in skin homeostasis and wound healing, recent research suggests that keratinocyte stem cells have potential in regenerative medicine, specifically in the treatment of skin injuries and diseases. +" DOI:10.1002/jcp.22275|DOI:10.3389/fimmu.2022.786859|DOI:10.1038/s41467-019-12559-x +52 CL:0002375 CL_0002375 "Schwann cell precursors are a crucial type of cell in the peripheral nervous system, derived from the neural crest during embryogenesis. The primary function of Schwann cell precursors is to differentiate into either myelinating or non-myelinating Schwann cells, both of which are critical in the proper function of the nervous system: myelinating Schwann cells cover axons in a myelin sheath, which allows for quicker and more efficient conduction of nerve signals, while non-myelinating Schwann cells envelope several axons together, effectively aiding slower nerve conduction. + +Schwann cell precursors are also possibly involved in guiding axonal growth during the early development of the nervous system, and they have an inherent potential to form other cell types such as melanocytes, parasympathetic neurons, and endoneurial fibroblasts. + +Growing evidence suggests that there is high plasticity among Schwann cell precursor derivatives during postnatal development and that they play a dynamic role not only in the development of the nervous system but also in its repair and regeneration post injury. +" DOI:10.1016/j.cdev.2021.203686|DOI:10.3389/fnmol.2019.00069|DOI:10.3390/cells11233753|DOI:10.3389/fnmol.2019.00069 +53 CL:0002377 CL_0002377 "The immature Schwann cell is a distinctive, developmental stage in the life cycle of a Schwann cell, which is a type of glial cell that is essential for the formation and maintenance of the myelin sheaths that coat and insulate the axons of neurons, boosting their electrical conducting abilities. + +The immature Schwann cell represents a transitional phase between the immature, proliferative Schwann cell progenitors and the mature, myelinating Schwann cells. The transition to a mature, fully differentiated state happens under the influence of axonal signals and involves significant changes in gene expression; immature Schwann cells are characterized by specific factors including the expression of the S100 protein, a unique marker that differentiates Schwann cells from other glial cells. + +Immature Schwann cells have the potential for extensive proliferation, and they actively interact with axons. During the period of synaptic refinement in development, they can respond to neuronal activity and participate in radial sorting of axons. At the same time, immature Schwann cells further modulate the microenvironment, which helps define axonal diameters and spaces. + +While immature Schwann cells contribute to the initial development and refinement of neural circuits, their maturation to myelinating Schwann cells is vital for the efficient functioning of the mature peripheral nervous system. + +" DOI:10.1101/cshperspect.a020487|DOI:10.4103/1673-5374.211172|DOI:10.1177/1073858415572361|DOI:10.1016/j.cdev.2021.203686|DOI:10.1371/journal.pone.0123278 +54 CL:0002518 CL_0002518 "Kidney epithelial cells, also known as renal epithelial cells, are one of the most significant types of cells present within the kidneys, an organ recognized for its role in maintaining homeostasis in the body. These cells mostly contribute to the functionality of the nephrons, which are the microscopic structural and functional units of the kidney, responsible for filtering blood to produce urine. Kidney epithelial cells are found across the various parts of the nephron, including renal tubules, Bowman's capsule, and the collecting ducts. + +The principal function of kidney epithelial cells is to regulate the content of water, electrolytes, organic solutes, and waste materials in the body by facilitating their selective reabsorption and secretion. Their surfaces possess microvilli to aid in absorption, while their strategic location facilitates the easy transfer of materials between the blood and the urine during the filtration process. These cells are also actively involved in transporting ions such as sodium, potassium, and calcium, hence playing a crucial role in maintaining the body's electrolyte balance. + +The kidney epithelial cells, particularly in the proximal tubule, can also perform endocytosis, a process through which proteins that escaped the filtration in the glomerulus are absorbed and degraded so that the amino acids can be reused by the body. In the acid-base homeostasis, these cells, especially in the distal tubules and collecting ducts, adjust the excretion of hydrogen ions and bicarbonate to maintain the body's pH balance. In summary, the kidney epithelial cells play an indispensable role in maintaining the body's homeostasis, and any defects in these cells can lead to grievous conditions, including kidney failure." DOI:10.1016/S0076-6879(06)19009-6|DOI:10.1146/annurev-physiol-052521-121841|DOI:10.3389/fimmu.2020.578952|DOI:10.1146/annurev-physiol-022516-034234|DOI:10.1083/jcb.201410017 +55 CL:0002538 CL_0002538 "Intrahepatic cholangiocytes represent a subset of the biliary epithelial cells that form a network of tubes in the liver called the biliary tree The intrahepatic cholangiocytes reside specifically in the intrahepatic bile ducts and play a crucial role in liver physiology and bile production and secretion, thereby aiding in the digestion and absorption of fats in the small intestine. These specific cholangiocytes arise from bipotent hepatoblasts, whereas extrahepatic cholangiocytes share an embryologic origin with the ventral pancreas. + +Recent research suggests that there is also heterogeneity within populations of intrahepatic cholangiocytes with different transcriptional profiles, proliferative capacity, and biological function; for example, subpopulations differ in calcium-mobilizing receptors. + +The primary function of intrahepatic cholangiocytes is related to bile formation and maintenance of its flow. In addition to their secretory and absorptive activities, they are involved in the regulation of bile composition, volume, and alkalinization, contributing to the neutralization of the acidic chyme (partly digested food) that enters the intestine from the stomach. Intrahepatic cholangiocytes are also recognized for their role in liver regeneration and repair, often proliferating in response to injury. + +Intrahepatic cholangiocytes take part in certain pathological conditions, like primary biliary cirrhosis and cholangiocarcinoma. Changes in these cells often lead to abnormalities in bile formation and transport, causing cholestatic liver diseases. Overall, the primary and secondary functional activities of intrahepatic cholangiocytes are vital in maintaining liver function, digestive processes, and contributing to the body's response to liver injury. + +" DOI:10.1016/j.gastha.2022.07.015|DOI:10.1016/j.ajpath.2023.02.012|DOI:10.1002/hep.31252|DOI:10.1016/j.biocel.2010.06.020 +56 CL:0002543 CL_0002543 "Vein endothelial cells form a thin layer of squamous cells, the endothelium, lining the interior surface of veins throughout the body. They shape the inner cellular lining of the entire vascular system, including the heart, playing a crucial role in blood circulation. The unique characteristic compact arrangement of these cells enables veins to act as a barrier between the blood (that can contain foreign substances) and the surrounding venous tissue and maintain the integrity of the vascular system. + +The primary function of vein endothelial cells is to control the exchange of substances between the bloodstream and the surrounding tissues. They facilitate selective transportation of molecules depending on their size and solubility, including gases, nutrients, hormones, and waste products. Vein endothelial cells also play a protective role by inhibiting the translocation of toxins or pathogens from blood to tissues. Additionally, these cells are involved in blood coagulation and inflammation response, primarily by producing substances that inhibit blood clot formation under normal conditions and initiating clotting when necessary. + +Another significant function of vein endothelial cells is the regulation of blood flow and blood pressure. They produce and release several substances, including nitric oxide and prostacyclin, which help in controlling vasodilation and vasoconstriction, thereby regulating blood pressure. These cells are also responsible for angiogenesis, the formation of new blood vessels, which is crucial during wound healing and in the formation of granulation tissue. Consequently, any dysfunction in vein endothelial cells can lead to severe health problems like atherosclerosis, hypertension, and thrombosis. +" DOI:10.1038/s41569-022-00770-1|DOI:10.1007/s00441-008-0706-5|DOI:10.3390/ijms20184411|DOI:10.1038/s41598-021-01360-w +57 CL:0002573 CL_0002573 "Schwann cells, also known as neurolemmocytes, are a type of glial cell located in the peripheral nervous system. These cells play a significant role in the healthy functioning of nerves by producing myelin, a fatty substance that forms a coating around nerve fibers. Myelin serves as an insulator and enhances the speed and efficiency of electrical nerve impulses; a single Schwann cell can myelinate a single axon. Myelination starts by the elongation and envelopment of the Schwann cell around the axon, followed by the synthesis and deposition of myelin layers. Some studies suggest that Schwann cells may regulate neuronal action potential, muscular contraction, and the sensitive response. + +While Schwann cells are most commonly known for the formation of the myelin sheath, some Schwann cells do not form myelin: Remak Schwann cells, a class of nonmyelinating Schwann cells, ensheath axons with smaller diameter, such as C fiber nociceptors in sciatic nerves and form Remak bundles. + +Schwann cells are found along both motor and sensory neurons and are crucial for the advancement and recovery of peripheral nerve injuries, due to their capacity to support nerve regeneration. In cases of nerve injury, Schwann cells play a vital role in recovery by initiating Wallerian degeneration, a process in which the part of the axon distal to the injury site degrades and is then cleared away. Following this, Schwann cells can guide the regrowth of the nerve, providing a conducive environment for axon regeneration. They remodel themselves into a regenerative phenotype, proliferate, and organize themselves into bands of Büngner that provide physical and chemical guidance for the regrowths of axons. This function of Schwann cells in the repair and regeneration of nervous system highlights their therapeutic potential in peripheral nerve injury treatments." DOI:10.1016/j.biocel.2006.05.007|DOI:10.1016/B978-0-444-52902-2.00005-9|DOI:10.1186/1742-2094-8-110|DOI:10.1002/glia.23892|DOI:10.1186/s13064-020-00140-y +58 CL:0002585 CL_0002585 "Retinal blood vessel endothelial cells constitute the innermost lining of the blood vessels found in the retina, the light-sensitive layer of tissue at the back of the eye. The primary role of these cells revolves around their location within the retinal vascular system, forming the structure of the blood-retinal barrier, a subset of the larger blood-ocular barrier system. + +The endothelial cells are particularly involved in the growth of new retinal blood vessels from pre-existing ones (angiogenesis); this is critical in managing the amount of oxygen and essential nutrients delivered to the ocular tissues. They are crucial for maintaining homeostasis in the retinal environment by controlling the exchange of molecules between the blood and the retina. Furthermore, they mediate immune cell trafficking, supporting the immune privilege of the eye by preventing the unrestricted infiltration of inflammatory cells into the retina, thus maintaining ocular health and normal vision. + +The malfunction or dysfunction of retinal blood vessel endothelial cells is implicated in numerous ocular pathologies, particularly diabetic retinopathy, which is one of the leading causes of blindness worldwide. In such conditions, the compromise in the integrity of the blood-retinal barrier and excess angiogenesis can lead to retinal edema and pathological neovascularization, resulting in vision loss. +" DOI:10.5301/EJO.2010.6049|DOI:10.1038/nature04482|DOI:10.1016/j.preteyeres.2012.08.004|DOI:0.1016/j.preteyeres.2015.08.001 +59 CL:0002618 CL_0002618 "Endothelial cells of the umbilical vein form the inner lining of the veins found in the umbilical cord. They are involved in tube formation and migration which are essential for angiogenesis, the process of generating new blood vessels; this is critical during the fetal stage for the development of the circulatory system. Endothelial cells of the umbilical vein also play a role in controlling the passage of white blood cells into tissues during inflammatory responses. + +Because human umbilical vein endothelial cells (HUVECs) can easily be derived from the umbilical cord, and because they express common endothelial cell markers, they have been used as an epithelial cell model for studies on cell proliferation, migration, angiogenesis, and inflammation. They have been used as models for vascular diseases like atherosclerosis, for investigating how tumor cells infiltrate blood vessels and form metastases. + +Thus, while endothelial cells of the umbilical vein play a critical role in vascular biology, they also represent a powerful tool in disease studies and potential treatment strategies. + +" DOI:10.1172/JCI107470|DOI:10.3390/app10030938|DOI:10.1002/cyto.a.20952|DOI:10.1007/s12015-006-0015-x|https://www.ncbi.nlm.nih.gov/books/NBK53254/ +60 CL:0002671 CL_0002671 "Endothelial stalk cells are specialized vascular cells vital in angiogenesis, a process through which new blood vessels are formed from pre-existing ones; specifically, endothelial stalk cells are involved in sprouting angiogenesis, where they help form the body of new blood vessels. + +Vascular sprouting relies on the coordinated activity of migrating endothelial tip cells at the forefront and proliferating stalk cells that elongate the sprout. The process is tightly controlled by different growths factors: Vascular Endothelial Growth Factor acts on endothelial cells, inducing them to become endothelial tip cells that initiate sprouting. After sprouting initiation, activation of Notch signaling suppresses differentiation toward a tip cell phenotype and some of the endothelial cells differentiate into stalk cells, which follow tip cells, multiply, and elongate to provide a structural backbone to the growing vessel sprout. + +In contrast to endothelial tip cells, which migrate and lead the angiogenic sprout, endothelial stalk cells behind the sprouts continue forming the tube or lumen for blood flow and facilitate maturation and stability of the new vessel. The delicate balance between the activities of stalk and tip cells during angiogenesis is crucial to build a functional vascular network. Dysfunctions in endothelial stalk cells can lead to pathological conditions such as impaired wound healing, unregulated tumor growth, and metastasis due to abnormal angiogenesis. +" DOI:10.1101/cshperspect.a006569|DOI:10.1007/s12079-019-00511-z|DOI:10.1016/j.cmet.2013.08.001|DOI:10.3389/fcell.2021.642352 +61 CL:0005009 CL_0005009 "Renal principal cells are the major cell type in the initial collecting tubule and the cortical and outer medullary collecting ducts, as well as the connecting tubule, in the nephrons of the kidneys. + +A key function of renal principal cells is the regulation of water balance in the body. These cells express aquaporin-2 (AQP2) water channels, which facilitate the reabsorption of water from the fluid within the renal tubule lumen back into the blood. The translocation of AQP2 to the cell membrane is controlled by the hormone vasopressin: In response to high vasopressin levels, AQP2 moves to the cell membrane, allowing water to pass through effectively and be reabsorbed, therefore concentrating the urine. Conversely, in low vasopressin conditions, AQP2 is removed from the membrane, reducing water reabsorption and diluting the urine. + +Renal principal cells are also involved in the regulation of sodium and potassium levels in the body. They have sodium channels (ENaC) in their luminal membranes which permit the reabsorption of sodium ions from the tubule fluid back into the blood, resulting in a net reabsorption of sodium ions into the systemic circulation. This process is controlled, in part, by the hormone aldosterone. Additionally, renal principal cells contain potassium channels that facilitate the secretion of potassium ions into the urine. The activities of these channels, in coordination with other cell types in the nephron, are critical for maintaining electrolyte balance and overall body homeostasis." DOI:10.2215/CJN.05760513|DOI:10.1016/j.krcp.2013.07.005|DOI:10.2215/CJN.08580813 +62 CL:0005011 CL_0005011 "Renal alpha-intercalated cells are located within the connecting tubules and collecting ducts of the kidneys, which are components of the kidney's complex nephron system. Along with beta-intercalated cells, they play a critical role in the body’s acid-base balance. + +Renal alpha-intercalated cells contain an abundance of proton pumps and enzymes like carbonic anhydrase, which aid in the transport of hydrogen ions for secretion in the urine. The bicarbonate/chloride transporters on their apical membrane meanwhile take up bicarbonate ions from the urine and supply them back into the blood. Through this mechanism, these cells contribute significantly to the neutrality of blood pH, and dysfunction of renal alpha-intercalated cells often leads to distal renal tubular acidosis, a condition resulting in acidic blood and alkaline urine. +" DOI:10.1152/physiol.00008.2011|DOI:10.3390/diseases2020071|DOI:10.1016/j.semnephrol.2019.04.005|DOI:10.1172/JCI63492 +63 CL:0005019 CL_0005019 "Pancreatic epsilon cells are a specialized type of endocrine cell found in the islets of Langerhans, a region of the pancreas responsible for hormone production. These clusters of cells constitute only about 1% of the pancreatic islet cell population, making them a relatively small yet significant component of the pancreas. Pancreatic epsilon cells have a round or ovoid shape with occasional cytoplasmic extensions and are characterized by small and spherical granules. + +The principal function of pancreatic epsilon cells involves the synthesis and release of the hormone ghrelin, a peptide hormone predominantly produced in the stomach; pancreatic epsilon cells are one of the few sites outside the gastrointestinal tract known to produce this hormone. Ghrelin has multiple vital roles, playing a significant part in generating hunger sensations, promoting fat storage, and influencing various metabolic processes. It also stimulates the release of Growth Hormone (GH) from the anterior pituitary gland. + +During fetal development, when they form a layer around the islet, epsilon cells are an important source of ghrelin, likely secreting the hormone into the circulation; their numbers decrease in adults. While research on pancreatic epsilon cells is still ongoing, these cells have been implicated in several disease states, most notably Type 2 diabetes and metabolic syndrome. The dysfunction or reduction in the number of pancreatic epsilon cells can lead to anomalies in ghrelin production, impacting overall metabolic homeostasis and glucose regulation. +" DOI:10.1210/en.2018-00833|DOI:10.3390/ijms20081867|DOI:10.1007/s00125-008-1238-y|DOI:10.3389/fendo.2022.904004|DOI:10.1152/physrev.00012.2004 +64 CL:0005010 CL_0005010 "Renal intercalated cells are specialized cells located in the collecting duct system of the kidneys. The primary role of intercalated cells is to reabsorb bicarbonate ions and secrete hydrogen ions, thereby maintaining the acid-base homeostasis in the blood. They comprise two main subtypes primarily distinguished by their functional and morphological attributes: alpha and beta intercalated cells. + +Alpha intercalated cells are more predominant when the body is in a state of acidosis, a condition characterized by an increased acidity of the blood. These cells are specialized in secreting excessive hydrogen ions into the urine through a mechanism involving vacuolar H+-ATPase and H+/K+-ATPase pumps on their apical membranes. They simultaneously reabsorb bicarbonate ions from the tubular fluid and return them to the bloodstream via mechanisms involving carbonic anhydrase II and bicarbonate/chloride exchangers on the basolateral membrane. This dual process helps to increase blood pH towards normal levels. + +When the body is in a state of alkalosis, a condition characterized by lowered levels of hydrogen ions in the blood, beta intercalated cells are more predominant. They primarily reabsorb hydrogen ions from the tubular fluid through vacuolar H+-ATPase and H+/K+-ATPase pumps on their basolateral membranes, while secreting bicarbonate ions into the urine via pendrin, a bicarbonate/chloride exchanger in the apical membrane. These mechanisms work together to decrease blood pH towards normal levels. + +In summary, renal intercalated cells play a critical role in the delicate balance of the body’s pH, safeguarding the body from potential harm caused by acidemia or alkalemia. +" DOI:10.2215/CJN.08880914|DOI:10.1152/ajprenal.2000.279.1.F195|DOI:10.1161/HYPERTENSIONAHA.121.16492|DOI:10.1681/ASN.V1011 +65 CL:0005026 CL_0005026 "Hepatoblasts are immature precursor cells that predominate during the early stages of liver development, specifically in the embryonic phase of life. They first arise from the endoderm, one of the three primary germ layers in the very early embryo, and then differentiate into two distinct mature liver cell types - the hepatocytes and cholangiocytes. + +During liver organogenesis hepatoblasts proliferate and migrate into the septum transversum to form the liver bud. Proliferation and differentiation of these cells are regulated by several soluble factors, such as hepatocyte growth factor, which is a mitogen of both hepatoblasts and mature hepatocytes. As they start to differentiate into hepatocytes and cholangiocytes, the cells begin to express hepatic markers like albumin and alpha-fetoprotein. + +Although hepatoblasts are specified embryonic liver cells that are bipotential for hepatocytes and cholangiocytes, a subset of liver cells (called oval cells) has been identified in adults that express stem cell markers, such as CD133 and cKIT, and has been suggested to have the same potential as hepatoblasts to differentiate into hepatocytes and cholangiocytes. +" DOI:10.1242/dev.114215|DOI:10.5966/sctm.2015-0051|DOI:10.1016/j.stem.2014.04.010|DOI:10.1093/jb/mvr001|DOI:10.1242/dev.031369 +66 CL:0008024 CL_0008024 "Pancreatic endocrine cells, as the name suggests, are found in the pancreas, specifically in the regions known as the islets of Langerhans. These cells play a pivotal role in the body's endocrine system; the range of hormones they produce regulates blood sugar levels, therefore playing a critical role in metabolism and nutrient absorption. + +The endocrine cells of the pancreas are specialized epithelial cells that are categorized based upon the type of hormone they release. Pancreatic A cells produce glucagon, a hormone that increases blood glucose levels, while type B pancreatic cells produce insulin, a hormone that reduces blood glucose levels. D cells are responsible for producing somatostatin, a hormone that inhibits the release of both insulin and glucagon. Pancreatic PP cells produce pancreatic polypeptide, a regulatory hormone that reduces pancreatic secretion and affects liver glycogen storage. Finally, epsilon cells secrete ghrelin, which regulates hunger. + +The various pancreatic endocrine cell types work synergistically to maintain the body's energy balance by regulating glucose homeostasis. Impaired function of endocrine cells is linked to medical conditions such as diabetes. In Type 1 diabetes, the immune system attacks and destroys the type B cells, resulting in an inability to produce insulin, causing elevated blood sugar levels. Conversely, in Type 2 diabetes, the body's cells become resistant to insulin, leading to an overproduction of insulin by the type B cells, eventually causing them to wear out. Thus, a deeper understanding of pancreatic endocrine cells has the potential to improve therapeutic approaches to managing and treating metabolic diseases like diabetes. +" DOI:10.1038/s41574-018-0132-z|DOI:10.1002/wdev.44|DOI:10.5402/2012/640956|DOI:10.1159/000314894|https://www.ncbi.nlm.nih.gov/books/NBK459261/#:~:text=The%20endocrine%20portion%20is%20arranged,%2C%20and%20pancreatic%20polypeptide%2C%20respectively. +67 CL:0009043 CL_0009043 "Intestinal crypt stem cells of the colon, also known as colon crypt base columnar (CBC) cells, are highly specialized cells primarily responsible for the constant self-renewal of the colonic epithelium. These cells are found in the crypts of Lieberkühn - deeply invaginated sections of the colon's mucosal layer. + +The prime function of intestinal crypt stem cells of the colon is to serve as the source of constant cell regeneration in the colon. Every few days, these stem cells divide and differentiate into the various other types of intestinal cells, such as enterocytes, goblet cells, and enteroendocrine cells. + +A constant renewal cycle is necessary due to the harsh environment of the colon where cells continuously encounter abrasive food matter and potential pathogens, leading to a high turnover rate. When the colon's mucosal layer suffers damage, a rapid response is triggered whereby colon crypt stem cells divide faster and are directed to injured sites to repair the epithelial layer. Dysregulation of these cells' function or proliferation can contribute to disorders such as colorectal cancer. + +" DOI:10.1038/s41575-018-0081-y|DOI:10.1186/s12943-019-0962-x|DOI:10.1016/j.cell.2013.07.004|DOI:10.1073/pnas.1607327113|DOI:10.1111/j.1365-2184.2009.00642.x +68 CL:0009017 CL_0009017 "Intestinal crypt stem cells of the small intestine are a type of adult stem cell intimately involved in the continuous replenishment of the intestinal epithelium, the innermost layer of the intestine responsible for nutrient absorption. These cells, located within the crypts of Lieberkühn, are the origin of various cell lineages that make up the functional units of the small intestine. They possess self-renewal ability, an essential feature of stem cells, which allows them to maintain a steady population in the small intestine. + +One of the critical roles of intestinal crypt stem cells is to drive the continual renewal process taking place in the small intestine every 3-5 days. By proliferating intensively, these cells produce transient amplifying (TA) cells that are characterized by quick division and progressive differentiation. These cells eventually differentiate into specialized cell types, encompassing absorptive enterocytes, mucin-secreting goblet cells, hormone-secreting enteroendocrine cells, and Paneth cells, all of which have essential roles in digestion and nutrient absorption in the small intestine. + +Intestinal crypt stem cells of the small intestine are also play a significant part in injury recovery. Under regular conditions, these cells primarily exist in an active state, facilitating the constant renovation of the gut lining. However, upon injury or loss of regular intestinal crypt stem cells reserve intestinal stem cells, a slow-cycling and radio-resistant population, can be stimulated to take over the duties of active crypt stem cells. Such plasticity provides a powerful regenerative mechanism that ensures the intestinal epithelium's function and structural integrity amidst diverse conditions. +" DOI:10.1038/s41575-018-0081-y|DOI:10.1073/pnas.1607327113|DOI:10.1016/j.celrep.2020.107952 +69 CL:0010003 CL_0010003 "Epithelial cells of the alveoli of the lung, also referred to as alveolar epithelial cells, play pivotal roles in gas exchange and the immune response within the respiratory system. These cells line the tiny sacs, known as alveoli, that constitute the terminal part of the bronchial tree. In a morphologically mature lung, these cells commonly appear in two phenotypic forms: type I and type II alveolar epithelial cells. + +Type I alveolar epithelial cells (AEC1s), also known as type 1 pneumocytes, provide the primary site for gas exchange between the air and the bloodstream. They have a thin, flat structure to facilitate efficient oxygen-carbon dioxide exchange, accounting for about 95% of the alveolar surface area. + +In contrast, type II alveolar epithelial cells (AEC2s), or type 2 pneumocytes, are smaller and cuboidal but play a more diversified and crucial role than their counterpart. They are active secretory cells producing surfactant, a substance that reduces alveolar surface tension, thus preventing alveolar collapse at the end of expiration and preserving lung compliance. Type II alveolar epithelial cells also have a role in regulating ion and fluid transport, which is essential for maintaining the thin layer of alveolar liquid necessary for proper gas exchange. + +Type II alveolar epithelial cells have the potential for self-renewal and serve as local progenitors for the repair and replacement of both cell types after lung injury: Type 1 alveolar epithelial cells lack the ability to self-renew, and any damage to these cells prompts type II cells to proliferate and differentiate into type I cells, thereby serving a regenerative function. +" DOI:10.1016/j.biocel.2013.08.009|DOI:10.1016/0041-008X(88)90051-8|DOI:10.1016/B978-0-12-811837-5.00012-5|DOI:10.1183/13993003.00742-2019|DOI:10.1073/pnas.0700052104 +70 CL:0011012 CL_0011012 "Neural crest cells are a group of transient and highly migratory cells that originate from the neuroectoderm during the early stages of embryonic development. They are multipotent cells with an exceptional degree of plasticity, capable of differentiating into various somatic cell types and therefore play a fundamental role in the formation of various organs and tissues, making them critical contributors to the developing embryo. + +After the initiation of neurulation (the formation of the neural tube) neural crest cells start to undergo epithelial-to-mesenchymal transition and delaminate and migrate from the dorsal neural tube to several regions throughout the embryo. They differentiate into a range of diverse cell types, such as neurons and glial cells of the peripheral nervous system, including sensory and autonomic neurons. They also contribute to the formation of adrenal glands, pigment cells in the skin (melanocytes), cardiac structures, including parts of the heart septum and major arteries, as well as bones and cartilage of the face and skull. + +Disorders or aberrations in the development or migration of the neural crest cells can lead to serious congenital malformations, such as neurocristopathies, including Hirschsprung disease, neuroblastoma, and neurofibromatosis. " https://doi.org/10.1016/j.ydbio.2011.12.042|DOI:10.3389/fcell.2020.00635/full|DOI:10.1002/dvg.23276|DOI:10.1242/dev.193193 +71 CL:1000334 CL_1000334 "Enterocytes of the epithelium of the small intestine are specialized cells that reside in the lining of the small intestine, and are primarily responsible for the essential process of nutrient absorption. These cells are columnar epithelial cells with an apical surface lined with microvilli, a feature referred to as the 'brush border', to maximize the surface area available for absorption. + +Enterocytes play a critical role in both the digestion and absorption of nutrients from food. Their extensive brush border contains enzymes that further assist in nutrient breakdown and transport proteins that transfer nutrients, such as glucose, amino acids, lipids, and vitamins, across the cell membrane. + +The enterocytes of the small intestine also participate in the barrier function of the gut lining. Enterocytes are connected by tight junctions, which act as a primary defense line against pathogenic invasion by maintaining intestinal barrier integrity. Additionally, their cell surface is coated in glycocalyx and mucus which forms a defensive barrier preventing the penetration of harmful bacteria into the systemic circulation. " DOI:10.3389/fphys.2021.699152/full|DOI:10.1084/jem.20191130|DOI:10.1038/nri3738|DOI:10.1038/nrgastro.2013.35 +72 CL:1000347 CL_1000347 "Enterocytes of the colon are specialized epithelial cells located in the lining of the colon, the largest part of the large intestine. These cells play a critical role in absorbing water, electrolytes, and certain vitamins from the food material passed on from the small intestine. With a unique structure of finger-like protrusions referred to as microvilli, the enterocytes increase their surface area for effective absorption. The colon is the last part of the digestive system, and as such, it is responsible for compacting undigested food materials and forming fecal matter. Enterocytes of the colon facilitate this process effectively through absorption of water. + +Enterocytes are known for their high regeneration potential, replenishing every 4-5 days, enabling the healthy functioning of the colon. They originate from stem cells located in the crypt of the colon and differentiate into mature enterocytes as they migrate upwards towards the luminal surface. This constant turnover aids in maintaining the intestinal barrier, preventing the entry of detrimental substances into the systemic circulation. Their tight junctions with other epithelial cells provide a robust barrier against invasive pathogens. + +Enterocytes of the colon are involved in the communication with the gut microbiota. These cells harbor enzymes necessary for the metabolism of short-chain fatty acids, which are the byproducts of the fermentation process by gut bacteria. Short-chain fatty acids serve as a major energy source for colonocytes and are important for maintaining colonic health. The dysfunction of enterocytes, therefore, could lead to disorders such as inflammatory bowel disease or colorectal cancer." DOI:10.1084/jem.20191130|DOI:10.1038/nri3738|DOI:10.1038/nrgastro.2013.35|DOI:10.3389/fimmu.2019.00277|DOI:10.1007/s11894-010-0130-3 +73 CL:1000342 CL_1000342 "Enterocytes of the epithelium proper of the ileum, commonly known as ileal enterocytes, are specialized epithelial cells found lining the inner surface of the ileum, the final section of the small intestine in the human body. They play a pivotal role in nutrient absorption, digestive metabolic functions, and the maintenance of the host’s immune response. + +Like enterocytes in other parts of the intestine, ileal enterocytes exhibit distinct characteristics specific to their function and role. They have microvilli on their apical surfaces to increase absorption and are important in the absorption of vitamins and the reabsorption of bile salts. These cells also produce enzymes that metabolize lipids and xenobiotics." DOI:10.1084/jem.20191130|DOI:10.1038/nri3738|DOI:10.1111/j.1365-2249.2011.04523.x +74 CL:1000436 CL_1000436 "Epithelial cells of the lacrimal sac play a significant role in the physiology of tear drainage, acting as an integral part of the lacrimal drainage system. The lacrimal sac is part of the nasolacrimal duct system, a conduit which connects the eye to the nasal cavity, and is lined by multilayered, non-keratinizing, squamous epithelial cells. + +The epithelial cells of the lacrimal sac are specialized for the purpose of maintaining a moist environment and protecting the surface of the eye. They form a barrier that traps and removes potential contaminants from the tear film during the drainage process. These cells also actively contribute to tear turnover by expediting the drainage of excess tears. Dysfunctional epithelial cells of the lacrimal sac can lead to dacryocystitis, a condition characterized by inflammation of the lacrimal sac. + +Epithelial cells of the lacrimal sac also perform various other tasks which ensure the overall health of the eye. They are involved in the regulation of immune responses within the lacrimal apparatus and may have a possible role in host-microbiome interactions. Thus, epithelial cells of the lacrimal sac play a multifaceted role in tear drainage and ocular surface defence, directly translating to eye health and vision quality. +" DOI:10.1007/s004290050160|DOI:10.2147/OPTH.S26048|DOI:10.1111/j.1442-9071.2012.02818.x|DOI:10.1167/tvst.8.4.32|DOI:10.3389/fimmu.2022.918619 +75 CL:1000413 CL_1000413 "Endothelial cells of the artery, also referred to as arterial endothelial cells, form an integral part of the arterial system. They form a single layer, known as the endothelium, lining the interior surface of arteries, and are able to respond to the high-pressure and flow conditions present in arteries. The primary role of these cells is to provide a barrier between the vessel wall and the blood, exhibiting selective permeability to regulate the movement of liquids, gases, and blood-borne substances across the vascular wall. + +Arterial endothelial cells significantly contribute to maintaining vascular homeostasis. They are at the forefront of sensations and responses to mechanical stimuli, like shear stress and blood pressure changes. An additional key function pertains to the production of nitric oxide, which helps to regulate vascular tone and blood pressure, prevents platelet aggregation, limits leukocyte adhesion to the endothelium, and inhibits smooth muscle cell proliferation. These varied but connected functions help to preclude the development of atherosclerosis, ensuring normal circulation and arterial health. + +Moreover, these cells play a pivotal role in inflammation and coagulation processes. During inflammatory events, they express various adhesion molecules, aiding in leukocyte recruitment and rolling onto the vessel walls for immune response. They also produce anticoagulant and procoagulant substances, involved in blood clotting and clot dissolution, respectively. Dysregulation of the usual functions of arterial endothelial cells can result in serious pathophysiological conditions, such as atherosclerosis, hypertension, and other cardiovascular diseases. +" DOI:10.1007/s10456-021-09785-7|DOI:10.1016/j.ccm.2021.08.005|DOI:10.1007/s00441-008-0706-5|DOI:10.1177/153857440303700107|DOI:10.1016/j.jvs.2004.03.043 +76 CL:1000454 CL_1000454 "Kidney collecting duct epithelial cells are a specialized type of cells that form an integral part of the renal system. Located in the collecting duct system of the kidneys, these cells are responsible for one of the final steps in the process of urine formation, and they are instrumental in the fine tuning of the volume and composition of urine by reabsorbing water and certain solutes back into the bloodstream. + +These cells express specific channels and carriers that actively and passively transport ions and water. They also have channels on their membranes, such as sodium channels and potassium channels, involved in reabsorbing or secreting these electrolytes depending upon the body's needs. The function of renal collecting duct epithelial cells can be regulated by a variety of hormones, including vasopressin (antidiuretic hormone), which can modulate the ion channels and carriers and hence indirectly influence body fluid homeostasis. + +Aside from their function in ion and water balance, kidney collecting duct epithelial cells also aid in maintaining the body's acid-base balance. They have specialized functionality to secret hydrogen ions into the tubular lumen, which contributes to acid excretion. Any dysfunction may have serious implications and lead to various renal or systemic diseases, exemplifying the importance of these cells in maintaining overall body homeostasis. +" DOI:10.2215/CJN.08880914|DOI:10.2215/CJN.05760513|DOI:10.1016/j.semnephrol.2019.04.005|DOI:10.1016/j.ajpath.2014.01.014 +77 CL:1000488 CL_1000488 "Cholangiocytes, also known as biliary epithelial cells, are specialized epithelial cells that line the biliary tract, which constitutes the gall bladder and bile ducts inside the liver. Crucial to the maintenance of the liver's health and function, cholangiocytes have a key role in the modification and secretion of bile, a fluid produced by hepatocytes that is essential to digestion and the absorption of fats and vitamins. + +Cholangiocytes accomplish their primary function through the expression of a variety of transport proteins located on their apical and basolateral membranes, which propel bile acids and other contents of the bile into the biliary lumen. The hepatic bile, once secreted by the hepatocytes, is further modified by cholangiocytes via secretion and absorption processes. These processes help in the regulation of bile volume and composition, which is fundamental in ensuring the efficient digestion of dietary fats and fat-soluble vitamins and the excretion of cholesterol. + +In addition to their role in bile modification, cholangiocytes also perform several other integral functions. For instance, these cells express Toll-like receptors (TLRs) which allow cholangiocytes to initiate an immune response against pathogens in the biliary lumen. When functioning normally, these cells contribute to biliary integrity, hepatic architecture, and overall hepatic physiology. However, when they become pathological, they are involved in the progression of liver diseases, such as primary biliary cirrhosis and cholangiocarcinoma – the malignancy of the biliary tract. +" DOI:10.1038/s41575-019-0125-y|DOI:10.1016/j.jcmgh.2015.05.005|DOI:10.1016/j.jhep.2012.10.011|DOI:10.1152/ajpgi.00227.2012|DOI:10.5009/gnl16033 +78 CL:1000493 CL_1000493 "Mesothelial cells of visceral pleura are specialized epithelial cells that line the inner layer of the pleura, the membrane that envelops the lungs. Positioned adjacent to the lung tissue, these cells form a protective barrier and contribute to the structure of the visceral pleura. They are characterized by their cuboidal to squamous epithelial shape and the presence of microvilli on their surface, a feature aiding in fluid and solute exchange between the pleura and the lungs. + +The primary function of mesothelial cells of visceral pleura is to secrete a lubricating serous fluid to facilitate smooth, frictionless lung movement within the thoracic cavity during respiration. This helps in the prevention of trauma or damage stemming from the constant rubbing of the lung tissue against the chest wall, hence playing a pivotal role in maintaining respiratory function. Besides fluid secretion, these cells have an essential role in the transportation of fluids and particles across the pleura, as well as in inflammation, wound healing, and tissue repair processes within the pleura. + +Mesothelial cells of visceral pleura are notably implicated in the development of pleural diseases such as pleural effusion and pleural mesothelioma, a rare and aggressive form of cancer primarily linked with exposure to asbestos. Alterations, such as hyperplasia or metaplasia, may occur in these mesothelial cells under pathological conditions. +" DOI:10.1016/S1357-2725(03)00242-5|DOI:10.3390/jdb7020007|DOI:10.1152/physrev.00026.2003|DOI:10.1371/journal.pone.0276978|DOI:10.3389/fphys.2014.00221 +79 CL:1000491 CL_1000491 "Mesothelial cells of the pleura form a significant part of the pleural membrane, a thin, double-layered serous membrane that lines the thoracic cavity and encompasses the lungs. These specialized cells contribute to the pleura's key function of producing a lubricating serous fluid, which reduces friction between the lung's outer surface (visceral pleura) and the inner lining of the thoracic cavity (parietal pleura) during respiration. + +The cellular structure of mesothelial cells, characterized by microvilli on their surface, aids in the secretion and absorption of the pleural fluid, effectively supporting the smooth expansion and contraction of the lungs. Dysregulation in mesothelial cells can lead to pathologies, including pleural effusion and malignant mesothelioma. + +Mesothelial cells of the pleura display unique immunologic properties. They act as a first line of defense against infection because they are able to recognize pathogens and respond by secreting various cytokines and chemokines. Additionally, these cells are directly involved in the translocation of immune cells into the pleural cavity during inflammatory response, thereby playing an active role in the immune response within the pleural environment. + +In the event of pleural injury, these cells are also involved in the mesothelial-mesenchymal transition, a process that allows mesothelial cells to transdifferentiate into myofibroblasts and promote tissue repair. +" DOI:10.1016/j.ccm.2021.08.005|DOI:10.1152/ajplung.90587.2008|DOI:10.1016/j.coi.2020.04.005|DOI:10.3389/fphys.2014.00284 +80 CL:1000892 CL_1000892 "Kidney capillary endothelial cells form the innermost lining of the capillaries and microvessels within kidneys, including those lining the glomerular capillaries and the vasa recta. Each cell exhibits a unique array of adhesion molecules, receptors, and secreted mediators which interact with circulating blood cells and solutes. + +One of the key functions of kidney capillary endothelial cells is enabling filtration, reabsorption, secretion, and excretion – the crucial steps in the formation of urine. In the glomerulus, these cells form a collaborative relationship with the podocytes to constitute the glomerular filtration barrier; here, the ultra-thin endothelial cells create a wall through which water and small solutes pass while retaining larger proteins and molecules within the bloodstream. This permits the rapid and selective filtration of plasma, a primary aspect of the kidney's role in waste clearance and fluid, electrolyte, and acid-base homeostasis. + +Kidney capillary endothelial cells also conduct multiple homeostatic roles, such as vasomotor control, fibrinolysis, platelet adhesion, inflammation, and coagulation. They also play a crucial role in responding to renal injury by participating in fibrogenesis, an initial response following acute kidney injury. The endothelial cells spearhead angiogenesis (new blood vessel formation) and the repair and regeneration of renal tissue, thereby enhancing the survival function of the kidney itself. Furthermore, factors secreted by kidney capillary endothelial cells also help control the growth and differentiation of other types of renal cells. +" DOI:10.1016/j.biocel.2010.05.015|DOI:10.1038/sj.ki.5002312|DOI:10.1111/j.1523-1755.2005.00260.x|DOI:10.1038/s41581-021-00411-9 +81 CL:1001005 CL_1001005 "The glomerular capillary endothelial cell comprises an intrinsic component of the glomerulus in the kidney. Glomeruli contain a network of capillaries where the first step of blood filtration takes place, with glomerular capillary endothelial cells acting as an integral part of this process. Unlike regular endothelial cells that line the vasculature, unique fenestrations (openings) characterize these cells, allowing for enhanced permeability and filtration efficacy. + +Together with the glomerular basement membrane and podocytes, the glomerular endothelial cells form the glomerular filtration barrier, which is responsible for blood filtration and therefore critical for removal of waste products, such as urea and creatinine, and excess substances, such as glucose and ions, from the bloodstream. The glomerular capillary endothelial cells' fenestrations permit the free flow of a variety of particles, barring larger, negatively charged proteins like serum albumin, enabling the formation of an ultrafiltrate. This ultrafiltrate is the primitive form of urine, which then passes through the proximal tubule for further processing and ultimately helps maintain systemic fluid and electrolyte balance. + +Moreover, the glomerular capillary endothelial cells are also believed to play a crucial role in renal pathologies. Any compromise to their structural integrity or functional performance can lead to kidney diseases, including but not limited to, diabetic nephropathy and glomerulonephritis. For instance, in diabetes, persistent hyperglycemia can injure these cells, leading to a compromised glomerular filtration barrier and proteinuria, indicating the loss of proteins in the urine. + + + +" DOI:10.1016/j.biocel.2010.05.015|DOI:10.1111/j.1523-1755.2005.00260.x|DOI:10.2337/diacare.28.1.164|DOI:10.3389/fphys.2021.689083|DOI:10.1016/j.yexcr.2012.02.032 +82 CL:1001099 CL_1001099 "Kidney efferent arteriole endothelial cells constitute a vital component of the kidney's microvascular system. They are unique endothelial cells found lining the walls of efferent arterioles, which transport blood away from the glomeruli in the kidney. + +The primary responsibilities of the kidney efferent arteriole endothelial cells involve controling renal blood flow, regulating glomerular filtration rate (GFR), and managing perfusion pressure. They do this by contracting and relaxing, effectively narrowing and widening the arteriole's lumen thereby controling the volume and rate of blood flow to the peritubular capillaries and creating the pressure gradient necessary for filtration in the glomerulus. + +Furthermore, kidney efferent arteriole endothelial cells show a high degree of plasticity in response to pathophysiological stimuli and can undergo structural and functional changes based on local needs. In conditions like hypertension and diabetes, these cells can experience hypertrophy and endothelial dysfunction, contributing to the progression of renal disease. + " DOI:10.1016/j.semcdb.2014.08.002|DOI:10.1681/ASN.2019111179|DOI:10.1016/j.semnephrol.2015.01.010|DOI:10.1038/s41581-021-00411-9 +83 CL:1001096 CL_1001096 "Kidney afferent arteriole endothelial cells are a specialized type of cell located within the kidneys, forming the inner lining of the afferent arterioles, which are responsible for delivering blood to the glomeruli - capillary networks responsible for filtration - from where the process of urine formation begins in the nephrons. + +The endothelial cells in the kidney afferent arterioles have a key function in regulating the blood flow and filtration. They have autocrine and paracrine signaling capabilities, meaning they can signal to themselves and other nearby cells. They produce nitric oxide, prostacyclin, and endothelin, which are powerful vasodilators and vasoconstrictors that regulate renal blood flow. These cells also engage in the mitigation of kidney injury and inflammation by promoting repair and regeneration, demonstrating the multifaceted roles these cells play in maintaining renal health. +" DOI:10.1093/ndt/gfl308|DOI:10.1046/j.0001-6772.2003.01205.x +84 CL:1001131 CL_1001131 "The vasa recta ascending limb cells are specialized epithelial cells that are part of the vasa recta in the kidney, a crucial component of the renal medulla that functions as a counter-current exchanger to maintain the concentration gradient required for water reabsorption. These particular cells are located in the ascending limb of the vasa recta, which takes blood flow from the medulla back to the cortex. + +The primary function of vasa recta ascending limb cells is to preserve the renal medulla's hypertonicity, necessary for the kidney's urine concentration mechanism. Unlike the vasa recta descending limb cells, the venous-like epithelial cells of the ascending vasa recta are highly fenestrated and lack pericyte coverage, which facilitates water reuptake. +As the blood flows through the ascending limb, it loses solutes and gains water, which is driven by the high solute concentration in the surrounding interstitium. This process acts in concert with cellular action in the descending limb and contributions from the so-called Loop of Henle, which helps with water and sodium chloride retrieval from the urine. + +In the context of normal physiological processes, the function of the vasa recta ascending limb cells is essential in maintaining the body's overall fluid balance, electrolyte concentration, and systemic blood pressure. Any dysfunction in these cells may lead to impaired urine concentration or dilution capability of the kidney, potentially resulting in conditions like diabetes insipidus or hyponatremia. +" DOI:10.1152/ajpregu.00657.2002|DOI:10.1111/apha.12026|DOI:10.1053/j.ajkd.2005.01.008|DOI:10.1081/jdi-100101958|DOI:10.1016/B978-0-323-35515-5.00009-9 +85 CL:1001285 CL_1001285 "Vasa recta descending limb cells are specialized epithelial cells found in the vasa recta, a network of blood vessels in the renal medulla. These cells line the interior surface of the descending limb of the vasa recta and play a crucial role in the filtering and regulation of substances within the blood. + +In contrast to vasa recta ascending limb cells, the arterial-like epithelial cells of the descending vasa recta are non-fenestrated and covered by a pericyte layer that regulates the medullary blood flow. They help keeping the body’s fluid and electrolyte balance in check through a process known as countercurrent exchange system, in which the cells of the descending limb are permeable to water but relatively impermeable to solutes, such as sodium and urea. As the blood descends into the medulla along its descending limb, water passively diffuses out of the vasa recta, concentrating the blood in solutes. + +In addition to their central role in water and solute exchange, these cells contribute to maintaining the medullary osmotic gradient, a critical function to concentrate urine. The osmotic gradient is created by the counterflow of water and solutes between the descending and ascending limbs of the vasa recta and the adjacent Loop of Henle. The selective permeability of the descending limb cells allows them to maintain this gradient, which in turn helps to conserve water, a vital role in the overall function of the renal system. Thus, vasa recta descending limb cells have a significant function in renal physiology, particularly in osmoregulation and fluid balance. + +" DOI:10.1152/ajpregu.00657.2002|DOI:10.1111/apha.12026#apha12026-bib-0039|DOI:10.1053/j.ajkd.2005.01.008|DOI:10.1081/jdi-100101958 +86 CL:1001431 CL_1001431 "The kidney collecting duct principal cell is a highly specialized type of cell found in the late distal convoluted tubule and collecting duct of the kidney's nephron. Principal cells are located at the final segments of the renal tubules, where they play a pivotal role in key homeostatic processes. + +One of their fundamental functions of kidney collecting duct principal cells is the regulation of water reabsorption, which is mediated by aquaporins (water channel proteins). Antidiuretic hormones, such as vasopressin, can stimulate the redistribution of these water channels from an intracellular pools to the apical plasma membrane of the principal cell; translocation of aquaporin (specifically, AQP2) is associated with an increase of osmotic water permeability. The water reabsorption affects the concentration of the final urine; these cells are therefore directly involved in the maintenance of the body's fluid balance. + +Kidney collecting duct principal cells also participate in sodium and potassium ions regulation. They reabsorb sodium ions from the tubular fluid back into the bloodstream, a process facilitated by the action of aldosterone, a hormone released by the adrenal glands. Similarly, the principal cells secrete potassium ions into the tubular fluid in response to aldosterone, contributing to the regulation of potassium levels in the body. Impaired function of cells can lead to various renal diseases and disorders, highlighting the vital role of kidney collecting duct principal cells in the body's homeostatic processes. +" DOI:10.1016/B978-0-12-386456-7.05402-2|DOI:10.1073/pnas.1710964114|DOI:10.1007/s11906-015-0538-0|DOI:10.1016/j.biocel.2022.106261 +87 CL:1001567 CL_1001567 "Lung endothelial cells form a vital part of the lung vasculature, which includes arteries, capillaries, and veins. These specialized epithelial cells of the lung line the entire circulatory system, serving as a highly selective barrier between the circulating blood and the tissues, and playing a crucial role in governing the exchange of oxygen and carbon dioxide. Furthermore, endothelial cells are remarkably heterogeneous, with lung endothelial cells being distinctly different from endothelial cells found in other organs, highlighting their highly specific role and the importance of the local tissue environment. + +Lung endothelial cells play key roles in several physiological processes, such as blood clotting, inflammation, vasomotor control, and vascular permeability. By rapidly responding to various factors, these cells can modulate the diameter of blood vessels and control blood flow to different regions of the lung. They exhibit unique permeability properties that permit the transfer of nutrients, hormones, gases, and cells between the bloodstream and the lung parenchymal tissue. + +Moreover, lung endothelial cells play a significant role in disease states, including lung injury, inflammation, pulmonary hypertension, and tumorigenesis. They are known to respond to injury by altering their barrier properties, secreting inflammatory mediators, and expressing adhesion molecules, all of which contribute to tissue inflammation and repair. +In pulmonary hypertension, changes in lung endothelial cell function play a role in the pathological constriction and remodeling of blood vessels. Likewise, in lung cancer, these cells contribute to tumor growth and metastasis through angiogenesis. +" DOI:10.7554/eLife.53072|DOI:10.3389/fphys.2022.976873|DOI:10.1136/thoraxjnl-2015-207461|DOI:10.1186/1465-9921-10-95|DOI:10.1183/13993003.00745-2017 +88 CL:1001597 CL_1001597 "Seminal vesicle glandular cells belong to a specialized group of epithelial cells that form the internal lining of the seminal vesicles, a pair of male reproductive organs. These cells are located within the complex tubuloalveolar glands that make up the seminal vesicles and are known for their unique pseudostratified columnar epithelium structure. + +The primary function of these cells is the secretion of a variety of substances that ultimately constitute around 70% of the fluid volume of semen. Seminal cells produce a high-fructose fluid that serves as an energy source for the spermatozoa and promotes their motility. They also secrete other essential substances like proteins, enzymes, vitamin C, prostaglandins, and various other compounds. Collectively, these substances help in the nourishment, protection, and transportation of the spermatozoa throughout the male reproductive system and during the ejaculation process. + +Secondary to the production of seminal fluid, the seminal vesicle glandular cells also play a role in the contraction of the seminal vesicles during ejaculation. The contraction of these glands, induced by sympathetic nerves, ensures the efficient propulsion of the seminal fluid mixed with spermatozoa into the ejaculatory ducts and subsequently to the urethra. Notably, any malfunction or pathological condition affecting these cells can impact male fertility, emphasizing the importance of understanding the intricate functions of seminal vesicle glandular cells in maintaining the healthy physiological function of male reproduction. +" DOI:10.1111/j.1439-0272.1992.tb02636.x|DOI:10.1007/s00265-006-0178-0|DOI:10.1007/978-3-030-32300-4_26|https://www.ncbi.nlm.nih.gov/books/NBK499854/|https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/seminal-vesicle +89 CL:2000016 CL_2000016 "Lung microvascular endothelial cells form the inner lining of the microvascular system in the lungs, a network of tiny blood vessels that facilitates the exchange of gases between the bloodstream and the pulmonary air spaces. + +Pulmonary microvascular endothelial cells are important not only in optimizing gas exchange and controling barrier integrity and function, but also in regulating pulmonary vascular tone. By regulating vascular tone, these cells contribute to the maintenance of lung function and structure; they ensure the proper supply of oxygen and nutrients to help tissues remain healthy and maintain their essential functions. They also act as interfaces between circulating blood and tissues, managing the trafficking of inflammatory and immune cells. + +Pulmonary microvascular endothelial cells differ from their macrovascular counterparts in several structural ways, including glycocalyx structure, ion channel expression and function, and the organization of signal transduction networks. Pulmonary microvascular endothelial cells are also different in their function as they form a tighter barrier and show less permeability to sucrose and albumin than macrovascular endothelial cells. + +Derangement of this barrier increases vascular permeability and contributes to the hypoxemia associated with adult respiratory distress syndrome and noncardiogenic pulmonary edema. +" DOI:10.1513/pats.201101-004MW|DOI:10.3389/fbioe.2020.00105|DOI:10.1016/j.mvr.2004.02.002|DOI:10.1513/pats.200803-027HR?journalCode=pats|DOI:10.1152/ajplung.1998.274.5.L810 +90 CL:2000018 CL_2000018 "Endothelial cells of the coronary artery are specialized cells that line the inner surface of the coronary arteries, which supply oxygen-rich blood to the myocardium (heart muscle). These cells play key roles in vascular biology including the regulation of vascular tone, blood coagulation, leukocyte adhesion, and platelet adhesion. They are also responsible for maintaining the integrity of the vascular wall. + +To maintain cardiovascular homeostasis, the endothelial cells of the coronary artery produce substances such as endothelin, a powerful vasoconstrictor, and prostacyclin, which has vasodilatory, anti-inflammatory, and anti-thrombotic properties. They also produce nitric oxide, which has a protective role in the vasculature, preventing inflammation, thrombosis, and platelet aggregation, which are major risk factors for atherosclerosis, leading to coronary heart disease. + +Dysfunction or impairment of endothelial cell function in coronary arteries is often considered an early prognostic marker in the development of atherosclerosis. With decreased nitric oxide production or availability, the arterial wall becomes more prone to inflammation, thrombosis, and constriction, all of which lead to plaque formation and eventual blockage of the artery. +" DOI:10.1055/s-0031-1283220|DOI:10.1097/00041433-200108000-00003|DOI:10.1097/MCA.0000000000000178|DOI:10.1161/01.CIR.0000153339.27064.14 +91 CL:2000059 CL_2000059 "Prostate gland microvascular endothelial cells are located in the microvasculature, the smallest blood vessels, of the prostate gland. These cells play a vital role in homeostatic functions including regulation of blood flow, vascular permeability, coagulation, and inflammation. They form the delicate inner lining (endothelium) of the microvessels, thereby facilitating transfer of materials between the blood and the prostate tissue. + +These endothelial cells are involved in various multifaceted cellular processes. They aid in the formation of new blood vessels from pre-existing ones (angiogenesis), allowing for the adequate supply of nutrients. Furthermore, these cells contribute significantly to the prostate gland's immune response capability. They express several adhesion molecules which play a critical role in guiding immune cells, such as leukocytes, to areas of inflammation or injury in the prostate gland. + +Abnormal function or behavior of microvascular endothelial cells has been associated with pathological conditions, such as prostate cancer. In malignancy, these cells facilitate the growth and spread of cancer cells by creating new blood vessels (tumor angiogenesis); anti-angiogenic therapeutic strategies in prostate cancer have targeted these cells, focused on inhibiting new blood vessel formation. +" DOI:10.1111/j.1464-410X.2012.11444.x|DOI:10.1016/j.critrevonc.2013.01.002 +92 CL:0002250 CL_0002250 "Intestinal crypt stem cells, also known as crypt base columnar cells, are a unique type of cell, characterized by the highly specific marker LGR5, found in the intestinal epithelium. Situated at the bottom of the minute pockets known as crypts of Lieberkühn, these are undifferentiated cells that have the ability to perpetually self-renew, as well as differentiate into various other cell types that constitute the epithelial lining of the intestine. + +The fundamental role of intestinal crypt stem cells is to provide a constant supply of new cells to maintain the cellular turnover of the intestinal epithelium, a tissue known for rapid self-renewal. These stem cells are nurtured and protected by specialized epithelial and mesenchymal cells, and together constitute the intestinal stem cell niche. + +An important function of intestinal crypt stem cells is to sustain the balance between cell division and programmed cell death, called apoptosis, to ensure the integrity of the intestinal lining. Given their active proliferation rate, these stem cells initiate the creation of diverse differentiated cell types, including enterocytes (the primary absorptive cells in the intestinal lumen), goblet cells (that produce mucus to protect the epithelial layer), enteroendocrine cells (involved in producing gastrointestinal hormones), and Paneth cells (involved in secreting antimicrobial peptides). This diversity in output regulates the physiological activities of the gut ranging from nutrient absorption, hormone secretion, bacterial balance, to immunity. + +Research studies suggest that dysregulation in intestinal crypt stem cell proliferation and differentiation is associated with several intestinal disorders including intestinal cancer, and various enteropathies. +" DOI:10.1111/j.1365-2184.2009.00642.x|DOI:10.1038/s41575-018-0081-y|DOI:10.1016/j.cell.2013.07.004|DOI:10.1101/gad.1674008|DOI:10.1038/s41580-020-0278-0 +93 CL:0002275 CL_0002275 "Pancreatic polypeptide (PP) cells (also called F or gamma cells) are unique endocrine cells located within the Islets of Langerhans in the pancreas. PP cells are one of the rarer pancreatic cell types and are more prevalent in the head and neck of the pancreas. They are critical in normal pancreatic physiological functions and are involved in the development of pancreatic endocrine disorders. + +The primary function of PP cells is the production and secretion of the pancreatic polypeptide hormone (PP). This hormone plays a crucial role in several gastrointestinal functions and metabolic responses. The release of the PP hormone is stimulated after eating, especially in protein-rich meals, leading to it being present in large amounts during digestion. The fundamental role of PP is to self-regulate pancreatic secretion activities ensuring its exocrine and endocrine functions are under control. + +The pancreatic polypeptide hormone from PP cells also aids in adapting to low physical activity and fasting by reducing the production of insulin and glucagon and inhibiting the hepatic glucose production. Additionally, this hormone influences gut motility by slowing down the gastric emptying and reducing small intestinal transit, thereby controlling the pace at which nutritional substances are absorbed. Because of these functions, any malfunction or irregularity in PP cells can result in various disorders such as diabetes and pancreatic diseases. +" DOI:10.1038/s42255-019-0148-2|DOI:10.1016/B978-012369442-3/50154-9|DOI:10.3389/fendo.2023.1192311|DOI:10.1016/j.mce.2015.06.028|DOI:10.1016/B978-0-12-819402-7.00001-2 +94 CL:0002303 CL_0002303 "Pigmented ciliary epithelial cells, which are a type of pigment cell, have a crucial function within the eye's ciliary body. The ciliary body, located behind the iris, is one of the eye’s most vital structures and consists of two types of epithelial cells: the pigmented and the non-pigmented ciliary epithelial cells. The pigmented ciliary epithelial cells form the outer layer of the ciliary body and exhibit a black or brown pigmentation due to the melanin they contain. + +One key function of pigmented ciliary epithelial cells is to aid in the formation of aqueous humor, an intraocular fluid that nourishes the cornea and lens, and maintains intraocular pressure which is essential for the eye’s shape and light refraction. These cells facilitate this function in conjunction with the non-pigmented ciliary epithelial cells. Together, the pigmented and non-pigmented ciliary epithelial cells form a bilayer epithelium that allows the secretion of aqueous humor through a bi-directional fluid transport mechanism. + +Pigmented ciliary epithelial cells also contribute to the blood-aqueous barrier, a physiological frontier that controls the entry and exit of various substances from the blood to the aqueous humor and vice versa. The pigmentation in these cells, intensified by melanin, helps to absorb scattered light coming into the eye, reducing any potential damage and glare. +" DOI:10.1016/S1569-2590(05)10005-6|DOI:10.1111/j.1444-0938.2002.tb02384.x +95 CL:0002304 CL_0002304 "Non-pigmented ciliary epithelial cells are a specialized cell type found in the ciliary body of the eye. The ciliary body is responsible for producing the aqueous humor, which is the clear, watery fluid that fills the anterior portion of the eye. These cells, also known as the ciliary epithelium's non-pigmented layer, are located immediately beneath the pigmented ciliary epithelial cells. They play several key roles in maintaining eye health and function and contribute to the eye's intricate physiology. + +Together with the endothelial cells of the iris and ciliary blood vessels, the non-pigmented ciliary epithelium form the blood aqueous barrier in the anterior part of the eye. One of the main functions of non-pigmented ciliary epithelial cells includes the production and regulation of aqueous humor, which provides nourishment and oxygen supply to the avascular lens and cornea, two vital eye components found in the anterior segment. Aqueous humor also helps to maintain intraocular pressure, which is critical for retaining the shape of the eye. Aberrations in this balance often result in ocular pathologies like glaucoma. Non-pigmented ciliary epithelial cells play a key role in the secretory processes that regulate the aqueous humor through active transport, diffusion, and ultrafiltration from the blood plasma. + +Therefore, due to their complex and multi-faceted functions sustaining eye health, non-pigmented ciliary epithelial cells represent a critical cell type in eye biology and physiological equilibrium. +" DOI:10.1016/S1569-2590(05)10005-6|DOI:10.1007/978-1-4615-1203-5_15 +96 CL:4023181 CL_4023181 "Hypendymal cells are secretory cells located between the ependymal layer and the posterior commissure, forming the hypendmal layer of the subcommissural organ (SCO), a highly conserved gland that is part of the circumventricular system within the brain. + +Hypendymal cells are bipolar cells with a thin apical pole and basal process. Most of the ultrastructural characteristics of these cells are similar to those described for the ependymal cells (which are arranged into another layer – the ependyma). However, ependymal cells release their secretion into the ventricular cerebrospinal fluid whereas hypendymal cells project processes to the local blood vessels and to the subarachnoidal space. + +" DOI:10.1111/joa.13709|DOI:10.1002/(SICI)1097-0029(19980415)41:2<98::AID-JEMT2>3.0.CO;2-M|DOI:10.3389/fncel.2015.00480 +97 CL:0017000 CL_0017000 "The pulmonary ionocyte is a relatively newly identified, specific epithelial cell type found primarily in the pulmonary or respiratory system. Discovered through novel mapping techniques in 2018, these cells are surprisingly rare, making up less than 2% of the cells in the lung's airway, yet they play an essential role in the airway surface liquid and mucus regulation, a crucial factor in lung health. + +The main responsibility of the pulmonary ionocyte pertains to the regulation and mobilization of chloride ions. They express a high level of CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene, which encodes a protein channel across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes. The activity of CFTR regulates the movement of chloride ions and fluids in and out of cells, which helps maintain a balance of fluid in the organs they are expressed in. If CFTR is dysfunctional, it can cause conditions such as cystic fibrosis, characterized by thick, sticky mucus that can clog the lungs and obstruct the pancreas, leading to respiratory and digestive issues. + +The discovery of this cell type offers new doors to the treatment and further understanding of diseases like cystic fibrosis. Increased understanding of pulmonary ionocytes could contribute to the development of novel therapeutic approaches to manipulate the function of CFTR in the lungs and other organs affected by dysfunctional CFTR. +" DOI:10.1038/s41586-018-0393-7|DOI:10.1146/annurev-pathol-042420-094031|DOI:10.1172/JCI171268 +98 CL:1000143 CL_1000143 "Lung goblet cells are critical components of the respiratory tract, specifically found in the bronchial segments. They are secretory epithelial cells known for their signature ""goblet"" or cup-like shape. Their primary function is to produce and secrete mucus that aids in trapping airborne particles and pathogens, preventing them from reaching the delicate environment of the lung. As part of the lung's epithelial lining, they act as frontline defenders, maintaining lung health and function. + +The lung goblet cells are densely packed with granules containing mucin glycoproteins, the primary component of mucus. As mucus is produced and secreted, it moves towards the lumen of the lungs where the cilia, hair-like structures of the neighboring ciliated epithelial cells, help to navigate it upwards and out of the respiratory tract. This coordinated action ensures the expulsion of unwanted particles and pathogens, effectively cleaning the respiratory tract. + +Dysfunction or abnormal proliferation of lung goblet cells can result in pathological conditions such as chronic obstructive pulmonary disorder (COPD) and asthma, where excessive mucus production leads to airway obstruction. Furthermore, lung goblet cells respond to a variety of stimuli, including toxins, allergens, irritants, and infections, adjusting their mucus production accordingly. +" https://www.ncbi.nlm.nih.gov/books/NBK553208/|DOI:10.1038/s41385-020-00370-7|DOI:10.1038/s41385-018-0039-y|DOI:10.1513/AnnalsATS.201802-128AW |DOI:10.1159/000512268 +99 CL:1000223 CL_1000223 "Lung neuroendocrine cells, also commonly known as pulmonary neuroendocrine cells (PNECs), are predominantly located in the respiratory epithelium of the bronchial and bronchiolar airways in the lungs. These cells, characterised by their small size and granular appearance, have a distinctive morphology that sets them apart from other lung cells. They are considered part of the diffuse neuroendocrine system due to their scattered distribution through the epithelium and have been classified into solitary cells and clustered forms known as neuroepithelial bodies. + +The primary function of PNECs is linked to regulation and maintenance of the lung environment. They are sensory in nature and can secrete various bioactive substances such as serotonin, calcitonin, calcitonin gene-related peptides, and bombesin-like peptides which modulate airway smooth muscle tone and influence gut motility. For example, they act as oxygen sensors in response to hypoxia and are responsible for releasing neuropeptides that can induce responses. Moreover, PNECs provide an afferent function as they are equipped with long microvilli that project into the lumen of the bronchus and react to changes in the chemical composition of the luminal content. +" DOI:10.1016/j.devcel.2020.09.024|DOI:10.1016/bs.ctdb.2018.12.002|DOI:10.1242/dmm.046920 +100 CL:0000166 CL_0000166 "Chromaffin cells, also known as pheochromocytes, are neuroendocrine cells that are typically located in the adrenal medulla, the innermost part of the adrenal gland, which is situated on top of each kidney. Chromaffin cells are also found in small clusters, known as paraganglia, in various locations throughout the body, including the sympathetic nervous system. They derive their name from their ability to stain a brownish-black color upon exposure to chromic salts, a feature made possible due to their high content of granules rich in catecholamines and catecholamine-related neurotransmitters. + +The primary function of chromaffin cells is the synthesis and release of catecholamines, specifically epinephrine (adrenaline) and norepinephrine (noradrenaline). These neurotransmitters are vital stress hormones that, when released by the adrenal chromaffing cells into the bloodstream, prepare the body for the 'fight or flight' response. This response can enhance the body's performance in a dangerous situation by increasing heart rate, elevating blood sugar, and increasing blood flow to the muscles. The chromaffin cells in paraganglia are responsible for the local release of catecholamines and play a role in regulating blood pressure and other autonomic functions. + +In addition to their role in stress response, chromaffin cells also contribute to the body's immune response. They secrete several peptides including antimicrobial peptides, and the discovery of LPS and cytokine receptors on chromaffin cells suggests that the adrenal medulla may participate in some aspects of the immune response. + +" DOI:10.1002/cphy.c190003|DOI:10.3389/fimmu.2022.977175/full|DOI:10.1016/j.biocel.2016.02.003|DOI:10.3389/fimmu.2022.977175|DOI:10.3389/fendo.2018.00711 +101 CL:0000029 CL_0000029 "Neural crest derived neurons are specialized cells that arise from the neural crest during embryological development. The neural crest, a unique feature of vertebrates, is a transient, multipotent, migratory cell population that gives rise to a broad spectrum of cell types, including various neuron categories in the peripheral nervous system, such as chromaffin cells and enteric neurons. Neural crest derived neurons have a crucial role in establishing the intricate neural networks that connect the central nervous system to the rest of the body. + +The primary function of neural crest derived neurons is signal transduction and neurotransmission within the nervous system, leading to a variety of sensory, motor, and autonomic functions. To achieve this purpose, neurons such as the enteric neurons, which control the function of the gastrointestinal tract, have distinctive structural features including multi-branched dendrites to receive signals, and an elongated axon to send signals. + +In contrast, Chromaffin cells, another type of neural crest derived neurons, have lost their axon and dendrites. These cells are responsible for the systematic release of catecholamines such adrenalin and noradrenaline into the bloodstream and thereby play a critical role in the body’s response to stress induced by various external stimuli. + +Neural crest derived neurons are also involved in a variety of complex processes such as pain perception, thermoregulation, heart rate, and digestion, underscoring their versatility and functional diversity. Errors during the formation or function of these neurons can lead to a range of neurological conditions (‘Neurocristopathies’), such as Hirschsprung disease and familial dysautonomia. +" DOI:10.1146/annurev.cellbio.22.010305.103814|DOI:10.1038/nbt1365|DOI:10.1016/j.autneu.2009.07.020|DOI:10.1016/j.semcdb.2017.01.006|DOI:10.1126/science.1230717 +102 CL:0000099 CL_0000099 "Interneurons are a group of neurons that function as a link between sensory and motor neurons; most of them are found in the central nervous system, specifically in the brain and spinal cord, others are within the autonomic ganglia. These cells play a crucial role in the interpretation of sensory input, motor output, reflexes, and the overall communication between different neurons in the neural circuits. Interneurons make up about 99% of the neuron population in the body and are predominantly responsible for receiving signals from sensory neurons and transmitting these signals to motor neurons. + +Interneurons are characterized by their functionally diverse nature, with heterogeneity in their morphology, physiology, connectivity, and gene expression. Examples of interneurons include bipolar neurons, amacrine cells and horizontal cells in the retina, chandelier cells in the cortex, and ganglion interneurons, amongst many others. +The complex dendritic and axonal arborization patterns of interneurons allow for vast interconnections, ensuring a broad yet precise information processing. Generally, these cells contain inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA), which is involved in reducing neuronal excitability and counterbalancing the excitation induced by excitatory neurons. + +Furthermore, interneurons play an indispensable role in defining and refining the structural and functional organization of neural circuits. They are involved in several key neurophysiological mechanisms, including the regulation of critical period plasticity, modulation of neuronal synchronization, and control of network oscillation frequencies. Abnormalities in interneuron function have been correlated to several neurological disorders, such as epilepsy, schizophrenia, and autism, underscoring their critical functional role within the nervous system. + +In summary, interneurons carry out fundamental inhibitory functions within the neural circuitry, governing the fine balance between excitation and inhibition, and thereby ensuring normal brain function. +" DOI:doi.org/10.1038/nature12983|DOI:10.1038/nrn.2017.30|DOI:10.1016/j.tins.2003.12.008|DOI:10.1016/j.tins.2018.07.015|DOI:10.1038/nrn3155 +103 CL:0000091 CL_0000091 "Kupffer cells are tissue-resident macrophages located in the liver. They are an integral part of the mononuclear phagocyte system and are responsible for the phagocytosis of dead or dying cells, microbes, and other foreign substances. Kupffer cells account for approximately 80-90% of tissue-resident macrophages in the body. They are found within the lumen of liver sinusoids and interface with microbial populations and products. + +The primary role of Kupffer cells is to maintain homeostasis in the liver. They continuously filter and cleanse the blood that flows through the liver, removing pathogens, endotoxins, particulate matter, aged and dysfunctional red blood cells, and miscellaneous waste products. These cells also play an important role in maintaining iron homeostasis. During the process of phagocytosis, Kupffer cells recycle iron from degraded red blood cells, which is then utilized in the formation of new erythrocytes. + +Kupffer cells also play key roles in various immune responses and inflammatory processes. They secrete various types of cytokines and chemokines, which contribute to the activation and mobilization of other immune cells. They can also produce reactive oxygen species and nitric oxide, which have microbicidal actions. Although their activity is essential for host defense, excessive or prolonged activation of Kupffer cells may contribute to hepatic injury, inflammation, and fibrosis. +" DOI:10.1038/nri.2017.11|DOI:10.1016/j.immuni.2022.08.002|DOI:10.1002/cphy.c120026|DOI:10.1111/j.1478-3231.2006.01342.x|DOI:10.1007/978-1-4939-1311-4_10 +104 CL:0000095 CL_0000095 "Neuron associated cells include a variety of cells, in particular glial cells or neuroglia, the most abundant neuron associated cells, as well as vertebrate-specific cell types such as Merkel cells and oligodendrocytes. These cells play a vital role in maintaining the proper functioning of the nervous system and are intimately involved in all aspects of neuronal homeostasis and function. + +Glial cells are essential for providing both structural and nutritional support to neurons, regulating the neuronal microenvironment, and modulating signal transmission. Unlike neurons, neuroglia do not transmit nerve impulses but assist in the transmission process directly and indirectly by maintaining the necessary conditions for it. However, Merkel cells – another, much rarer type of neuron associated cells - have been shown to be touch-sensitive and transduce touch as part of the Merkel cell-neurite complex in the skin of most vertebrates. + +There are many different types of neuroglia, all performing specific functions in the nervous system. Astrocytes represent the most abundant neuron associated cells and play a critical role in maintaining the balance of interstitial fluid which surrounds the neurons; they do this by controlling the potassium ion concentration and reuptaking neurotransmitters. Oligodendrocytes and Schwann cells provide insulation to the neurons by forming the myelin sheath around the neuronal axons in the central and peripheral nervous system respectively, enhancing the speed and efficiency of electrical signal transduction. Microglia, which are the immune cells of the brain, play a protective role by releasing cytokines in response to pathogens and injuries to mediate inflammation and phagocytosing debris. + +While providing primarily support for neurons, neuron associated cells have crucial influence on neuronal function and the overall health of the nervous system. In pathological conditions, changes in the functions of these cells can contribute to neurodegenerative diseases such as Alzheimer's and Parkinson's. +" DOI:10.1016/j.biocel.2006.10.022|DOI:10.1016/j.biocel.2004.02.023|DOI:10.1002/ana.410440717|DOI:10.1038/nn1988 +105 CL:0000103 CL_0000103 "The bipolar neuron is a type of nerve cell primarily found mainly in the sensory systems of the human body. These specialized cells possess two distinctive extensions or processes - one axon and one dendrite, emerging from the cell body on opposite ends, which gives them their bipolar appearance. These two extensions serve as conduits for electrical signals, with the dendrite primarily playing the role of receiving signals, and the axon transmitting them further. + +Functionally, bipolar neurons are crucial in facilitating the transmission of special senses, particularly in the senses of sight, smell, hearing, and balance. For example, the bipolar neurons in the retina convey information about light intensity, color, and movement from the photoreceptors to the ganglion cells, forming part of the pathway for visual input to travel towards the brain. + +Similarly, in the olfactory system, the olfactory cells are bipolar neurons characterized by a peripheral process, called the olfactory rod, which projects fine cilia. These cilia are the sites of olfactory receptors which play a critical role in recognizing thousands of odorant molecules and transmit information about smell from the nose to the brain. + +Bipolar neurons are also involved in hearing. The vestibular ganglion contains thousands of bipolar neurons that receive sensory signals from hair cells in the inner ear. The nerve signals pass through the bipolar neurons and leave along the vestibular nerve. + +The morphology of bipolar neurons with their single dendrite and axon also subtly boosts their efficiency, maintaining a streamlined path for signal conduction. Their distinctive structuring allows for faster and more targeted relay of sensory information from the body's peripheries to the central nervous system. Loss or damage of these neurons would directly impact sensory reception and could lead to disorders related to vision, hearing, smell, or balance, underlining the significance of this cell type in the body's sensory capacity. +" DOI:10.1016/j.cell.2016.07.054|DOI:10.1038/nrn3783|DOI:10.1152/physrev.1986.66.3.772|DOI:10.1016/j.yexcr.2006.10.010|https://www.sciencedirect.com/topics/neuroscience/bipolar-neuron +106 CL:0000113 CL_0000113 "Mononuclear phagocytes are immune cells that form a critical part of the body's innate immune system, the body's first line of defense against infections. Mononuclear phagocytes are characterized by the presence of a single, large nucleus. The ‘Mononuclear Phagocyte System’ nomenclature was introduced to distinguish mononuclear monocytes and macrophages from other cells with multiple nuclei. However, the cells within the mononuclear phagocyte system represent a highly heterogeneous group, all of which are able to perform highly efficient phagocytosis - engulfing and digesting microbes and cellular debris to fight infections and to maintain normal tissue homeostasis. + +In addition to phagocytosis, mononuclear phagocytes also secrete chemical compounds to recruit other immune cells to a site of infection. These cells produce different types of signaling molecules, including cytokines, chemokines, and reactive oxygen species, triggering a cascade of responses to ensure rapid and efficient containment and neutralization of invading pathogens. These cells are also involved in antigen presentation, a process essential for stimulating an adaptive immune response. They can process and present antigens to T cells, thereby linking the innate and adaptive immune responses. + +Mononuclear phagocytes play key roles in tissue repair and remodeling. After infection or injury, these cells help in the clearance of dead cells and debris, a crucial step in the initiation of tissue remodeling and the resolution of inflammation. Overall, mononuclear phagocytes are versatile cells that have tailored their functions to meet the unique challenges of different tissues within the body. They are pivotal in homeostasis, immunity, and inflammation, making them important aspects in a range of human diseases including infection, autoimmunity, and cancer. +" DOI:10.1038/nri3087|DOI:10.1016/j.coi.2005.11.008|DOI:10.3389/fimmu.2019.01893|DOI:10.3389/fimmu.2019.01893 +107 CL:0000125 CL_0000125 "Glial cells, also known as neuroglia or simply glia, are non-neuronal cells in the central and peripheral nervous systems that provide support and protection for neurons. They constitute approximately half of the total cells in the human brain and more than half in other parts of the nervous system. Glial cells perform several key functions including, but not limited to, maintaining homeostasis, forming the myelin sheath around the neuron axons, and providing support and nutrition to neurons. + +These different functions are performed by various glial cell types, including astrocytes, oligodendrocytes, microglia and other specialized types. Astrocytes, for example, are the most abundant glial cells and provide metabolic and nutrient support to neurons, help regulate the extracellular ion and neurotransmitter levels, and play a role in the formation and maintenance of the blood-brain barrier, contributing to the overall homeostasis and functioning of the nervous system. Additionally, astrocytes are involved in synaptic communication and participate in processes such as synaptogenesis and synaptic pruning. + +Oligodendrocytes in the central nervous system function to insulate neurons by producing a fatty substance known as myelin. The myelin sheath enhances the speed and efficiency of nerve impulse conduction along the axons. + +Microglia, the immune cells of the central nervous system, protect neurons from pathogens and clear away dead neurons through phagocytosis, a process also known as cellular eating. They also contribute to the regulation of inflammation in response to signals of tissue damage or infection in the central nervous system by releasing cytokines and other signaling molecules that modulate the immune response. + +Despite their overarching function in the support and protection of neurons, glial cells have also been shown to play significant roles in the pathophysiology of many psychiatric and neurodegenerative diseases, such as Alzheimer’s, Parkinson’s Disease and multiple sclerosis. +" DOI:10.1126/science.aat0473|DOI:10.1101/cshperspect.a020602|DOI:10.1002/glia.24343|DOI:10.3389/fncel.2017.00024|DOI:10.1038/nn1988 +108 CL:0000121 CL_0000121 "Purkinje cells, named after the Czech anatomist Jan Evangelista Purkyně who discovered them, are unique inhibitory neurons in the cerebellar cortex. They are a critical part of the vertebrate nervous system as they provide the only signal output from the cortex to the cerebellar nuclei. They are one of the few types of neurons that are large enough to be seen with the naked eye. The most distinct hallmark of Purkinje cells is their elaborate dendritic arbor, which forms a broad and intricately branching structure resembling a tree. These numerous branches each receive excitatory synaptic inputs from more than 100,000 parallel fibers; in addition, a single climbing fiber makes hundreds of synapses to the soma and proximal dendrites. A single long axon forms an inhibitory projection to the cerebellar nuclei. + +Purkinje cells play key roles in the coordination of fine, voluntary motor movements and balance. As the sole output of all motor coordination in the cerebellar cortex, they serve as a central relay in the cerebro-cerebellar loop. Each Purkinje cell receives two types of synaptic input: one from parallel fibers (which are axons of granule cells), and the other from climbing fibers (originating from the inferior olivary nucleus). The Purkinje cells process and integrate these diverse kinds of input signals to generate output that controls timing and coordination of movements. + +Purkinje neurons show considerable synaptic plasticity. Throughout life, these cells continue to undergo long-term potentiation and depression at parallel fiber synapses, which cause long-lasting increase or decrease, respectively, of synaptic transmission and have been proposed as mechanisms for motor learning. + +Purkinje cells are also known to be implicated in a variety of diseases. Their progressive loss is a prime feature in certain types of ataxia, a collective term used to describe conditions characterized by loss of muscular control and coordination. Furthermore, a significant reduction in the density of Purkinje cells has been reported in conditions such as autism and Huntington’s disease. +" DOI:10.1007/s12311-018-0985-7|https://www.ncbi.nlm.nih.gov/books/NBK545154/|DOI:10.1038/nrn3886|https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/purkinje-cell|DOI:10.7554/eLife.63668 +109 CL:0000117 CL_0000117 "CNS neuron (sensu Vertebrata) represent the different types of neurons present in the Central Nervous System (CNS) specifically of vertebrates including mammals, birds, reptiles, amphibians and fish. CNS neurons form the basis of the complex network that drives the communication and information processing within the central nervous system comprised of the brain and spinal cord. Examples of neurons found in vertebrate central nervous systems include granule cells, Purkinje cells, stellate neurons, neuronal brush cells and many others. + +Fundamentally, CNS neurons play the key roles in receiving, processing, and transmitting neural information. They have specialized structures, such as the soma or cell body, dendrites that receive signals from other neurons, and an axon that transmits information to other cells through synapses. Different types of CNS neurons have adapted structurally to their specific functions within the CNS. For example, Purkinje cells, which are a unique type of neuron that provide the sole output of the cerebellar cortex, are characterized by massive, intricately branched, flat dendritic trees, which allow them integrate large amounts of neural signals. +Importantly, CNS neurons have the distinctive capability of generating electrical signals known as action potentials, which is a fundamental process in neuronal communication. This communication process, which occurs across complex neuronal networks, is responsible for all cognitive functions - ranging from basic reflexes to advanced functions like memory formation and critical thinking. + +CNS neurons can be further classified into subtypes based on their functions, such as sensory neurons, motor neurons and interneurons. Sensory neurons transmit sensory information from peripheral body parts to the central nervous system, hence playing a crucial role in perception of the environment and body condition. Motor neurons, on the other hand, carry signals from the central nervous system to peripheral body parts (like muscles), enabling actions and movements. Interneurons in the CNS act as the mediators and communicators between sensory and motor neurons, hence playing a vital role in the coordination of sensory inputs and motor outputs. +" DOI:10.1096/fasebj.8.10.8050671|DOI:10.1016/j.gde.2020.05.043|DOI:10.1016/S0166-2236(96)10075-8|DOI:10.1038/nrn2151|DOI:10.1016/j.stem.2016.10.015 +110 CL:0000126 CL_0000126 "Macroglial cells are a type of glial cell found within the nervous systems of vertebrates. They are integral to maintaining the overall health and functionality of the nervous system. Astrocytes and oligodendrocytes are the two most numerous and functionally important types of macroglia, playing different yet crucial roles in the functioning of the nervous system. + +Astrocytes are functionally and morphologically diverse and are distributed throughout the brain and spinal cord. They are involved in nutrient transport from the blood to the brain, formation of the blood-brain barrier, secretion of growth factors, and synaptic transmission regulation. A key feature of astrocytes is the expression of glial fibrillary acidic protein (GFAP). Many astrocytes fall into two major classes - fibrous astrocytes are present in white matter and support axons, protoplasmic astrocytes are found in gray matter and have a primary role in supporting the blood-brain barrier. Other specialized astroglial cells include ependymoglial cells which line the cavities of the brain and spinal cord where cerebrospinal fluid (CSF) is produced and circulated. + +Oligodendrocytes, another type of macroglial cells, are cells that produce myelin, a fatty substance that covers axons, increasing the speed and efficiency of the electrical signals transmitted by neurons. Myelin is crucial for ensuring proper electrical insulation of these nerves, and thus, the proper function of the nervous system. + +Dysfunction in macroglia has been associated with various diseases and conditions, including Glioblastoma multiforme, an aggressive type of astrocytoma, and Alexander Disease, a rare neurological disorder which is characterized by the abnormal accumulation of GFAP in astrocytes. Recent studies also suggest that dysfunction of astrocytes can contribute to the pathology of Alzheimer's Disease and Amyotrophic Lateral Sclerosis. +" DOI:10.1007/s00441-017-2746-1|DOI:10.1038/nature09611|DOI:10.1007/s00401-009-0619-8|DOI:10.1007/s00401-009-0601-5|DOI:10.1038/s41467-019-14198-8 +111 CL:0000164 CL_0000164 "Enteroendocrine cells are a specialized subset of cells located within the epithelial lining of both the small and large intestines, as well as the stomach and pancreas. Constituting less than 1% of the total population of intestinal cells, they are differentiated from a common intestinal cell progenitor, thus sharing lineage with absorptive and goblet cells of the intestines. + +The distinct characteristic feature of an enteroendocrine cell is its inherent capacity to synthesize and secrete a plethora of gut hormones such as serotonin, somatostatin, neurotensin, cholecystokinin, secretin, gastric inhibitory peptide, motilin, and glucagon-like peptide-1. Integrated within this complex network of signaling agents, these substances control various aspects of the digestive system. Each enteroendocrine cell has its unique combination of hormones to release, determined by its position along the intestinal tract. Intriguingly, these hormones not only modulate local gut function, including motility, absorption and secretion, but also potentiate distant actions on other systems such as endocrine, nervous and immune and play a role in the feeling of satiety. + +The release of these hormones from enteroendocrine cells is a highly regulated and dynamic process. The cells are equipped with sensory receptors localized on its luminal side that respond to various stimuli, including changes in nutrient composition, chemical or mechanical changes in the gut lumen, or even signals arising from commensal microbiota. This sensory input stimulates a signaling cascade within the cell, culminating in the release of specific hormones into the interstitial fluid. These hormones then make their way into the bloodstream, acting on their respective target receptors to mediate their duties. The multifunctional characteristics of enteroendocrine cells make them crucial for maintaining gut homeostasis and the overall physiological well being of the body. +" DOI:10.1038/s41574-019-0168-8|DOI:10.1210/endrev/bnaa018|DOI:10.1111/j.1463-1326.2011.01438.x|DOI:10.7554/elife.78512|DOI:10.1196/annals.1294.001 +112 CL:0000160 CL_0000160 "Goblet cells are specialized, simple columnar, secretory epithelial cells that are mostly found in the respiratory and intestinal tracts. The term ""goblet"" refers to their shape, which resembles a flask or goblet, specially at their apical end which is swollen due to the accumulation of secretory granules. + +The primary function of goblet cells is to to protect and lubricate the underlying tissues by secreting large quantities of mucin, a complex glycoprotein, which forms mucus when hydrated. In the respiratory tract, the mucus secreted by these cells traps dust, bacteria, viruses, and other potentially harmful particles in the inhaled air, preventing them from reaching the delicate tissues of the lungs. In the intestines, the goblet cells secrete mucus that acts as a protective barrier shielding the intestinal epithelium from dietary antigens, pathogens and prevents the intestinal epithelium from being eroded by the actions of the digestive enzymes and the abrasive action of passing food material. + +Goblet cells are capable of rapidly altering their secretory output in response to stimuli. For example, irritants like smoke or dust can trigger an increased rate of mucus production, as the body attempts to flush out the harmful particles. Conversely, in conditions such as chronic bronchitis and cystic fibrosis, overactive goblet cells can create a thick accumulation of mucus that obstructs the airways and fosters bacterial growth. Lastly, goblet cells are not static, rather, they undergo a dynamic process known as goblet cell metaplasia-differentiation, wherein non-goblet cells in response to chronic injury or inflammation, can differentiate into goblet cells leading to an accumulation of these cells in the tissue, known as goblet cell hyperplasia." DOI:10.1038/s41575-022-00675-x|DOI:10.1016/S1357-2725(02)00083-3|DOI:10.1165/ajrcmb.25.5.f218|DOI:10.1242/bio.20121701|https://www.ncbi.nlm.nih.gov/books/NBK553208/ +113 CL:0000182 CL_0000182 "Hepatocytes are the major cell type constituting 70-80% of the liver's cytoplasmic mass, playing crucial roles in maintaining the body's metabolic homeostasis. Dimensions of mature hepatocytes typically range from 20 to 30 μm in humans, but size may vary depending on their location within the liver lobule. Hepatocytes are characterized by high biosynthetic, enzymatic, and endocytic activity. They contain abundant mitochondria, smooth and rough endoplasmic reticulum, peroxisomes, lysosomes, and a large nucleus that is often binucleate. + +The liver consists of three zones - the periportal Zone 1, midzone 2, and pericentral Zone 3 - which have differential nutrient and oxygen status, and damage susceptibility; hepatocytes in the different zones show signifcant functional heterogeneity ('hepatocyte functional zonation'). Hepatocytes are involved in a multitude of critical functions including the metabolism of lipids, carbohydrates, and proteins, the synthesis of serum proteins (e.g., albumin, transferrin, and lipoproteins), the detoxification and excretion of endogenous and exogenous substances, the storage of vitamins and minerals, and the production and secretion of bile. + +Heterocytes demonstrate a remarkable regenerative capacity, which enables the liver to recover from injury and loss of tissue mass. Notably, hepatocytes perform biotransformation with both phase I and phase II enzymes, which modify drugs, xenobiotics, and various substances for elimination from the body. Phase I enzymes, such as cytochrome P450, catalyze both oxidative and reductive reactions of many xenobiotics; many of the products of phase I enzymes are substrates for the phase II enzymes, which catalyze conjugation reactions. + +Alterations in hepatocyte function have significant implications for overall human health and disease. Certain conditions, such as hepatitis, cirrhosis, and liver cancer, can profoundly affect hepatocyte structure and function, thereby disrupting the liver's ability to perform its vital roles within the body. As the primary site for drug metabolism, changes in hepatocyte function can also impact the effectiveness and toxicity of pharmaceuticals. The regenerative ability of hepatocytes makes them valuable cells for liver regenerative medicine and bioartificial liver support systems, and their study has provided significant insights into liver biology and disease." DOI:10.1083/jcb.201903090|DOI:10.1111/j.1439-0396.2007.00752.x|DOI:10.1016/j.biocel.2011.11.011|DOI:10.1016/j.biocel.2011.11.011|DOI:10.1055/s-2007-1007096 +114 CL:0000178 CL_0000178 "Leydig cells are a testosterone-secreting cell in the interstitial area in the testes of males. They are named after Franz Leydig, a German anatomist who discovered these cells in 1850. Uniquely situated within the soft connective tissue surrounding the seminiferous tubules, Leydig cells form an integral part of the male reproductive system. They are usually polygonal cells characterized by well developed smooth endoplasmic reticulum, high lipid content and a large round nucleus. They are found across mammalian species, including humans. + +The primary function of Leydig cells is the production of androgens, the male sex hormones, the most notable of which is testosterone. Leydig cells synthesize testosterone from cholesterol through a series of enzymatic reactions. The production and release of testosterone are mainly regulated by the luteinizing hormone (LH) released by the anterior pituitary gland. In response to LH, Leydig cells convert cholesterol into testosterone, which then plays a crucial role in the development and maintenance of primary and secondary male sexual characteristics. These include the formation and maturation of male reproductive organs, onset of spermatogenesis, and the presentation of male secondary sexual traits such as the deepening of the voice, growth of facial hair, development of muscles, and a broadening of shoulders. + +Apart from testosterone production, Leydig cells also secrete insulin-like factor 3 (INSL3) that is essential for testicular descent during embryonic development in males. Dysregulation or loss of Leydig cells can lead to numerous conditions like testosterone deficiency, infertility, and certain forms of testicular cancer. Although not typical, Leydig cells can regenerate if they are damaged, ensuring the continuous production of testosterone and maintaining male reproductive health. They provide an excellent model to study cell differentiation and hormone regulation, thereby enhancing our understanding of reproductive biology and associated disorders. + + +" DOI:10.1093/biolre/ioy059|DOI:10.3389/fendo.2014.00006|DOI:10.1210/clinem/dgaa603|https://www.ncbi.nlm.nih.gov/books/NBK556007/#:~:text=Leydig%20cells%20are%20the%20primary,secondary%20sexual%20characteristics%20and%20behaviors.|DOI:10.1016/j.coemr.2019.03.001 +115 CL:0000235 CL_0000235 "Macrophages are specialized white blood cells involved in immune responses, inflammation, and tissue repair. Tissue-resident macrophages can be self-renewing and arise from embryo-derived populations. Macrophages can also originate from circulating monocytes that differentiate into macrophages upon migration into body tissues. + +Macrophages are involved in the detection, phagocytosis, and destruction of bacteria and other pathogens. They are also responsible for engulfing and removing dead cells and debris. Macrophages are also one of the cells that present pathogenic antigens to T cells so that the pathogens may be recognized and killed, or so that an antibody response may be mounted. They can also secrete cytokines, chemokines, and enzymes that further orchestrate the immune response. + +Tissue-resident macrophages are diverse and heterogenous, likely as a result of the signals received from the tissue environment. The functions of these macrophages are specific to each tissue and contribute to tissue homeostasis. Dysregulation of macrophage functioning may also contribute to the development of various disease processes, such as fibrosis, chronic inflammation, or cancer. +" DOI:10.1016/j.immuni.2016.02.015|DOI:10.1146/annurev-immunol-032414-112220|DOI:10.1038/ni.2705|DOI:10.1093/intimm/dxy054|DOI:10.3389/fimmu.2021.708186 +116 CL:0000234 CL_0000234 "Phagocytes are a heterogeneous group of white blood cells that have the capability to ingest, or ‘phagocytose’, foreign substances, pathogens, and cellular debris with high efficiency, thereby playing a vital role in the immune response. Phagocytes circulate throughout the body, patrolling and guarding against the invasion of pathogens. They are one among many types of cells that originate from hematopoietic stem cells in the bone marrow. + +Upon detection of an invading microorganism, phagocytes are mobilized by inflammatory mediators (such as bacterial proteins or complement proteins) to the infection site. They recognize surface molecules, specifically antigens, on harmful bacteria or other foreign substances with the help of opsonins, which are proteins that bind to the pathogen and make them more susceptible to phagocytosis. The process of phagocytosis involves the extension of the phagocyte's membrane around the microorganism, completely enclosing it within a microbicidal vacuole, the phagolysosome, which contains various microbicidal chemicals and digestive enzymes such as cathepsins, proteases, lysozymes, and lipases that may be employed to degrade the pathogen. + +Phagocytes are predominantly neutrophils or monocytes. Neutrophils are the most abundant type of phagocyte and are usually the first to arrive at the site of infection. Monocytes are derived from the bone marrow and can circulate to tissues and mature into local macrophages. Macrophages arrive later at sites of infection and are longer-lived than neutrophils. The process of phagocytosis must be tightly regulated to avoid host tissue damage. +" DOI:10.1016/B978-0-12-809633-8.90746-5|DOI:10.1016/B978-0-08-046884-6.00607-2|DOI:10.1182/blood-2007-12-077917|DOI:0.3389/fimmu.2020.01066|DOI:10.1086/374747 +117 CL:0000501 CL_0000501 "Granulosa cells are a type of somatic cell most commonly known for their crucial role within the ovarian follicles of female mammalian species. Named for their grainy appearance, they are situated in the follicular epithelium, lining the inner part of the follicle and directly surrounding the oocyte. These cells stand as an integral part of the ovarian structure and function. + +One of the primary roles of granulosa cells is to aid in the production and secretion of sex hormones, particularly estrogen. They achieve this by working in tandem with theca cells, which stay attached to the external layer of the follicle. Theca cells produce androstenedione (a type of androgen) which granulosa cells then convert into estradiol, a form of estrogen, with the help of the enzyme aromatase. Moreover, granulosa cells participate in luteinization, transforming into luteal granulosa cells as a response to the luteinizing hormone during ovulation. This allows the formation of the corpus luteum, responsible for the secretion of progesterone necessary to maintain pregnancy. + +Granulosa cells also play a significant role in follicular development and oocyte maturation, involving close communication with the contained oocyte. They support the oocyte through the provision of nutrients and growth factors, control its meiotic cycle and ensure it is appropriately oriented and instructed for impending ovulation. Furthermore, granulosa cells contribute to the formation of the zona pellucida and the follicular fluid, providing an optimal environment for the oocyte's growth and maturation. These cells, thus, perform multiple vital roles, underscoring their importance in fertility and reproductive health. +" DOI:10.1016/j.ejogrb.2004.01.010|DOI:10.1093/humrep/del408|DOI:10.1210/jcem-28-3-355|DOI:10.3389/fendo.2019.00832/full|DOI:10.1093/humupd/6.3.279 +118 CL:0000502 CL_0000502 "Type D enteroendocrine cells, also known as D or delta cells, are specialized hormone-releasing cells found in the pancreas and also scattered throughout the lining of the gastrointestinal tract in mammals, notably within the stomach and the upper part of the small intestine known as the duodenum. The primary role of D cells is to produce and secrete somatostatin, a potent paracrine inhibitor. + +In the gastrointestinal tract, somatostatin slows down digestion. It reduces gastric acid secretion and slows down the rate of gastric emptying, thereby prolonging and controling the digestive p. Functionally, these effects are aimed at sustaining nutrient absorption to optimize energy extraction from consumed food. + +In the pancreas, D cells maintain a vital role in endocrine regulation. D cells in the pancreatic islands secrete somatostatin to inhibit the release of both insulin and glucagon from type A cells and B cells, glucoregulatory hormones that control blood sugar levels. Hence, D cells contribute considerably to the homeostasis of the body's metabolic processes. It is also noteworthy that dysfunctional D cells or irregular somatostatin signaling has been associated with certain pathologies such as neuroendocrine tumors and gastric ulcers. +" DOI:10.1038/s41574-018-0020-6|DOI:10.1016/j.pharmthera.2015.05.007|DOI:10.1093/annonc/mdh216|https://www.sciencedirect.com/topics/neuroscience/somatostatin-cell +119 CL:0000510 CL_0000510 "Paneth cells are specialized epithelial cells that are primarily located at the bottom of the crypts of Lieberkühn in the small intestine, where they play a pivotal role in maintaining gut homeostasis. They have also been found in smaller numbers in the colonic crypts and other parts of the gastrointestinal tract. Paneth cells are characterized by large acidophilic granules, which take up most of the cytoplasmic volume, causing the nucleus to be pushed toward the base of the cell. + +Paneth cells function as a part of the innate immune system. The large granules inside the cells are filled with antimicrobial peptides, such as defensins and lysozymes. Upon bacterial intrusion or cellular signaling indicating a potential infection, Paneth cells release the granules containing the antimicrobial substances into the crypt lumen, effectively serving as the first line of defense against bacterial invasion within the gastrointestinal tract. In essence, Paneth cells serve as guardians, protecting the intestinal stem cells from harmful pathogens that may disturb the gut ecosystem. + +In addition to their primary role in immunity, Paneth cells are also crucial for supporting the stem cell niche in the intestinal crypts. They are located adjacent to Lgr5+ stem cells and secrete various growth factors such as EGF, TGF-alpha, Wnt3, and Notch ligand Dll4. These factors regulate the self-renewal and differentiation of these stem cells, which continuously replenish the intestinal epithelium. Consequently, any abnormality or dysfunction in Paneth cells could lead to a disturbance in gut homeostasis, possibly resulting in various illnesses such as inflammatory bowel disease. +" DOI:10.1146/annurev-physiol-030212-183744|DOI:10.1038/nrmicro2546|DOI:10.1038/nature09637|DOI:10.1007/s00018-002-8412-z|DOI:10.3389/fimmu.2020.00587 +120 CL:0000577 CL_0000577 "Type EC enteroendocrine cells, also known as enterochromaffin cells, are a vital hormone-secreting cell type found in the gastrointestinal tract. These cells are named after their location in the intestines (“entero”) and because they are stainable by chromium salts (“chromaffin”). + +The primary function of type EC enteroendocrine cells is to act as chemosensors and lies in their capacity to produce and secrete serotonin, also known as 5-hydroxytryptamine (5-HT). Serotonin is a neurotransmitter that plays a significant role in modulating motility, secretion, vasodilation, perception of pain, and appetite in the gastrointestinal system. However, its function is not limited to the gastrointestinal tract; once secreted, serotonin is distributed via the bloodstream and contributes to regulating mood, appetite, and sleep in the brain. + +Via specific chemosensory receptors type EC enteroendocrine cells are able to respond to various environmental, metabolic, and homeostatic stimuli and transduce information from the gut to the nervous system: Food intake, particularly the ingestion of fats and carbohydrates, prompts these cells to produce and release serotonin; the mechanical stimulus of food in the lumen can also trigger release. The distribution, function, and responsiveness of type EC cells reveal them as a crucial link between the intestinal environment, the nervous system, and the regulation of numerous bodily functions. +" DOI:10.1016/j.cell.2017.05.034|DOI:10.1016/0166-4328(96)00075-7|DOI:10.1038/s41574-019-0168-8|DOI:10.1073/pnas.1804938115 +121 CL:0000583 CL_0000583 "Alveolar macrophages are unique tissue-resident macrophages found in the lungs, specifically in the air sacs or alveoli where gas exchange occurs. They are characterized by specific surface markers including: F4/80-positive, CD11b-/low, CD11c-positive, CD68-positive, sialoadhesin-positive, dectin-1-positive, MR-positive, CX3CR1-negative. These specialized immune cells form a crucial part of the body's defense mechanism, playing important roles in pulmonary health and homeostasis. They are the first line of defense in the pulmonary immune response, acting as scavengers that patrol the alveoli and engulf foreign particles like bacteria, dust, and other debris that enter the lungs through inhalation. + +The primary function of these alveolar macrophages is phagocytosis, whereby they consume and digest foreign substances, dead cells, and other particulates. In the lung, alveolar macrophages are also responsible for clearing surfactant. Additionally, alveolar macrophages also play an integral role in initiating the immune response, as they secrete several pro-inflammatory cytokines and chemokines that recruit other immune cells to the site of infection or inflammation. + +Beyond their role in host defense, alveolar macrophages contribute to tissue remodeling and wound repair in the lungs, aiding in maintaining lung integrity. They also regulate local inflammation and control the immune response to prevent excessive inflammation that may be harmful. However, an imbalance in the function of alveolar macrophages can contribute to various lung diseases. Abnormal alveolar macrophage activation has been implicated in chronic inflammatory diseases such as emphysema, asthma, and fibrosis. +" DOI:10.1016/j.cellimm.2018.01.005|DOI:10.1038/nri3600|DOI:10.14348/molcells.2021.0058|DOI:10.1007/s00424-017-1965-3 +122 CL:0000622 CL_0000622 "Acinar cells are specialized exocrine gland cells that secrete specific enzymes and fluids to aid in digestion. Found primarily in the pancreas and salivary glands, the term acinar is derived from the Latin word 'acinus' which means 'grape'; this is because acinar cells are arranged in a grape-like cluster around small ducts, formulating an acinus structure. + +In the salivary glands, acinar cells secrete digestive enzymes as well as other substances such as mucus and water. These secretions service the initial stages of the digestive process, preparing the consumed food for onward digestion in the stomach and intestines by lubricating and partially breaking it down. + +In the pancreas, acinar cells are responsible for synthesizing and secreting a significant amount of digestive enzymes, such as trypsin, chymotrypsin, and amylase. These enzymes are stored in zymogen granules inside the acinar cells until they are dispatched into the small intestine. Once within the small intestine, they break down proteins, carbohydrates, and fats into substances that can be absorbed. This is vital to the effective and efficient digestion and absorption of nutrients from the food we consume. + +Acinar cells have high protein synthesis rates and are susceptible to accumulation of misfolded proteins; the subsequential induction of ER stress is thought to be involved in the development of pancreatitis, a serious inflammatory disease of the exocrine pancreas. +" DOI:10.1097/MOG.0b013e32832ebfac|DOI:10.1038/nrgastro.2013.36|DOI:10.1007/BF00710764|DOI:10.1111/prd.12116|DOI:10.1152/physrev.00011.2011 +123 CL:0000653 CL_0000653 "Podocytes are highly specialized, terminally differentiated glomerular visceral epithelial cells that wrap around the capillaries in the kidneys. They play an essential role in kidney function, particularly in the filtration selectivity of the glomerulus. Each podocyte is characterized by a unique architecture with a large cell body, ‘major processes’ extending outwardly from the cell body and ‘foot processes’, also known as pedicels, which surround. the glomerular capillary loops + +Podocytes represent the last barrier of the glomerular filtration membrane in the kidney. This barrier prevents the leakage of plasma proteins from the blood into the urine, hence maintaining protein homeostasis in the body. The foot processes of the podocytes interdigitate with those from neighboring cells. The cell-cell junctions between the foot processes, the slit-diaphragms, are thought to create a molecular sensor of renal filtration that prevents the passage of macromolecules while allowing water and small solutes to pass. +Podocytes also contribute to the glomerular basement membrane by secreting collagen and maintain glomerular endothelial cell fenestration by secreting VEGFA. They have been shown to play a role in inducing cytoskeletal regulation, cell adhesion, and inflammatory response, consistent with their essential function in the kidney. + +The importance of podocytes is further emphasized by the effects of their damage or loss. Abnormalities in podocytes often result in severe kidney diseases (podocytopathies), including focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). Injury to the podocytes can result in ""effacement"" or flattening of foot processes, leading to increased permeability of the filtration barrier and proteinuria (an excess of serum protein in urine) which is a common symptom of kidney diseases. +" DOI:10.1159/000481633|DOI:10.1038/s41572-020-0196-7|DOI:10.3389/fcell.2021.771931|DOI:10.1038/s41467-022-33748-1|DOI:10.1146/annurev-physiol-020911-153238 +124 CL:0000666 CL_0000666 "Fenestrated cells are specialized epithelial cells that are characterized by a distinctive structural feature, fenestrations or tiny pores, which allow an exchange of substances such as fluids, nutrients, and waste between blood vessels and the surrounding tissue environments. These cells are present in various types of epithelial tissues in the human body, including the intestinal tract, endocrine glands, and certain parts of the renal system. + +There are multiple types of endothelial cell fenestrations. The most common type is found in systemic capillaries of the endocrine tissue (e.g., pancreatic islets), gastrointestinal mucosa, and renal peritubular capillaries. Here, the fenestrated cells have fenestrations in their peripheral cytoplasm with a unique thin and permeable diaphragm that provides a high degree of selectivity, blocking the passage of larger molecules while allowing the free movement of smaller ones. In contrast, other types of fenestrations, such as the discontinuous epithelium of the liver sinusoidal endothelial cells, do not have diaphragms. + +Characteristically, fenestrated cells play a vital role in the filtering process of body systems. They are a key part of the glomeruli in the kidneys where blood is filtered under high pressure. The fenestrations present in the endothelial cells lining the capillaries of the glomerulus allow the free passage of water and small solute molecules towards the Bowman's capsule, leaving behind larger proteins and cells in the blood, thereby aiding in the filtration and waste removal process. + +In the endocrine system, fenestrated cells in glandular capillaries allow the prompt release of hormones into the bloodstream. These cells have tightly clustered fenestrations which increase the surface area available for passive diffusion, improving the efficiency of hormone secretion. In villi of the small intestine, these cells increase absorption efficiency, permitting the exchange of water, electrolytes, and nutrients. + +Overall, fenestrated cells contribute immensely to important physiological processes of filtration, absorption, and secretion, primarily connecting our body's circulation system with the surrounding tissues and organs. +" DOI:10.1016/j.devcel.2012.11.003|DOI:10.1152/ajprenal.90601.2008|DOI:10.1016/0306-4522(86)90162-4|DOI:10.1002/ar.1092200109|DOI:10.1038/s41467-022-31571-2 +125 CL:0000682 CL_0000682 "M cells, or microfold cells, of the gut are specialized epithelial cells found in the lining of the gut, specifically in the follicle-associated epithelium of mucosa-associated lymphoid tissue, where they function as sentries against toxins and pathogens. M cells are characterized by apical microfolds (hence their alternate name) which express unique adhesion molecules that enable them to sample the luminal macromolecules. + +Other morphological features that distinguish M cells from other intestinal mucosal cells include sparse microvilli and a reduced thickness of the glycocalyx, which permits adhesion while not hindering the transport of molecules. They also have unique intraepithelial invaginations on the basolateral side which are filled with macrophages and other immune cells that can process the engulfed macromolecules quickly. + +These morphological characteristics enable M cells to serve a dual role in immune responses. They initiate the immune response by transporting antigens (such as toxic or pathogenic substances) across the epithelial layer to lymphocytes and antigen-presenting cells in the underlying lymphoid tissue. This specialized transport process is called 'transcytosis.' They also have specialized molecules like glycoprotein-2 for bacterial uptake. Simultaneously, M cells help maintain immune tolerance to food antigens and commensal bacteria, preventing unnecessary reactions to non-pathogenic substances and hypersensitivity conditions. While these functions are crucial for well-being, M cell dysfunction can lead to serious conditions like Crohn's disease and other inflammatory bowel diseases. + +" DOI:10.1093/jb/mvv121|DOI:10.1136/gut.47.5.735|DOI:10.1038/nature08529|https://www.ncbi.nlm.nih.gov/books/NBK534232/|https://www.sciencedirect.com/topics/medicine-and-dentistry/microfold-cell +126 CL:0000696 CL_0000696 "PP cells, also known as pancreatic polypeptide cells (and previously called F cells or gamma cells), are enteroendocrine cells predominantly found in the islets of Langerhans in the head of the pancreas. They are one of the four main endocrine cell types present in the pancreatic islets, along with type A, B and D cells. PP cells are notable for their production of pancreatic polypeptide, an anorexigenic hormone that modulates food intake and energy homeostasis. + +By secreting pancreatic polypeptide, PP cells play a significant role in the management of both digestive and appetite regulation. Upon ingestion of food, there is a significant increase in the secretion of pancreatic polypeptide, which then reduces biliary secretion and helps slow down the movement of food through the digestive tract. This allows more time for digestion to take place and nutrients to be absorbed, promoting the efficient use of dietary intake. The pancreatic polypeptide further reduces appetite by interacting with the hypothalamus, the area of the brain responsible for control of hunger. + +Given their important role in digestion, malfunction or damage to PP cells can lead to a disturbance in the digestive process and contribute to some disease conditions. For example, an overproduction of pancreatic polypeptide can result in conditions such as pancreatic tumors and diabetes. Conversely, an under secretion might contribute to obesity due to impaired dietary control. Furthermore, PP cells may also play a role in the body's energy balance, suggesting their implication in conditions related to energy metabolism. +" DOI:10.1369/00221554155835|DOI:10.1210/jc.2003-030630|DOI:10.1016/j.mce.2015.06.028|DOI:10.1016/j.febslet.2014.07.005|DOI:10.1038/s41580-020-00317-7 +127 CL:0000860 CL_0000860 "Classical monocytes are a subtype of monocytes that are characterized by high CD14 but no CD16 expression. Emerging from the bone marrow and entering the bloodstream, these cells play central roles in immune responses and regulation of inflammation. CD14-positive CD16-negative monocytes form the majority of circulating monocytes in the body, typically contributing to around 80-90% of the total monocyte pool. + +The primary function of the classical monocytes is to serve in the frontline of host defense against infections. They are primed to migrate to sites of infection, and they express pattern recognition receptors that help them identify and phagocytose pathogens, leading to their destruction. Classical monocytes also contribute to inflammation by producing several pro-inflammatory cytokines including interleukins and tumor necrosis factors. + +In response to specific signals from tissues under pathological conditions, such as infection or injury, classical monocytes can leave the bloodstream and migrate towards the affected sites. Following their arrival, these cells differentiate into diverse cell types including macrophages and dendritic cells to combat specific pathogens or injury. Dysregulated monocyte activity can lead to the development of many human diseases including inflammation, infection, tissue injury, and various autoimmune diseases. +" DOI:10.1111/sji.12883|DOI:10.3389/fimmu.2015.00423/full|DOI:10.1182/blood-2009-07-235028|DOI:10.3389/fimmu.2019.02035|DOI:10.1038/nri.2017.28 +128 CL:0000863 CL_0000863 "Inflammatory macrophages, also sometimes referred to as M1 or classically activated macrophages, play an important role in the inflammatory response. The M1/M2 classification is based upon macrophage polarization rather than macrophage location and refers to macrophage activation towards either a more inflammatory or more resolving phenotype, respectively, although the functional diversity of macrophages is more nuanced than such a dichotomy suggests. + +Inflammatory macrophages are derived from monocytes recruited to a site of infection or injury. M1 macrophages are classically activated, typically by IFN-γ or lipopolysaccharide (LPS). Upon sensing signs of inflammation, they quickly respond by increasing their pro-inflammatory activity. They achieve this by producing a range of signaling molecules, such as nitric oxide, reactive oxygen species, and numerous cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1, -6 and -12. The release of these potent molecules helps to recruit other immune cells to the site, killing off pathogenic organisms and facilitation inflammation. At the same time, M1 macrophages can also present antigens to T cells, thereby helping to induce an adaptive immune response. Over time, these macrophages may transition in phenotype and function to help resolve the inflammation and promote tissue repair. + +Despite the beneficial role of inflammatory macrophages in dealing with pathogens, chronic activation of these cells can lead to harmful effects. Over time, continuous production of pro-inflammatory molecules can cause damage to tissues and organs. This is seen in certain chronic inflammatory diseases, such as atherosclerosis, diabetes, obesity, asthma, and various autoimmune disorders. In such situations, the normally protective function of inflammatory macrophages is not properly controlled, which can contribute to disease pathology. +" DOI:10.1038/s41392-023-01452-1|DOI:10.1186/s12935-021-02089-2|DOI:10.3389/fimmu.2020.583084|DOI:10.3389/fimmu.2015.00263 +129 CL:0000864 CL_0000864 "Tissue-resident macrophages refer to a heterogeneous group of specialized macrophages that permanently reside within specific tissues, performing integral functions essential to tissue homeostasis. Most tissue-resident macrophages arise from embryonic populations and self-renew. Some macrophages may also originate from circulating monocytes released from the bone marrow and differentiate into macrophages upon entering tissue. Tissue-resident macrophages are given different names depending upon the tissue in which they reside, such as Kupffer cells in the liver, alveolar macrophages in the lungs, and microglia in the brain. + +Tissue-resident macrophages are responsible for the phagocytosis of pathogenic substances and dead cells, serving as part of the foremost line of defense against invading microorganisms. They utilize pattern recognition receptors to identify foreign substances and function as antigen-presenting cells to induce adaptive immunity. Additionally, they produce a variety of cytokines and chemokines, signaling molecules that recruit additional immune cells to sites of infection or inflammation and regulate immune responses. + +In addition to their immunological roles, tissue-resident macrophages also have tissue-unique functions. In the liver, Kupffer cells play a role in iron homeostasis, while in the brain, microglia are responsible for synaptic pruning during development. In the lungs, alveolar macrophages are involved in the removal of airborne particles and debris. This underscores their significance in not only providing pathological immunity but also in maintaining the optimal function of the tissues in which they reside. """ DOI:10.1016/j.immuni.2016.02.015|DOI:10.1146/annurev-immunol-032414-112220|DOI:10.1038/s41392-023-01452-1|DOI:10.1093/intimm/dxy054 +130 CL:0000890 CL_0000890 "Alternatively activated macrophages, also referred to as M2 macrophages, are immune cells originating from monocytes. The M1/M2 classification is based upon macrophage polarization rather than macrophage location and refers to macrophage activation towards either a more inflammatory or more resolving phenotype, respectively, although the functional diversity of macrophages is more nuanced than such a dichotomy suggests. + +M2 macrophages cells are differentiated from their precursors generally in response to Th2 cytokines, such as interleukin-4 (IL-4), interleukin-10 (IL-10), and interleukin-13 (IL-13). Tissue-resident macrophages are also sometimes said to have an “M2-like” phenotype. M2 macrophages play key roles in immunoregulation and disease resolution. + +Functionally, alternatively activated macrophages are essential in wound healing and tissue repair and remodeling, largely due to their potent anti-inflammatory actions and their ability to promote angiogenesis. They achieve these functions by the production of specific growth factors and signaling proteins including Arg1, Ym1/2, Fizz1, and TGF-β. Additionally, they provide defense against specific categories of pathogens, particularly parasites, through specific communication with Th2 cells. + +However, dysfunction of M2 macrophages can be harmful. Alternatively activated macrophages have been associated with several pathological conditions such as asthma, fibrosis, and tumor progression. This is due to their capacity to inhibit inflammatory responses, promote unneeded wound healing processes, and support tumour growth and spreading. Furthermore, complex roles have been observed in metabolic disorders, cardiovascular diseases, and neurodegenerative diseases, showing the diverse functional spectrum of these cells. +" DOI:10.1038/s41392-023-01452-1|DOI:10.1186/s12935-021-02089-2|DOI:10.3389/fimmu.2020.583084|DOI:10.3389/fimmu.2015.00263 +131 CL:0002064 CL_0002064 "Pancreatic acinar cells are the functional units of the exocrine pancreas. These cells are structurally arranged in small clusters - or acini - with a small central lumen, and their primary function is to produce and secrete enzymes that facilitate digestion of proteins, carbohydrates, and fats within the small intestine. + +Some of the most important digestive enzymes synthesized by the pancreatic acinar cells include amylase, which digests carbohydrates, lipase, which breaks down fats, and several proteases such as trypsin and chymotrypsin which are vital for the digestion of proteins. Importantly, these enzymes are produced as proenzymes or zymogens to avoid autolysis, or the breakdown of the pancreas itself. + +The release of these enzymes by the pancreatic acinar cells is strictly regulated by hormones and neurochemicals. Cholecystokinin (CCK) released from the enteroendocrine cells in the duodenum cause the release of these enzymes. Moreover, acinar cells also respond to another hormone, secretin, by releasing bicarbonate-rich fluid which helps to neutralize the gastric acid in the duodenum. + +Dysregulation in the function of pancreatic acinar cells can lead to severe health issues, including pancreatitis, which is characterized by inflammatory damage to the organ due to the premature activation of digestive enzymes. +" DOI:10.1097/01.mog.0000239863.96833.c0|DOI:10.1038/nrgastro.2013.36|DOI:10.1016/0165-6147(89)90192-2|https://www.ncbi.nlm.nih.gov/books/NBK54134/ +132 CL:0002067 CL_0002067 "Type A enteroendocrine cells, also known as alpha cells or A cells, are a species of endocrine cells primarily located in the pancreatic islets of Langerhans; they have also been identified within the lining of the stomach. Functionally, these cells are pivotal in glucose metabolism and homeostasis, accounting for about 20% of the total population of cells in the pancreatic islets. +The primary role of type A enteroendocrine cells involves the synthesis, storage, and secretion of the peptide hormone glucagon, which is critical in energy regulation throughout the body. In response to a decrease in blood glucose levels, the pancreatic A cells are stimulated to secrete glucagon into the bloodstream. Glucagon acts on its target cells, mainly in the liver, to stimulate glycogenolysis and gluconeogenesis processes, thereby increasing blood glucose levels back to normal. In this way, pancreatic A cells play an integral role in maintaining glucose homeostasis and preventing hypoglycemia. + +Pancreatic A cells also participate in the local regulation of islet activities as glucagon acts through glucagon receptors on A, B and D type cells within the islets. Recent studies have also shown that Pancreatic A cells play a role in the generation and regeneration of B type cells. Following beta cell injuries pancreatic A cells increase in numbers and produce Glucagon-like peptide-1 (GLP-1), which increases the proliferation and cytoprotection of beta cells. In response to extreme injury of B type cells pancreatic A cells can transform (transdifferentiate) into functioning B type cells. + +Until recently, glucagon has been considered a pancreas-specific hormone; however, extrapancreatic glucagon has been reported in patients who had undergone complete, and glucagon-positive cells been identified in the human stomach, indicating that Type A enteroendocrine cells are not restricted to the pancreas. +" DOI:10.2337/db15-1541|DOI:10.1016/j.diabres.2018.06.013|DOI:10.2337/dbi19-0002|DOI:10.3389/fphys.2012.00349/full|DOI:10.1210/en.2016-1748 +133 CL:0002075 CL_0002075 "The brush cell of the tracheobronchial tree is a specialized type of epithelial cell situated in the lung's airways system. Characterized by their visually distinguishable brush-like apical surface, brush cells (also called tuft cells) are given their name due to the tuft of microvilli protruding into the lumen of the respiratory tract. The high electron density and presence of a prominent tubulovesicular system in the apical cytoplasm are other defining microscopic features. + +The primary function of brush cells is chemosensation within the tracheobronchial system, including the trachea, bronchi and bronchioles. They have been identified as the pulmonary equivalent of taste receptor cells, acting as solitary chemosensory cells that serve as the primary line of defense and alarm signal against hazardous inhaled substances. Brush cells in the tracheobronchial tree express taste receptors and a taste transduction machinery which allow them to detect specific chemical signals from bacteria or environmental toxins and signal a downstream response such as protective reflexes like coughing and increased mucus secretion. + +Brush cells also act as physical barriers to help filtrate and clean the inhaled air, thus making an essential contribution to setting up the so-called mucociliary escalator. The tubulovesicular system within brush cells likely plays a role in transcytosis, which involves the movement of various substances across the epithelial barrier. Overall, the brush or tuft cells form an integral part of the airway's innate immune system, helping maintain a healthy and functional tracheobronchial tree. +" DOI:10.1164/rccm.200502-203WS |DOI:10.1073/pnas.101941810|DOI:10.1186/s12931-023-02570-8 +134 CL:0002097 CL_0002097 "Cortical cells of the adrenal gland, or adrenal cortical cells, are essential components of the endocrine system found in the adrenal cortex, the outer region of the adrenal gland. They are responsible for the synthesis and secretion of vital hormones, including glucocorticoids, mineralocorticoids, and small amounts of adrenal androgens. + +The adrenal cortical cells are further subdivided into three groups based on their position and function: zona glomerulosa, zona fasciculata, and zona reticularis. The zona glomerulosa cells are scattered and primarily secrete mineralocorticoids such as aldosterone; the zona fasciculata contains large adrenal cortical cells replete with liquids (“clear cells”) that release glucocorticoids; and the zona reticularis contains “compact” cells containing lipofuscin that are involved in the secretion of adrenal androgens. Each layer plays a distinct and vital role in maintaining a range of body functions, from metabolic processes to stress response mechanisms. + +The primary function of these cells corresponds to the hormones they produce. Glucocorticoids, such as cortisol, play a crucial role in glucose metabolism, immune response modulation, and stress response. Mineralocorticoids, primarily aldosterone, actively participate in maintaining the body's electrolyte and water balance by regulating sodium and potassium levels. Meanwhile, adrenal androgens serve as precursors for other sex hormones in both males and females. Therefore, adrenal cortical cells are a central part of the endocrine system, coordinating multiple vital physiological processes. +" DOI:10.1152/ajpendo.00100.2011|DOI:10.1016/j.steroids.2009.09.002|DOI:10.1038/s41574-021-00491-4|https://www.ncbi.nlm.nih.gov/books/NBK537260/|https://www.ncbi.nlm.nih.gov/books/NBK278945/ +135 CL:0002149 CL_0002149 "The epithelial cells of the uterus include different types of cells that play a critical role in reproductive biology, depending on their location within the uterus. The innermost layer of the uterus, known as the endometrium, is constituted of a single layer of luminal epithelial cells, which line the cavity of the uterus, and of columnar glandular epithelial cells, which form tubular glands that reach deeply into the endometrial stroma. + +The primary function of endometrial epithelial cells is to respond to hormonal signals, such as estrogen and progesterone, during the menstrual cycle. These cells undergo characteristic changes in response to cyclic variations in female hormones. During the proliferative phase of the menstrual cycle, rising levels of estrogen stimulate endometrial epithelial cells to proliferate and thicken the endometrium. Following ovulation, in the secretory phase, progesterone secretion triggers differentiation of these cells into a secretory phenotype, which drives preparation of the uterine lining for potential embryo attachment. These secretions are important for embryonic nutrition in the period between implantation and the establishment of the placental circulation. + +Furthermore, communication between the endometrial epithelial cells and the implanting embryo is a critical aspect of successful implantation. The epithelial cells express particular adhesion molecules, cytokines, and growth factors, which facilitate the attachment and invasion of the embryo into the uterine wall. In addition to their role in fertility, changes in these cells can lead to conditions such as endometriosis and endometrial cancer, both of which involve abnormal growth and division of endometrial epithelial cells. + +Other epithelial cells in the uterus include secretory epithelial cells in the cervix, the lower part of the uterus that connects to the vagina. These cells produce mucus, which changes in consistency and composition throughout the menstrual cycle and plays a crucial role in regulating sperm transport and providing a barrier to pathogens, thereby helping to prevent infection. In addition, epithelial cells in the myometrium, a muscular layer of the uterus responsible for contractions during labor and menstruation, help coordinate uterine contractions. +" DOI:10.1016/j.biocel.2012.10.012|DOI:10.1093/humupd/dml004|DOI:10.1016/j.tem.2019.11.008|DOI:10.1073/pnas.1915389116|DOI:10.1016/j.isci.2021.102258 +136 CL:0002145 CL_0002145 "Ciliated columnar cells of the tracheobronchial tree compose the inner lining of the tracheobronchial tree, the system of airways consisting of trachea, bronchi and bronchioles that allow passage of air into the lungs, where gas exchange occurs. A defining feature of these endo-epithelial cells are the tiny hair-like structures covering their surface, known as cilia. The nucleus is located at the base of the cell, and the area above it is rich in mitochondria and well-developed endoplasmic reticulum, both crucial for the energy-intensive process of cilia operation. + +The primary function of these ciliated cells is to keep the respiratory tract clean via mucociliary clearance or the respiratory escalator. These cells create a two-layered 'coat': The lower ""sol"" layer is watery where the cilia can beat in coordinated waves, and the upper ""gel"" layer is thick and sticky, trapping inhaled particles, such as dust, bacteria, viruses, and other potentially harmful substances. This rhythmical beating of the cilia then moves the mucus and trapped particles upwards and out of the respiratory tract, which is then either coughed out or swallowed. + +Damage or dysfunction of these ciliated cells, as seen in diseases such as primary ciliary dyskinesia, cystic fibrosis, or chronic bronchitis, may lead to reduced or ineffective mucociliary clearance and an increased susceptibility to respiratory infections." DOI:10.1101/cshperspect.a028241|DOI:10.1152/ajplung.00329.2019|DOI:10.1159/000196486|DOI:10.1146/annurev-physiol-021014-071931 +137 CL:0002188 CL_0002188 "Glomerular endothelial cells are specialized fenestrated cells located in the kidney, specifically in the glomerulus which is a network of tiny blood vessels. These cells are crucial to the multilayered structure of the glomerular filtration barrier, which serves a critical filtration function in the kidney. Glomerular endothelial cells are characterized by fenestrations or pores in their structure and exhibit an intrinsic sieving property, allowing free passage of water and small solutes while restricting large proteins and cells. + +The primary function of glomerular endothelial cells is to manage blood filtration to form urine. They are instrumental in maintaining the balance between substances that need to be excreted from the body, such as waste products, and those that need to be retained, like blood cells and essential macromolecules. Therefore, any dysfunction in these cells can lead to serious kidney conditions affecting the filtration barrier, causing proteinuria – abnormal presence of protein in urine – and progressive loss of kidney function. + +Moreover, glomerular endothelial cells contribute to preserving the structural integrity of the glomerular capillaries due to their distinct physical interactions with both the basement membrane and podocytes, cells lining the outermost layer of the glomerular filtration barrier. They secrete essential factors that influence the function and viability of other cells in the glomerulus. Various growth factors and cytokines also modulate the function of glomerular endothelial cells, indicating bidirectional communication between these different cellular elements. +" DOI:10.1152/ajprenal.90601.2008|DOI:10.1152/physrev.00055.2006|DOI:10.1038/s41573-021-00242-0|DOI:10.1152/ajprenal.2000.278.2.F173|DOI:10.1681/ASN.2005080810 +138 CL:0002203 CL_0002203 "The brush cells of the epithelium proper of the large intestine are one of the primary types of cells that constitute the epithelial lining of the large intestine. Brush cells (also called ‘tuft cells’) are often identified by their characteristic ‘brush border’, a thick layer of microvilli on their apical surface, which gives them a brush-like appearance under the microscope. This unique structure aids in the critical functions of these cells, which serve as sentinels monitoring intestinal content in the gastrointestinal tract. + +Brush cells are distinctive not only for their morphology but also for their role in the immune response of the gut. They play an important function as chemosensory cells, capable of detecting parasitic infections, and initiating an immune response. Intestinal brush cells express taste receptors on the apical surface that allow them to detect changes in the luminal environment, which in turn modulates gut function. They accomplish this by producing and secreting cytokines, in particular interleukin-25 (IL-25), which help alert the immune system to the presence of foreign bodies and set off a chain of immune responses. + +Intestinal brush cells in mice have been shown to be of particular importance during anti-helminthic and anti-protozoan immune response, while alterations of intestinal brush cell populations have been associated with intestinal diseases such as inflammatory bowel disease and coeliac disease. + +" DOI:10.3389/fimmu.2022.822867|DOI:10.1371/journal.ppat.1010318|DOI:10.1152/ajpgi.00073.2017 +139 CL:0002204 CL_0002204 "Brush cells, also referred to as tuft cells or multivesicular cells, are a specialized type of epithelial cell mainly noted for their characteristic 'brush border' composed of microvilli. These cells reside in the epithelial lining of tissue organs such as the respiratory tract, gastrointestinal tract, and the bile ducts. The name derives from their distinct appearance under the microscope, which resembles a brush due to the dense layer of microvilli protruding into the lumen. + +A key function of brush cells is chemosensation: They express a variety of signaling molecules and receptors that enable them to detect specific chemical stimuli in the environment and act as sensory transducers. Many of these receptors are responsive to luminal content, which makes brush cells vital for regulating and coordinating appropriate physiological responses to changes in these substances. + +Recent research has also elucidated an important role for these cells in immunity. Intestinal brush cells have been found to be the source of a cytokine called interleukin-25, which can initiate type 2 immune responses during parasitic infections. This immune function, along with the chemosensing abilities, signifies that brush cells could serve crucial roles in health and disease, although much research is still required to fully elucidate their myriad roles in physiology and pathology. Overall, brush cells are a versatile cell type, whose distinct morphology and functional capabilities allow them to perform a unique set of functions within the body. + +" DOI:10.1111/j.1469-7580.2005.00403.x|DOI:10.1007/978-3-211-99390-3_83|DOI:10.5114/ceji.2022.124416|DOI:10.1038/nature16161|DOI:10.3389/fphys.2015.00087 +140 CL:0002207 CL_0002207 "The brush cell of the trachea is a specialized cell type located predominantly in the epithelial lining of the trachea. Brush cells, also called tuft cells, are named for their distinctive morphology - a broad base leading to a narrower apex, adorned with a tuft of rigid, long microvilli resembling a brush. The cells are columnar and among the smallest in the respiratory tract, yet their appearance sets them apart from the typical ciliated cells that make up the majority of the tracheal epithelium. + +Brush cells are believed to serve a role as chemosensory sentinels in the trachea, monitoring the biochemical environment. The ‘brush’ or ‘tuft’ serves a critical purpose in heightening the cell's sense of contact with its surroundings. Brush cells of the trachea are equipped with taste receptors and a taste transduction machinery, such as the cation channel TRPM5 (transient receptor potential melastatin 5). Following activation through bitter-taste receptors, brush cells initiate downstream signaling to sensory neurons which then leads to protective respiratory nerve reflexes. + +Recent research has also shown that tracheal brush cells not only detect pathogenic substances but also contribute to the antimicrobial host defense by releasing neuropeptides that ultimately direct an influx of innate immune cells. +" DOI:10.1164/rccm.200502-203WS|DOI:10.1172/JCI161439|DOI:10.1164/rccm.200502-203WS +141 CL:0002208 CL_0002208 "Brush cells of the bronchus, also known as bronchial brush cells or tuft cells, are specialized epithelial cells found in the respiratory tract, specifically within the bronchi. These are called 'brush cells' due to their distinctive appearance, characterized by their apical surface being enveloped by a dense collection of long, thin, rigid microvilli, often likened to bristles of a brush. Some sources also describe them as having a bottle-like shape, with an enlarged middle section that narrows towards the base. + +The primary function of brush cells in the respiratory tract is chemosensation. They have the built-in capacity to sense changes in their chemical environments. Brush cells of the bronchi are equipped with a host of sensory receptors, including bitter-taste receptors, which allow them to detect and respond to a wide array of airborne substances. Several studies also indicate the potential roles these cells play in initiating signal transduction pathways that regulate local airway behaviors such as bronchoconstriction, mucus secretion and immune responses. + +Recent research also suggests that brush cells of the bronchus could potentially play a role in immune surveillance. They might can react to harmful pathogenic invasions in the airway by releasing certain compounds that aid in attracting immune cells to the site of infection. An increase in the number of brush cells has also been reported in certain lung diseases, suggesting a possible involvement in pathological processes. Although the precise role of bronchial brush cells continue to be the subject of ongoing research, they contribute to maintaining the overall integrity and function of the bronchial epithelium. + +" DOI:10.1164/rccm.200502-203WS|DOI:10.1172/JCI161439|DOI:10.1186/s12931-023-02570-8 +142 CL:0002225 CL_0002225 "Secondary lens fibers are a specialized type of elongated cells located within the structure of the eye's lens. They play an essential role in vision by enabling light transmission and focus on the retina, which allows for clear, distinct vision. These cells are characterized by their lack of nuclei and organelles, their orderly alignment, and their high protein content, particularly crystallins. + +Lens fibers are differentiated from equatorial epithelial cells of the lens in a process that involves cell elongation, denucleation and tight packing, which serve to reduce light scattering occurrences in the eye. This differentiation accelerates substantially after birth in comparison to during embryogenesis and continues throughout life, contributing to the growth of the eye lens. Secondary lens fibers are specifically those cells that are newly differentiated and cover the old lens fiber core. This process also leads to the removal of light-obstructing cellular components, mainly nuclei and organelles, making these fibers transparent and ideal for their function. + +The fibers carry out their primary function of light refraction via a high concentration of specialized proteins known as crystallins, which form a gradient of refractive index together with the cytoplasm. This index manipulation facilitates precise light focus onto the retina. Secondary lens fibers also contribute to the lens's shape and biomechanical properties through intercellular interactions, particularly at the sutures where the ends of the fibers meet. Any disruption to secondary lens fibers can lead to vision problems, including cataracts, which is the clouding of the lens resulting from the aggregation of crystallin proteins. +" https://www.sciencedirect.com/topics/immunology-and-microbiology/lens-fiber|DOI:10.1016/j.biocel.2007.10.034|DOI:10.1016/B978-1-4377-1926-0.10005-0|DOI:10.1098/rstb.2010.0324|DOI:10.1136/bmjophth-2020-000459 +143 CL:0000731 CL_0000731 "Urothelial cells are a unique type of epithelial cell found lining the urinary tract system. They form the urothelium, a specialized, multi-layered epithelium that lines major portions of the urinary tract, including the renal pelvis, ureters, bladder, and the proximal part of the urethra. The distinct characteristic of urothelial cells is their ability to stretch and contract depending on the volume of liquid they contain - a feature that facilitates the essential role they play in maintaining the functionality and integrity of the urinary system. + +The primary function of urothelial cells is to provide an impermeable barrier to urine, preventing the toxic components present in the urine from seeping back into the body's bloodstream. The urothelium consists of a superficial umbrella cell layer, 1–2 layers of intermediate cells, and a basal cell layer. The umbrella layer is composed of large, mostly binucleated cells that are covered in an asymmetrical unit membrane, the uroplakin plaques. These plaques function to seal the apical membrane of the bladder from the toxic and highly variable contents of urine. The lipid bilayer structure of uroplakin plaques has an exceptionally high concentration of uroplakins that contribute to the barrier function of the urothelium. + +Beyond their mechanical function, urothelial cells also play a role in sensing and signaling changes in the urinary system. They express a number of sensor molecules or respond to thermal, mechanical and chemical stimuli and can release chemical mediators. This allows them to act as sensory transducers because they detect changes in the filling state of the bladder and transmit this information to the nervous system. Moreover, these versatile cells contribute to the defense mechanism against urinary tract pathogens. They respond to bacterial infections by releasing chemical messengers, cytokines and chemokines, to attract immune cells, and also can engulf pathogens via endocytosis. + +" DOI:10.1152/physrev.00041.2019|DOI:10.1038/ki.2009.73|DOI:10.1038/ncpuro0672|DOI:10.1038/s41579-020-0324-0|DOI:10.1002/nau.22195 +144 CL:0002231 CL_0002231 "Epithelial cells of the prostate, also known as prostatic epithelial cells, are specialized cells found in the prostate gland, which surrounds the male urethra beneath the bladder. They play a crucial role in forming the acini and ducts of the gland's structure. The prostate's epithelium has multiple layers, including basal, luminal, and neuroendocrine cells; the luminal layer is composed of columnar epithelial cells, and the basal layer is composed of cuboidal epithelial cells. + +Prostatic epithelial cells primarily aid in the production and secretion of prostatic fluid, a critical component of semen. This fluid, which accounts for around 20-30% of semen volume, serves several key functions related to fertility. The prostatic fluid is alkaline in nature that aids in neutralizing acidic vaginal secretions, promoting the survival of sperm in the female reproductive tract. It also contains proteolytic enzymes that, upon ejaculation, lead to the liquefaction of semen, enhancing the motility of sperm. + +Additionally, prostate epithelial cells are involved in the secretion of prostate-specific antigen (PSA), a kallikrein-like serine protease, which is a normal component of the seminal plasma further aids in semen liquefaction. + +Prostatic epithelial cells are also linked to conditions like benign prostatic hyperplasia, which involves abnormal cell growth, and prostate cancer, which originates from prostatic epithelial cell transformations, especially in the peripheral zone. Consequently, these cells are key focal points in understanding and treating prostatic conditions and malignancies. +" DOI:10.1016/j.celrep.2018.11.086|DOI:10.1038/s41598-019-40820-2|DOI:10.1038/onc.2012.541|DOI:10.1159/000496289 +145 CL:0002328 CL_0002328 "The bronchial epithelial cells form the inner lining of the bronchial tubes, which are a key part of the respiratory system. These cells can be functionally and morphologically classified into three principal categories: basal, ciliated and secretory cells, each with specific adaptations that allow them to play a role in transport processes, immune barrier functions, and regeneration. + +Basal epithelial cells in the bronchi have an important role in cell adhesion and produce various bioactive molecules, such as cytokines. They also play a key role in maintaining the bronchial epithelium as they are able to self-renew and differentiate into other epithelial cell types, a function that is also critical after epithelial injury. + +The bronchial secretory cells (goblet cells) play an important role in producing mucus that traps foreign particles, including pathogens and toxins, in the airway lumen. The most abundant cell type within the bronchi are ciliated epithelial cells, which are characterized by a large number of cilia on the cell surface and high numbers of energy-producing mitochondria adjacent to their apical surface. Via directional beating of their cilia, these cells clear the particles that are trapped in mucus out from the airways. + +Some bronchial epithelial cells also behave as complex immune-sensing barriers. When intruders such as bacteria or viruses invade, these cells can identify them, triggering an immune response via the activation of the body's innate immune system. Moreover, these cells produce antimicrobial peptides and proteins which can kill or impede harmful microbes directly. +" DOI:10.1111/resp.12542|https://www.sciencedirect.com/topics/medicine-and-dentistry/bronchial-epithelium|DOI:10.1038/s41577-020-00477-9|DOI:10.1513/pats.200805-041HR|DOI:10.1152/ajplung.00319.2015 +146 CL:0002327 CL_0002327 "Mammary gland epithelial cells, also known as mammary epithelial cells, are essential cell types in the tissue of mammary glands, which are milk-producing glands in female mammals. They can be categorized into two types: luminal epithelial cells and myoepithelial cells, each with their distinct functions in milk processing and delivery. + +Luminal epithelial cells, which are located in the inner layer of the mammary gland ducts and alveoli, play a vital role in the secretion of milk proteins and lipids to form milk during lactation. These cells contain well-developed secretory apparatus, including rough endoplasmic reticulum and Golgi complex, facilitating the synthesis and secretion of milk proteins. Luminal epithelial cells express markers, like cytokeratin 8 and 18, and hormone receptors, such as estrogen and progesterone receptors, which play a crucial role in regulating the cell proliferation during the mammary gland development and lactation. + +Myoepithelial cells, on the other hand, are contractile cells situated between the luminal epithelial cells and the basal lamina in the ducts and alveoli of the mammary gland. They express markers such as smooth muscle actin and p63. One of their chief functions is the contraction during lactation, which aids in the expulsion of milk from the alveoli into the ductal network. Additionally, myoepithelial cells play a role in shaping the mammary gland ductal system and initiating the involution process after weaning. + +The homeostasis and functionality of the mammary epithelial cells are sensitive to hormonal regulation and surrounding microenvironment cues. Any abnormalities in these two types of mammary epithelial cells could disrupt the mammary gland function and potentially prompt the development of breast diseases, including cancer." DOI:10.1101/gad.242511.114|DOI:10.1038/s41574-022-00742-y|DOI:10.1083/jcb.200107065|DOI:10.1016/j.isci.2021.102413|DOI:10.3390/ijms23073883 +147 CL:0002329 CL_0002329 "The basal epithelial cells of the tracheobronchial tree are critical components found in the lining of the airway passages, including the trachea and bronchi. They are keratin-5-positive, nonciliated, cuboidal cells and typically tightly attached to the basement membrane. In humans, the proportion of basal cells in the respiratory epithelium gradually decreases going down the tracheobronchial tree: they represent approximately 34% of the cells in the trachea, 27% in the large airways, and 10% in the small airways, although it is worth noting that there are differences in the compositions of the tracheobronchial epithelia between different species. + +Basal epithelial cells serve as the basal layer of the tracheobronchial epithelium, providing both structural and regenerative support for the epithelial tissue that lines the upper regions of the respiratory tract. They serve as progenitor or stem cells that are capable of differentiating into multiple cell types, such as ciliated and secretory cells. This gives them a central role in homeostatic maintenance of the epithelium, and in repairing damaged epithelium after an injury or during disease. This regenerative capacity is crucial in maintaining the integrity of the tracheobronchial surface, especially given its continual exposure to inhaled irritants and microorganisms. + +In addition to their primary restorative function, basal epithelial cells are also involved in the initial immune response within the tracheobronchial tree. Equipped with pattern recognition receptors, these cells can identify and respond to pathogenic organisms, triggering an immune response and producing a range of inflammatory mediators, such as cytokines and chemokines, to help combat infections. +" DOI:10.1165/rcmb.2013-0049OC|DOI:10.1186/s12931-014-0160-8|DOI:10.2353/ajpath.2010.090870 +148 CL:0002332 CL_0002332 "The ciliated cell of the bronchus is a specialized type of epitheliali cell found in the lining of the bronchus, which is part of the tracheobronchial tree. These cells are characterized by the presence of hair-like structures called cilia on their surface. The primary function of these cilia is the active transport of mucus and trapped particles out of the respiratory tract. + +Ciliated cells of the bronchus form a crucial part of the body's innate defensive mechanism: They function as a barrier and play a key role in the mucociliary clearance mechanism - the coordinated, wave-like movement of the cilia that sweeps pathogens and particles trapped within the mucus in the airways, upward and out of the lungs, either to be swallowed or expelled by coughing. By doing so, these cells are crucial for preventing the lodging of pathogens deep in the lungs and hence reduce the risk of respiratory infections. + +In conditions affecting the respiratory tract, including chronic obstructive pulmonary disease (COPD) and asthma, the normal functioning of the ciliated cells may be compromised. For instance, the cilia may become impaired or destroyed due to exposure to harmful substances such as cigarette smoke, which can hinder the process of mucus removal, leading to a build-up of mucus and increased susceptibility to infection." DOI:10.1101/cshperspect.a028241|DOI:10.1146/annurev-physiol-021014-071931|DOI:10.1111/resp.12542 +149 CL:0002340 CL_0002340 "Luminal cells of the prostate epithelium are secretory cells in the prostate gland, which is located around the urethra at the base of the bladder. In addition to luminal epithelial cells, the adult prostate contains basal epithelial cells and rare neuroendocrine cells, organized as a pseudostratified epithelium surrounded by stromal cells. The main function of the prostate is to nourish and protect sperm by secreting a slightly alkaline fluid which makes up approximately 30% of the semen. + +The luminal epithelial cells form a single-layer lining in the prostate's acini. They have a polarized structure with the basal side attached to the basal lamina and the apical side facing the lumen. Specialized microvilli-like structures on the apical side aid in product secretion. Luminal cells express androgen receptors, making them sensitive to androgenic stimulation, which is crucial for regulating prostatic secretions and overall gland function. + +The prostate's Luminal cells are responsible for producing and releasing prostatic fluid, which supports sperm post-ejaculation. They synthesize key proteins like prostate-specific antigen (PSA) and prostatic acid phosphatase. + +Luminal cells are also a focus of prostate cancer research as they are the putative cells-of-origin for the majority of prostate cancers. Overproliferation and persistent damage can lead to the initiation of carcinogenic events within these cells. The PSA produced by luminal cells is also a key biomarker for diagnosing, monitoring, and treating prostate cancer. As such, understanding the health and disease-related functions of these cells is essential for managing prostate conditions. +" DOI:10.1016/j.trecan.2018.09.003|DOI:10.1016/j.celrep.2014.08.002|DOI:10.1016/j.cell.2014.08.017 +150 CL:0002341 CL_0002341 "Basal cells of the prostate epithelium are one of the major cell types found in the glandular part of the prostate, which is a small, walnut-shaped gland that produces seminal fluid in males. These cells are located at the base of the prostatic acinar epithelial layer and form a contiguous layer separating the acinar lumen, where the prostatic secretions coalesce, and the underlying connective tissue. In contrast to the luminal cells, basal cells lack secretory granules. In common with basal epithelial cells in other epithelia, prostatic basal cells express markers such as cytokeratin 14 and p63. + +A key function of the basal cells of the prostate epithelium is to provide structural support to the secretory luminal cells and contribute to maintaining the integrity of the epithelial layer. They also have unique regenerative properties that aid in the recovery of the glandular epithelium after injury. Under normal conditions, these cells remain quiescent, but upon injury, they proliferate to replace the damaged secretory luminal cells, indicating a stem/progenitor cell-like behavior. They also play an important role in serving as a reserve cell population helping in maintaining tissue homeostasis. + +Basal cells of prostate epithelium are also central to understanding the pathobiology of prostate diseases. They are typically absent in prostatic adenocarcinomas, the most common form of prostate cancer, but they are thought to play a critical yet complex role in oncogenesis and therapeutic resistance mechanisms of prostate cancer, and in benign prostatic hyperplasia. They also have the ability to differentiate into neuroendocrine cells or luminal cells under certain conditions, contributing to disease heterogeneity. +" "DOI:10.1080/15384101.2023.2206502|DOI:10.1016/j.celrep.2018.11.086|DOI:10.1242/dev.01384 +|DOI:10.1073/pnas.1320565110|https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219311/" +151 CL:0002368 CL_0002368 "Respiratory epithelial cells form the epithelium that lines the nasal cavity, trachea, and lungs. The respiratory epithelium consists of various specialized epithelial cells and its cellular composition differs depending on the location. The various cells are adapted for their specific functions in homeostasis, gas-exchange, air transport, and host defense. + +The surfaces of the so-called conducting airways (the nasal cavity, trachea, bronchi, and bronchioles) are lined by a pseudostratified columnar epithelium consisting of basal, ciliated, Clara (non-ciliated secretory cells), and goblet cells, as well as rare neuroepithelial cells. The main function of the ciliated epithelial cells is to move mucus (produced by goblet cells) which traps particles, including pathogens, up towards the throat for expulsion. + +Further along the tracheobronchial tree, the epithelium gradually changes. The bronchioles and respiratory acinar ducts are generally lined by a single columnar or cuboidal epithelium consisting mostly of ciliated cells and Clara cells. The epithelial surface of alveoli, where gas exchange takes place, is made up of extremely thin, squamous cells, allowing for easy diffusion of oxygen and carbon dioxide. + +The basal cells of the respiratory epithelium have a crucial regenerative function. They are the principal stem cells of the airways as they are able to differentiate into most other epithelial cell types. The basal cells are attached to the basement membrane by desmosomes; this location deep in the epithelium protects them from the external environment. They become activated in response to injury and provide rapid reconstitution of a fully differentiated epithelium. They also have a role in oxidant defense and (innate) immunity responses. + +Together the different epithelial cells in the respiratory epithelium are essential for maintaining a healthy respiratory system, serving as barriers and active participants in immune responses. +" DOI:10.1042/BCJ20220572|https://www.ncbi.nlm.nih.gov/books/NBK541061/#:~:text=The%20majority%20of%20the%20respiratory,that%20allows%20for%20gas%20exchange.|https://www.sciencedirect.com/topics/immunology-and-microbiology/respiratory-epithelium|DOI:10.1038/ni.3045|DOI:10.3389/falgy.2021.787128 +152 CL:0002370 CL_0002370 "The respiratory goblet cell is a highly specialized cell type found primarily within the respiratory tract, including the nose, trachea, and lungs. Named because their shape resembles a goblet - a drinking vessel with a wide body and narrow neck - these cells form a vital part of the respiratory system's protective mechanisms. They are found within the columnar epithelium lining these organs, which forms a barrier between the internal body and the exterior environment. + +A principal function of the respiratory goblet cell is the production and secretion of mucus, a carbohydrate-rich, viscous and gel-like substance that plays a critical role in trapping dust, bacteria, viruses, and other airborne particles that are inhaled. The mucus secreted by the goblet cells covers the lining of the respiratory tract, effectively catching these particles and preventing them from reaching the lungs and causing infection. Mucus also provides hydration and lubrication to the respiratory tract surfaces, which is important in maintaining the tissue's health and functioning. + +In addition to their mucus-secreting capabilities, respiratory goblet cells also play a significant role in the body's inflammatory responses. When the respiratory system is exposed to irritants or pathogens, the number and activity of goblet cells often increase, leading to a higher production of mucus. This is a protective response designed to trap and neutralize the harmful substances more effectively. However, in conditions like chronic obstructive pulmonary disease (COPD) and asthma, an overproliferation of goblet cells, also known as goblet cell hyperplasia, can lead to excessive mucus production and airway obstruction." DOI:10.1016/S1357-2725(02)00083-3|DOI:10.1165/ajrcmb.25.5.f218|DOI:10.2147/COPD.S38938|DOI:10.3109/01902148.2013.791733|DOI:10.1111/febs.15731 +153 CL:0002570 CL_0002570 "Mesenchymal stem cells of adipose tissue, also known commonly as adipose-derived stem cells (ADSCs), are a population of adult stem cells that can be obtained easily from adipose tissues. They have many of the same regenerative properties as other mesenchymal stem cells, but are more easily accessible than bone marrow-derived stem cells. + +Adipose-derived stem cells show immense promise in the field of regenerative medicine due to their ability to differentiate into adipocytes, chondrocytes, myocytes, osteoblasts, and other cell types. ADSCs also possess immunomodulatory and homeostatic functions: they have the ability to suppress immune responses and provide a therapeutic environment for tissue repair and regeneration, as well as supporting the proliferation of adipocytes and the overall expansion of adipose tissue and contributing to the tissue's ability to react to demands of energy storage and mobilization. Dysfunction of these cells may contribute to metabolic complications observed in obesity and diabetes. + +ADSCs have been used for therapeutic applications such as pathological wound healing, severe refractory acute graft-versus-host disease, and idiopathic thrombocytopenic purpura." DOI:10.1038/s41536-019-0083-6|DOI:10.1016/j.biopha.2019.108765|DOI:10.1016/j.tibtech.2006.01.010|DOI:10.1111/dgd.12049|DOI:10.1096/fj.202100332R +154 CL:0002586 CL_0002586 "Retinal pigment epithelial (RPE) cells form a single layer of cells at the back of the eye sandwiched between the neurosensory retina and the choroid, playing a significant role in maintaining vision health. These pigment-laden cells are highly specialized and perform an array of metabolic and transport functions essential for the maintenance of the photoreceptor cells (rods and cones) in the retina. The pigmentation of RPE cells actively aids in the absorption of excess light and the prevention of light scattering, thus enhancing the eye's optical properties. + +The retinal pigment epithelium forms a key part of the blood/retina barrier. The cells have long sheet-like microvilli on their apical membrane that project into the light-sensitive outer segments of the photoreceptors, forming a close structural interaction. The basolateral membrane of the RPE interacts with the underlying Bruch’s membrane, which separates the RPE cells from fenestrated endothelium of the choriocapillaris. + +RPE cells support the photoreceptor by providing them with oxygen and nutrients (such as glucose, retinol and fatty acids) and removing waste products. They also recycle the visual pigment, in a process called the ""visual cycle"", where the RPE cells play a vital role in the regeneration of visual pigment (11-cis retinol) following the absorption of light. This is essential for the maintenance of photoreceptor excitability. + +Beyond this, RPE cells take part in the phagocytosis process, where they digest the shed ends of photoreceptor outer segments, thus, preventing the build-up of waste residue that could otherwise harm retinal health. They also secrete various factors, including growth factors required to maintain the structural integrity of choriocapillaris endothelium and photoreceptors, as well as immunosuppressive factors that play an important role in establishing the immune privilege of the eye. + +" DOI:10.3389/fphar.2021.727870/full|https://www.sciencedirect.com/topics/chemistry/retinal-pigment|DOI:10.1152/physrev.00021.2004|DOI:10.1111/febs.16018 +155 CL:0002623 CL_0002623 "Acinar cells of the salivary gland are a critical part of the oral physiology and the digestive mechanism. These specialized cells are concentrated towards the terminal ends of the salivary glands, where they form sac-like acini or clusters. The primary function of these cells is to produce and secrete saliva. This substance, comprised mainly of water, electrolytes, mucins, and enzymes, is vital for the initial stages of digestion and for the regular maintenance of oral health. + +Acinar cells produce the two main types of saliva: serous and mucinous. Serous saliva contains the enzyme amylase responsible for the initial breakdown of complex carbohydrates and is predominantly produced by the parotid gland, the largest of salivary glands. The mucinous type, more common in the submandibular and sublingual glands, contains mucin that aids in lubrication, facilitating the process of mastication and bolus formation. + +Moreover, acinar cells also express and respond to various endocrine, paracrine, and autocrine hormones that govern the quantity and composition of the saliva produced. This implies sensitivity and modulation according to the internal and external environment, dietary habits, and even circadian rhythms. + +Impairment of acinar cells, whether due to damage or related to a systemic condition such as Sjögren's Syndrome, can disrupt the optimal functioning of the oral and digestive systems. In conclusion, acinar cells of the salivary gland have a substantial role in oral health and overall homeostasis. +" DOI:10.1111/prd.12116|DOI:10.1152/physrev.00011.2011|DOI:10.1038/sj.bdj.4807861|DOI:10.1016/S0140-6736(05)66990-5|https://www.ncbi.nlm.nih.gov/books/NBK538325/ +156 CL:0002633 CL_0002633 "Respiratory basal cells are highly specialized cells that serve a crucial role in the human airway epithelium, predominantly found lining the surfaces of the trachea and bronchi. These cells exhibit a distinctive columnar shape and are attached directly to the basal lamina. They are characterized by the presence of high amounts of cytoplasmic keratins, predominantly keratin 5 and 14, and transcription factor tumor protein (tp63), which set them apart from other types of lung epithelial cells such as ciliated cells and secretory cells. + +Basal cells are essential for maintaining airway integrity. They make up one third of all respiratory epithelial cells and serve as stem cells as they can transform into different cell types, like goblet cells, ciliated cells, and club cells, when needed for homeostatic maintenance of the epithelial barrier or to repair and restore a healthy cellular environment after injury. + +Their position at the interface between the internal environment and the external atmosphere makes these cells a first line of defense against air-borne irritants, allergens, and pathogens. Their robust, intrinsic reparative properties facilitate effective recovery from such adversities. However, damage to respiratory basal cells or abnormalities in their function are associated with several respiratory pathologies such as asthma, chronic obstructive pulmonary disease, and lung cancer. Therefore, understanding these cells' function, and their role in disease, is crucial for the development of new therapeutic strategies for respiratory disorders. +" DOI:10.3389/falgy.2021.787128|DOI:10.1186/s12931-022-02042-5|DOI:110.1038/s41385-020-00370-7 +157 CL:0002632 CL_0002632 "Epithelial cells of the lower respiratory tract line the trachea, bronchi, and bronchioles (the tracheobronchial tree), as well as the alveoli, and are crucial for defending against inhaled pathogens and foreign particles. The epithelium of the lower respiratory tract is composed of a heterogeneous population of specialized epithelial cells which serve several functions in respiratory physiology. + +The primary function of the respiratory epithelium is to form a physical barrier through tight junctions, preventing harmful substances from breaching this protective layer. A subset of secretory epithelial cells also produce mucus, which traps inhaled particles and pathogens, facilitating their clearance via coordinated movements of ciliated cells in a process called mucociliary clearance. Additionally, some of the epithelial cells actively participate in the immune response by recognizing and responding to pathogens, secreting antimicrobial peptides, and releasing cytokines that recruit and activate immune cells. + +Finally, specific epithelial cell types in the alveoli, known as type I and type II alveolar cells, have distinct roles. Type I alveolar cells, with their thin, flattened structure, facilitate efficient gas exchange between the airways and the bloodstream. In contrast, type II alveolar cells synthesize and secrete surfactant, a lipid-protein complex that reduces surface tension, preventing alveoli collapse and enhancing breathing mechanics. + +This balance between protection and function underscores the vital role of lower respiratory tract epithelial cells in maintaining overall respiratory system integrity, and there is growing evidence that disturbance in epithelial function is a driver of various chronic lung diseases. +" DOI:10.1038/mi.2017.71|DOI:110.1038/s41577-020-00477-9|DOI:110.1016/j.alit.2017.08.011|DOI:110.1042/BCJ20220572 +158 CL:0005006 CL_0005006 "Ionocytes are specialized cells predominantly found in the mammalian respiratory and renal systems as well as in the gills, skin, and intestinal tract of fish. These cells play crucial roles in maintaining ion and acid-base homeostasis. Ionocytes demonstrate remarkable plasticity and are able to adapt themselves in response to changes in environmental conditions such as pH, salinity, ion concentration, and temperature. + +These cells work by selectively absorbing specific ions from the environment, thus maintaining the body's internal ionic balance. The most commonly absorbed ions include sodium (Na+), chloride (Cl-), calcium (Ca2+), and hydrogen (H+). Moreover, ionocytes contribute to acid-base regulation. In response to acidosis or alkalosis, ionocytes can either excrete or retain hydrogen (H+) and bicarbonate (HCO3-) ions to readjust the blood pH. Further, experimental evidence suggests a functional complexity of ionocytes, implying diverse roles beyond ion regulation. Recent research highlights ionocytes' involvement in ammonia excretion and the regulation of extracellular fluid volume, highlighting their contribution to the overall homeostatic process. + +Malfunctioning ionocytes have been implicated in various diseases, including cystic fibrosis which is caused by mutations in the chloride channel CFTR, an ionocyte marker. +" DOI:10.1146/annurev-pathol-042420-094031|DOI:10.1016/j.jcf.2019.09.010|DOI:10.1038/s41586-018-0393-7|DOI:10.1038/s41598-023-30603-1|DOI:10.3389/fmars.2020.00709 +159 CL:0005012 CL_0005012 "The multi-ciliated epithelial cell are terminally differentiated epithelia that line brain ventricles, the respiratory tract and parts of the female and male reproductive organs in animals, playing critical roles in the maintenance of homeostasis through ciliary motion. They are characterized by the presence of hundreds of motile cilia, hair-like microtubule-based organelles that beat in a coordinated fashion to direct fluid flow over the cell surface. + +Multi-ciliated epithelial cells have fundamental roles in the proper functioning of many organ systems. In the respiratory system, they line the airways and orchestrate the coordinated movement of mucus, effectively clearing the airways of inhaled particles and pathogens. These cells are also vital in the ventricular system of the brain where they facilitate cerebrospinal fluid circulation, thus contributing to the maintenance of the brain's microenvironment. In the fallopian tube, multi-ciliated epithelial cells aid in the transport of oocytes from the ovary to the uterus, a process crucial to reproduction. + +The formation and function of multi-ciliated epithelial cells is a highly regulated process that involves several stages of development including cell specification, centriole multiplication, and ciliogenesis. Any disruption in these processes can result in dysfunctional or decreased numbers of cilia, which can lead to a myriad of health issues, ranging from chronic respiratory infections to infertility. " DOI:10.1016/j.cub.2014.08.047|DOI:10.1101/cshperspect.a028233|DOI:10.1038/nrm.2017.21 +160 CL:0009009 CL_0009009 "Paneth cells of the colon are specialized secretory epithelial cells that can be found in the large intestine, albeit in small numbers compared with the small intestine where Paneth cells are more abundant. Under disease conditions such as inflammatory bowel disease, Paneth cells increase in numbers in the colon. They reside in the crypts of Lieberkühn, which are glandular structures embedded within the mucosal layer of the small and large intestine. + +Paneth cells play a crucial role in maintaining intestinal homeostasis and acting as a frontline of defense in our bodies against ingested microbes. They achieve this through the secretion of antimicrobial peptides and proteins such as lysozyme and defensins, which can directly kill or inhibit the growth of various bacteria, fungi, and viruses. They degranulate these substances into the intestinal lumen, especially under conditions of pathogenic invasion or damage to the epithelial lining. + +Moreover, Paneth cells are essential for the maintenance of intestinal stem cells, which continually replace the epithelium of the intestine. They create a niche for these stem cells at the base of the crypts, secreting various signaling molecules and factors that are essential for the growth and differentiation of intestinal stem cells. In essence, the existence and function of Paneth cells are fundamental to the overall gut health and immune defense system, by providing both antimicrobial functions and a conducive environment for the renewal of the intestinal lining. + +The role of Paneth cells specifically in the colon is of interest in the context of inflammatory bowel disease, such as ulcerative colitis and Crohn’s disease: Their presence in the colon is thought to represent Paneth cell metaplasia and indicates a chronic inflammatory state. +" DOI:10.1038/nrmicro2546|DOI:10.1038/nature09637|DOI:10.1136/gut.48.2.176|DOI:10.1093/ecco-jcc/jjac190.0884|DOI:10.1002/ibd.20197 +161 CL:0009006 CL_0009006 "The enteroendocrine cell of the small intestine is a specialized type of cell that forms part of the lining of the intestinal wall. These cells are interspersed among absorptive cells, mucus-secreting goblet cells, and other gut cell types, forming the crypt-villus axis, which is the functional unit of the small intestinal epithelium. + +Functionally, enteroendocrine cells play a pivotal role in the gut-endocrine system, which is responsible for the digestive process. These cells translate the luminal nutrient status into hormonal signals thereby acting as chemosensors. They contain secretory granules at their base which release hormones into the bloodstream following chemo-sensation. The hormones they secrete perform diverse functions including regulating gastric secretion, gut motility, insulin release, appetite control and other local and systemic effects. + +In addition to their endocrine functions, enteroendocrine cells also play a part in the modulation of the immune response in the gut. They can secrete cytokines and chemokines that have a role in directing the immune response to invading pathogens. Moreover, emerging research suggests that these cells play a role in maintaining the balance between gut resident bacteria, known as the gut microbiota, and the host. As such, a comprehensive understanding of the enteroendocrine cells of the small intestine underpins knowledge in nutrition, endocrinology, and various gastroenterological conditions. +" DOI:10.1146/annurev-physiol-021115-105439|DOI:10.1111/j.1365-2613.2011.00767.x|DOI:10.1038/mi.2017.73|DOI:10.1016/j.coph.2013.09.008|DOI:10.1038/nature24489 +162 CL:0009016 CL_0009016 "The intestinal crypt stem cells of the large intestine are a specialized type of self-renewing cells that are responsible for continuously replenishing the cell population of the large intestine. This regeneration is critical for the maintenance of regular functions of the large intestine which includes absorption of water and electrolytes, and facilitating fecal elimination. These intestinal crypt stem cells are located at the bottom of the crypts of Lieberkühn, which are small glandular structures located along the entire length of the intestine's lining; they reside in a specialized niche that provides both physical protection and specific signals for stem cell maintenance, thus playing an imperative role in the architecture of the intestinal lining. + +Intestinal crypt stem cells possess the unique property of continuous self-renewal through a process of asymmetric cell division: each time an intestinal crypt stem cell divides, it produces two daughter cells: one progresses toward differentiation to replace functionally specialized cells in the intestinal lining, such as absorptive cells and secretory cells (including goblet cells, enteroendocrine cells, and Paneth cells), while the other retains stem cell properties ensuring a constant stem cell population. The balance between self-renewal and differentiation by intestinal crypt stem cells is essential for maintaining intestinal homeostasis. + +Moreover, the function of intestinal crypt stem cells is greatly influenced by intricate signaling pathways and interactions with other cell types in the crypt niche. For instance, Wnt and Notch signaling pathways crucially regulate their proliferation and differentiation state. Dysregulation of these signaling pathways, or damage to the intestinal crypt stem cells, may lead to several gastrointestinal diseases, including cancer. Thus, the understanding and further research on the intestinal crypt stem cells is largely linked to not only maintaining gut health but also evolutionary knowledge of tumorigenesis and regenerative medicine." DOI:10.1038/s41575-018-0081-y|DOI:10.1101/gad.1674008|DOI:10.1073/pnas.231487198|DOI:10.1038/s41419-022-04607-0|DOI:10.15252/embr.201540188 +163 CL:0009042 CL_0009042 "Enteroendocrine cells of the colon are specialized secretory cells located within the lining of the colon section of the gastrointestinal tract. They form a significant part of the diffuse endocrine system, which consists of a wide array of cells that secrete hormones directly into the blood. These cells are integral to the functioning of the digestive system and influence a range of physiological processes in the body. The enteroendocrine cell population of the large intestine is generally less diverse than in the small intestine + +Enteroendocrine cells of the colon are responsible for the production and secretion of several gastrointestinal hormones that regulate various digestive functions. Different types of enteroendocrine cells in the colon release different hormones, including gastrin, secretin, cholecystokinin, glucose-dependent insulinotropic peptide (GIP), and glucagon-like peptides (GLP-1 and GLP-2). The secretion of these hormones is carefully regulated and occurs in response to specific stimuli such as the presence of food or changes in the internal environment of the gastrointestinal tract. These hormones have critical roles in regulating gut motility, stimulating pancreatic and biliary secretions, controlling appetite, modulating the immune response in the gastrointestinal tract, and maintaining glucose homeostasis. + +The function of these cells is not limited to hormone secretion. They also play a vital role in the colon’s sensing mechanisms. These cells act as chemosensors, detecting changes in the chemical composition of luminal content, including nutrient concentration and pH, and responding accordingly to maintain homeostasis. They are additionally involved in the regulation of the protective mucosal barrier by secreting bioactive factors that interact with the gut microbiota and immune cells. +" DOI:10.1111/j.1365-2613.2011.00767.x|DOI:10.1007/s00441-016-2530-7|DOI:10.1038/s41574-019-0168-8|DOI:10.1093/ibd/izz217 +164 CL:0009039 CL_0009039 "Colon goblet cells are a subset of intestinal goblet cells that are localized in the epithelial lining of the colon. They are specialized secretory epithelial cells that are recognized by their characteristic ‘goblet’ or flask-like shape and typically have a distinctive appearance due to the accumulation of secretory vesicles in their cytoplasm. + +The primary function of goblet cells is the secretion of mucus, which is an essential substance for the protection and successful functioning of the intestinal tract. In the colon, goblet cells continuously renew the inner mucus layer, which is attached and impervious to bacteria (the outer layer of the colon is unattached and is the habitat of commensal bacteria) + +The mucus secreted by goblet cells is rich in glycoproteins known as mucins, especially MUC2, forming a complex web of molecules that comprises the foundational structure of the mucus layer. It traps and eliminates harmful bacteria, while selectively allowing beneficial microbiota to access the epithelial surface and aid in digestion and nutrient absorption. The mucus layer not only provides a provides a protective barrier against pathogen invasion, as well as mechanical damage, and the erosive effects of digestive enzymes, it also acts as a lubricant to facilitate the passage of food material. + +Colon goblet cells are also involved in regulating the local immune response within the gut, maintaining the delicate balance between necessary immune reactions to harmful pathogens and tolerance to beneficial microbiota and dietary substances. Goblet cells can modulate immune responses by presenting antigens to dendritic cells, as well as through the production of immunomodulatory molecules that can alter the behavior of immune cells. When the inner mucus layer of the colon is defective, it might be a pathophysiological mechanism for colitis and infectious diseases. +" DOI:10.1038/mi.2015.32|DOI:10.1038/s41385-018-0039-y|DOI:10.1073/pnas.1006451107|DOI:10.1038/nrgastro.2013.35|DOI:10.1038/mi.2016.132 +165 CL:0009041 CL_0009041 "Tuft cells, also often referred to as brush cells or caveolated cells, are highly specialized sensory cells found in the colon, among other organs. They were named for their unique appearance under an electron microscope, which presents a distinctive ‘tuft-like’ morphology. They are characterized by apical microvilli, arranged in an irregular tuft that confers a dome-like shape. These cells comprise only a small fraction of the cells in the epithelial layer of the colon, making them among the least populous cell types in this region. + +Tuft cells in the colon primarily function as chemosensory cells that can sense and respond to environmental changes. These cells can detect and respond to microbial metabolites, helping initiate immune responses against potential threats. + +Recent studies have revealed that tuft cells play a role in responding to intestinal parasitic infections. When a gastrointestinal parasite infects the colon, tuft cells are activated and release the cytokine IL-25. This action increases the production of tuft cells and triggers essential Th2 immune responses to expel the parasites. Also, the removal of tuft cells has been linked to increased susceptibility to these infections. However, overactivity of tuft cells has been associated with inflammatory bowel disease, highlighting the need for a delicate balance of tuft cell function to maintain colon homeostasis. +" DOI:10.3389/fimmu.2022.822867|DOI:10.1371/journal.ppat.1010318|DOI:10.1152/ajpgi.00073.2017 +166 CL:0011004 CL_0011004 "Lens fiber cells are specialized, elongated cells located in the ocular lens, an important part of the eye responsible for focusing light onto the retina to create clear defined images. These cells are unique among body cells, as they are transparent and filled with a clear protein called crystallin to facilitate the passage of light. + +The entire life cycle of a lens fiber cell includes differentiation from lens epithelial cells, which are the progenitor cells lying at the anterior surface of the lens. In response to various signals, these cells elongate and migrate towards the posterior pole, while simultaneously undergoing a process of denucleation and degradation of cellular organelles. This unique process ensures that the cells do not scatter light, which is critical for the transparency of the lens. After reaching full maturity, lens fiber cells form tightly packed layers, known as laminae, to make up the distinctive architecture of the ocular lens. + +Lens fiber cells play pivotal roles in vision. Their primary function is to transmit and focus the light that enters the eye onto the retina, providing the sharpness and clarity necessary for vision. The precise alignment and organization of these cells allow for optimal light transmittance and minimizes scattering, thereby maintaining the transparency of the lens. As such, disruptions or abnormalities in lens fiber cells can lead to serious vision impairment, including conditions like cataracts, a common condition characterized by the opacification of the lens." DOI:10.1016/j.exer.2016.03.016|DOI:10.1242/dev.107953|https://www.sciencedirect.com/topics/immunology-and-microbiology/lens-fiber|DOI:10.1016/j.pbiomolbio.2003.11.012|DOI:10.1098/rstb.2010.0300 +167 CL:1000296 CL_1000296 "Epithelial cells of the urethra constitute the inner lining of the urethra, forming a mucosal barrier that helps protect the body from external contaminants. The type of epithelial cells found in the urethra can vary along its length. In general, the urethra is lined with stratified squamous epithelium in its distal or external portion, which is closer to the external environment. This type of epithelium provides protection against mechanical stress and pathogens. Closer to the bladder, the urethra transitions to a different type of epithelium. In males, the proximal part of the urethra is lined with pseudostratified columnar epithelium in the region where it passes through the prostate gland. In females, the transitional epithelium may be present in the proximal part of the urethra near the bladder. + +Epithelial cells of the urethra are primarily dedicated to the protection of underlying tissues from mechanical stress and pathogens during micturition (urination). They do this by creating a tight, impermeable barrier that prevents the entry and colonization of invading microbes. They produce a variety of antimicrobials and are tightly packed to prevent infiltration between cells, forming an integral part of the body's innate immune system. + +In addition to their protective role, these cells are involved in the secretion of mucus. This mucus acts as a lubricant that ensures the smooth and easy passage of urine from the bladder through the urethra and out of the body, reducing any potential damage from the erosive action of urine. Epithelial cells of the urethra are dynamic, constantly renewing their numbers to replace any cells lost through wear and tear. Any disruptions to the function or integrity of these cells may contribute to urinary tract infections and other urological disorders. +" DOI:10.1089/ten.teb.2016.0352|DOI:10.1038/s41385-022-00565-0|DOI:10.1101/2020.02.19.937615v2.full|DOI:10.1152/ajprenal.00327.2009|DOI:10.1016/j.celrep.2018.11.086 +168 CL:1000312 CL_1000312 "Bronchial goblet cells are a subset of goblet cells that are predominantly found in the respiratory tract, specifically within the bronchi and bronchioles. Named for their flask-like shape and their apparent similarity to a goblet, these cells contribute significantly to the maintenance of lung health and homeostasis. In humans, goblet cells comprise up to 25% of the bronchial epithelial columnar cells and are an integral part of the mucus-secreting system of the respiratory tract and are primarily responsible for the production and secretion of mucus. + +The mucus secreted by bronchial goblet cells serves as a protective layer over the delicate and sensitive structures of the bronchi. The mucus, an amalgamation of glycoproteins, lipids, and other substances, traps any inhaled dust, microorganisms, and pollutants, preventing them from reaching deeper lung tissues and causing potential damage. Additionally, the mucus secretion aids in moistening the airway surface, thereby facilitating effective gas exchange and maintaining the overall health of the respiratory tract. + +Bronchial goblet cells have an innate defense mechanism wherein they increase secretion of mucus in response to irritants, infection or inflammation in the airway. This strategy, however, if incessantly stimulated, can lead to airway obstruction and health complications like asthma and chronic obstructive pulmonary disease (COPD). +" DOI:10.1016/S1357-2725(02)00083-3|DOI:10.1016/S0165-6147(00)01600-X|DOI:10.1080/07853890600585795|DOI:10.2147/COPD.S38938 +169 CL:1000326 CL_1000326 "The ileal goblet cell is a subset of intestinal goblet cells that are a key component of the epithelium of the ileum, a portion of the small intestine. Goblet cells are named and characterized by their distinctive 'goblet' shape with a narrow base tapering to a broad apical surface; located between the lumen of the intestine and the internal environment of the body, they serve an integral role in maintaining gut homeostasis. + +Like all intestinal goblet cells, the primary function of ileal goblet cells is the production and secretion of mucins, large, heavily glycosylated proteins that combine to form mucus. This mucus lining serves as a protective barrier, shielding the underlying tissue from the potentially damaging effects of digestive enzymes, acids, or pathogenic microbes present in the gut lumen. Their strategic location in the ileal segment of the intestinal tract aids in efficient nutrient absorption while also maintaining an impregnable barrier against potential pathogens, ensuring an intricate balance. + +Goblet cells of the ileum also play a significant role in immune modulation. They are thought to promote oral tolerance (the immune unresponsiveness to orally ingested antigens such as food) by delivering luminal antigens to underlying dendritic cells, thereby driving immune education and tolerogenic responses. They also secrete bioactive molecules, such as the trefoil factor peptide TFF3, which aids in repairing damaged epithelium. By performing these crucial functions, ileal goblet cells not only aid in maintaining intestinal health, but also contribute significantly to the overall well-being of the organism. +" DOI:10.1038/s41575-022-00675-x|DOI:10.1007/s11894-010-0131-2|DOI:10.1038/nature10863|DOI:10.1111/imr.12182 +170 CL:1000320 CL_1000320 "The large intestine goblet cell is a highly specialized type of mucosal epithelial cell that is located within the epithelial lining of the large intestine. The key function of goblet cells is the production and secretion of a protective layer of mucus which is essential for maintaining gut homeostasis. Goblet cells have a characteristic 'goblet-like' shape, which adapts them for this specific function: organelles such as the nucleus, mitochondria, ER, and Golgi apparatus are located in the basal portion of the cell; while the vesicles with mucins (required for mucus production) are located apically, close to the apical membrane where their exocytosis takes place. + +The goblet cells of the large intestine produce a thick layer of mucus that coats the intestinal lumen. This mucus provides a barrier that prevents the direct contact of intestinal cells with bacteria and other potentially toxic substances present in the digestive tract. It also lubricates the intestine to facilitate the smooth passage of digested food material. It is worth noting that the mucus system differs between the small and large intestine: although in both the mucus is built around MUC2 mucin polymers produced by goblet cells, it is becoming clear that there are several types of goblet cells that function in different ways. + +From an immunological perspective, large intestine goblet cells participate in promoting a balanced gut immune response. They contribute to the process known as immune tolerance, where they prevent the body's immune system from overreacting to the trillions of bacteria present in the gut. These cells achieve this by secreting molecules that help maintain a calm environment, limiting inflammatory reactions unless absolutely necessary. Any dysfunction or decrease in the number of goblet cells can result in a compromised intestinal barrier leading to various health issues, including inflammatory bowel disease. +" DOI:10.1111/imr.12182|DOI:10.1146/annurev-physiol-021115-105447|DOI:10.1042/BSR20201471|DOI:full/10.1111/febs.15731|DOI:10.1038/mi.2015.32 +171 CL:1000329 CL_1000329 "Tracheal goblet cells are specialized cells found in the lining of the trachea. They are a key component of the tracheobronchial epithelium, a critical region responsible for maintaining open airways and preventing the ingress of harmful particles or irritants. Goblet cells are filled with membrane-bound secretory granules, which are responsible for their distinctive, goblet-like shape. + +Goblet cells specialize in the production and secretion of mucus, a slimy substance composed primarily of glycoproteins (mucins) and water. This sticky mucus serves to trap foreign particles and pollutants, such as dust, bacteria, and viruses that an organism breathes in. After trapping these particles, the cilia on neighboring ciliated epithelial cells beat synchronously, forming a coordinated escalator to push mucus upwards toward the pharynx, where it's either swallowed or expectorated. This system, known as the mucociliary clearance or escalator, forms a crucial barrier in the lungs against respiratory pathogens and external insults. + +Changes in the number or function of tracheal goblet cells can engender health complications. For example, goblet cell hyperplasia, or excessive growth of goblet cells, is a common feature of chronic inflammatory lung diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD). This condition results in mucus hypersecretion, airway blockage, and increased risk of respiratory tract infections. +" DOI:10.1016/S1357-2725(02)00083-3|DOI:10.1165/ajrcmb.25.5.f218|DOI:10.1164/ajrccm.154.6.8970383|DOI:10.2147/COPD.S38938|DOI:10.3109/01902148.2013.791733 +172 CL:1000348 CL_1000348 "Basal cells of epithelium of trachea are a vital cell population within the respiratory tract's lining, specifically in the trachea's epithelium. These cells are located at the base of the columnar epithelial cell layer and can be identified by their characteristic cuboidal shape, a large nucleus and few organelles, as well as scattered microvilli. The basal cells are not in direct contact with the lumen, which is covered by a layer of ciliated and non-ciliated columnar cells. Instead, the basal cells are connected to, and line, a thin basement membrane. + +The primary function of basal cells involves stem cell activity and epithelial tissue maintenance. Basal cells in the trachea play a crucial role in the regeneration and repair of the tracheal epithelium during damage or injury, acting as progenitor cells for ciliated and secretory cells. They serve as a reserve pool of cells, ready to proliferate and differentiate as needed for homeostatic tissue maintenance or in repair processes when the epithelium has been compromised, whether by injury or disease. + +These cells are also implicated in numerous disease pathways. Conditions like chronic obstructive pulmonary disease and lung cancer exhibit unusual behavior and quantities of tracheal basal cells, making these cells a focal point in respiratory disease research. In summary, basal cells in the tracheal epithelium have a multifaceted role in maintaining, repairing, and influencing tracheal health, playing a crucial role in the stability of the respiratory system. +" DOI:10.3389/falgy.2021.787128|DOI:10.1242/dmm.006031|DOI:10.1165/rcmb.2021-0150ED |DOI:10.1164/rccm.201408-1492PP +173 CL:1000343 CL_1000343 "Paneth cells of the epithelium of the small intestine, often referred to simply as Paneth cells, are a type of specialized secretory cell that forms an integral part of the intestinal crypts of Lieberkühn – gland-like invaginations lining the small intestine. Named after the Austrian physician Josef Paneth, who first identified them in the late 19th century, these cells are significant because of their substantial involvement in the mucosal immune system and intestinal stem cell maintenance. + +Functionally, Paneth cells play a key role in maintaining gut homeostasis and in the first line of antimicrobial defense, mainly through the secretion of a range of antimicrobial peptides and proteins. These include lysozymes, cryptdins, or alpha-defensins, which have potent activity against various gut pathogens including bacteria, fungi, and parasites. Furthermore, Paneth cells of the small intestine are also known to release secretory phospholipase A2, an enzyme active against gram-positive bacteria. Additionally, they secrete several growth factors like EGF, TGF-alpha, and Wnt3, which are crucial for stem cell support and the overall maintenance of intestinal mucosal integrity. + +The unique location of Paneth cells at the base of the crypts positions them in very close proximity to intestinal stem cells. This not only facilitates their role in stem cell maintenance but also involves them in epithelial regeneration and repair following injury. Dysfunctional Paneth cells have been associated with several gut disorders, like Crohn’s disease and necrotizing enterocolitis. + +" DOI:10.1146/annurev-physiol-030212-183744|DOI:10.1038/nrmicro2546|DOI:10.1038/nature09637|DOI:10.1007/s00018-002-8412-z|DOI:10.3389/fimmu.2020.00587 +174 CL:1000349 CL_1000349 "The basal cells of the epithelium of the bronchus are a vital component of the cellular linings found within the bronchial tubes of the respiratory system. They are typically nonciliated, cuboidal cells that are tightly attached to the basement membrane, thereby providing structural support for the epithelial tissues. + +The function of the basal cell of the bronchial epithelium is multifaceted, underscoring the importance of these cells for respiratory health. One of their primary roles involves regeneration and cellular turnover. They serve as local stem cells, being able to proliferate and differentiate into other cell types such as ciliated and secretory epithelial cells. This regenerative function of basal cells is required for maintaining the integrity of the bronchial epithelium and is especially critical after injury or during disease states when there is an increased need for new cells to repair damaged tissue or replace lost cells. + +In addition to these regenerative duties, basal cells of the bronchial epithelium play a crucial role in providing a defensive barrier against inhaled substances. They participate in the coordinated immune response directed against airborne pathogens, foreign particles, and toxins that enter the respiratory tract. Basal cells can respond to inflammation or irritation by altering their activities, which include proliferating, differentiating, or producing bioactive substances. Throughout all these responses, the basal cells help to maintain the homeostasis of the bronchial tubes, allowing for the efficient transport of air to and from the lungs. +" DOI:10.1038/labinvest.2015.114|DOI:10.1002/ar.1092380310|DOI:10.3389/falgy.2021.787128|DOI:10.1136/thx.2004.la0104 +175 CL:1000353 CL_1000353 "Microfold cells, also widely known as M cells, are a distinct type of epithelial cell found in the gut, including the small intestine, specifically within the Peyer’s patches, a component of the gut-associated lymphoid tissue (GALT). M cells play a crucial role in the immune response within the intestine environment. + +These cells are characterized by microfolds (short microvilli, which give them their name), a reduced, thin glycocalyx, and a deeply invaginated basolateral membrane next to immune cells such as B cells, T cells, and macrophages, and DCs. +These features allow the M cells to form the first point of contact between the gut lumen and the intestinal immune system. They are well-regulated gateways that capture and transport antigens, such as bacteria, viruses, and other foreign substances found in the lumen, to the underlying cells of the immune system. This specialized transport mechanism, called ‘transcytosis’, involves engulfment of these antigens from the apical side, transport across their cytoplasm, and release on the basolateral side of the cells, where immune responses can be initiated. + +Furthermore, M cells have complex interactions with members of the gut microbiota and other immune cells, making them essential for maintaining gut homeostasis. This cross-talk shapes the diversity and makeup of the gut microbiota, subsequently having a substantial impact on the host's health. In certain situations, pathogenic organisms can exploit the transcytosis mechanism to infiltrate the host's system, causing various infectious diseases. +The overarching significance of M cells in the small intestine lies in their role of surveillance and protection against a wide range of potentially harmful pathogens, while also facilitating beneficial interactions with commensal microbes. +" DOI:10.1111/j.1574-695X.2007.00359.x|DOI:10.3389/fimmu.2019.01499|DOI:10.1038/mi.2013.30|DOI:10.1093/jb/mvv121 +176 CL:1000432 CL_1000432 "Conjunctival epithelial cells are located in the outermost layer of the conjunctiva, the transparent mucous membrane that covers the front surface of the eye (sclera) and lines the inside of the eyelids. Depending on the location, the conjunctival epithelium varies from a stratified squamous non-keratinizing epithelium (close to the lid margin) to a stratified columnar epithelium (bulbar). It consists of between two and seven layers of epithelial cells, which are organized into three main types: basal, intermediate and superficial; amongst them are goblet cells, which produce the mucous layer of the tear film, + +The conjunctival cells play a vital role in preserving the health and functionality of the eye, contributing significantly to ocular defense mechanisms. They also participate in maintaining the ocular surface's physiological environment. Specifically, conjunctival epithelial cells serve as a physical barrier against environmental threats, such as dust, allergens, and microbes. They prevent foreign bodies from entering the eye, thanks to their tightly packed arrangement, which is integral to the eye's first line of defense. + +Apart from this physical protection, these conjunctival epithelial cells are also involved in immune defense. They secrete microbicidal and immunomodulatory peptides and cytokines and can recognize and respond to pathogens through their the Toll- and NOD-like receptor signaling pathways and modulate DC and lymphocyte function. + +Additionally, conjunctival goblet cells, assist in maintaining ocular surface moisture by secreting soluble mucins for tear film production, a thin fluid layer that keeps the cornea and conjunctiva moist. This tear film lubricates the eye, protects against infections, and ensures uninterrupted, clear vision. +" DOI:10.1016/j.celrep.2021.108715|https://www.sciencedirect.com/topics/neuroscience/conjunctiva-epithelium|DOI:10.1167/iovs.17-23623|DOI:10.1016/j.exer.2013.10.008|DOI:10.1111/imm.12716 +177 CL:1000448 CL_1000448 "Epithelial cells of sweat glands, also known as sudoriferous glandular cells, play a crucial role in the body's thermoregulation, waste excretion, and hydration balance. They form the main structure of the sweat glands, which are effectively long, coiled tubes located in the dermis. There are two types of sweat glands – eccrine glands, which typically open directly onto the skin surface (e.g. on palms and soles), and apocrine glands, which open onto associated hair follicles (e.g. in arm pits). + +Eccrine glands consist of a tube-shaped duct that ends in a coiled, secretory unit made up of three types of epithelial cells – dark, clear and myoepithelial. The dark cells contain basophilic granules to secrete sialomucin, while clear cells secrete glycogen-containing aqueous material; the myoepithelial cells contract in response to stimuli to assist with secretion. Apocrine glands have a similar structure, but their secretory component is larger. + +The primary function of the epithelial cells of these glands is to produce sweat, a bodily fluid made mostly of water, but also containing trace amounts of salts, glucose, urea, and other substances. This process begins with the secretion of a primary sweat fluid - an isotonic solution derived from the blood plasma - into the glandular lumen. Subsequently, as this primary sweat passes through the gland's duct, reabsorption of sodium ions occurs, leading to a hypotonic final sweat that is excreted onto the skin's surface. This sweat evaporates, removing heat from the body and thus, cooling it down. + +In addition, epithelial cells of sweat glands contribute to the body's immune defense system. As part of the innate skin barrier function, they secrete antimicrobial peptides and proteins, such as dermcidin, which can inhibit the growth of harmful microorganisms on the skin surface. They also aid in maintaining skin pH and contribute to fluid balance by regulating water resorption. Consequently, any dysfunction in these cells can lead to conditions like hyperhidrosis, anhidrosis, and certain skin infections. Thus, these epithelial cells of sweat glands play a multifaceted role in health and disease. +" https://doi.org/10.1038/s41419-019-1485-5|DOI:10.1080/23328940.2019.1632145|DOI:10.1111/exd.12773|https://www.ncbi.nlm.nih.gov/books/NBK513244/|https://www.ncbi.nlm.nih.gov/books/NBK482278/ +178 CL:1000449 CL_1000449 "Epithelial cells of the nephron form the epithelial lining of the nephron, the functional unit of the kidney that filters the blood to produce urine. Each kidney holds approximately one million nephrons, each of which is composed of several distinct parts, including the renal corpuscle, the proximal tubule, the loop of Henle, and the distal tubule. All sections are lined with highly specialized epithelial cells adapted to perform different functions within the sections of the nephron. + +The different epithelial cells of the nephron play crucial roles in the process of filtration, reabsorption, secretion, and excretion, essential tasks for the regulation of body fluid composition and volume. During filtration, the blood is forced through the walls of glomerular capillaries into the Bowman's capsule, where waste products, electrolytes, and water are separated from the blood cells and proteins. As the filtrate then passes through the nephron, epithelial cells of the tubular portion reabsorb useful substances such as glucose, amino acids, and electrolytes, along with most of the water back into the bloodstream. Waste products like urea and creatinine, as well as excess ions and water, remain in the tubule for elimination. + +In addition, epithelial cells of the nephron also play a vital part in maintaining the body's acid-base balance by actively secreting hydrogen ions into the urine while reabsorbing bicarbonate from the urine back into the blood. They are also involved in the regulation of blood pressure through the renin-angiotensin-aldosterone system and contribute to erythrocyte production by releasing the hormone erythropoietin in response to low oxygen levels in the blood. Abnormalities or damage in renal epithelial cells often result in impaired kidney function, leading to various renal diseases. +" DOI:10.1146/annurev-physiol-052521-121841|DOI:10.1007/978-94-011-2354-9_6|DOI:10.1016/B978-0-323-35775-3.00011-4|DOI:10.1007/s004670050586|DOI:10.1681/ASN.2012010029 +179 CL:1000495 CL_1000495 "Small intestine goblet cells are specialized epithelial cells found in the lining of the small intestine. They are scattered among other columnar cells in the small intestine lining and form a vital part of the intestinal villi—tiny, finger-like projections that boost the absorption of nutrients by increasing the surface area of the intestine. The name ‘goblet cell’ is derived from the cell's distinctive goblet shape, which features a broad apex and a narrow base. + +The primary function of the small intestine goblet cells is to secrete mucus, a thick and lubricating substance that plays a crucial role in the body's defense mechanisms. This mucus layer, formed through the aggregation of individual mucin glycoproteins produced by goblet cells and secreted from vesicles located near the apical membrane, provides a protective lining that safeguards the epithelial cells of the intestine from corrosive substances and pathogenic organisms. Moreover, the mucin layer helps in the smooth passage of food material along the digestive tract. + +Additionally, goblet cells in the small intestine contribute significantly to the maintenance of intestinal homeostasis. They actively engage in signal transduction pathways initiated by the native microflora and food antigens, modulating immune responses and preventing inflammation and autoimmunity. The mucus layer also functions as the habitat for beneficial bacteria, thereby facilitating a symbiotic relationship and promoting overall gut health. Any dysfunction or abnormality affecting these cells, such as depletion or hyperplasia, may potentially lead to severe gastrointestinal disorders such as inflammatory bowel disease. +" DOI:10.1111/imr.12182|DOI:10.1038/s41575-023-00761-8|DOI:10.1111/febs.15731|DOI:10.1038/mi.2015.32 +180 CL:1000510 CL_1000510 "Kidney glomerular epithelial cells are critical components of the kidney's filtration system; they include the epithelial cells of the glomerular capsule (podocytes and parietal epithelial cells) as well as the endothelial cells that line the glomerular capillaries. Collectively, these cells are integral to the renal glomerulus structure, which is a central part of the nephron, and is essential for filtering the blood and producing an initial filtrate that will serve as the starting point for the formation of urine. This filtration process is crucial for maintaining the body's fluid and electrolyte balance, as well as for eliminating waste products and excess substances from the bloodstream. + +The glomerular capillary endothelial cells line the inner surface of the glomerular capillaries and are in direct contact with the bloodstream. They have small fenestrations (pores) that allow small molecules such as water, electrolytes, and small solutes to pass through, but they prevent the passage of larger molecules like proteins. These endothelial cells are surrounded by the glomerular basement membrane, is a complex mesh of extracellular proteins, including proteoglycans, fibronectins, type IV collagen, and laminins. + +Parietal epithelial cells are arranged on the outer layer of Bowman's capsule, which surrounds the glomerular capillaries. They form a simple squamous epithelium, providing a structural lining for Bowman's capsule, and have recently come into focus as potential stem or progenitor cells for podocytes in glomerular regeneration. + +Podocytes maintain the glomerular filtration barrier and are crucial for ultrafiltration, a process that manipulates blood pressure to extract water, ions, and small molecules from the blood, while retaining larger molecules like proteins. They are differentiated epithelial cells that structurally comprise three parts: a cell body, major processes, and foot processes. The foot processes, or pedicels, wrap around the adjacent capillaries and leave slits between them, which act as a selective filter. Unique to podocytes is a complex slit diaphragm structure that bridges these filtration slits, preventing protein loss while allowing waste products to pass into the urinary system. This distinguishes them from most epithelial cells and reveals their specialized function in ultrafiltration. +Together, the different types of kidney glomerular epithelial cells work in a coordinated manner to filter and regulate the passage of substances from the blood into the renal tubules, ultimately forming the initial filtrate that will be processed into urine. + +" DOI:10.1159/000481633|DOI:10.1038/s41467-021-22331-9|DOI:10.1681/ASN.2020020220|DOI:10.1016/j.kint.2023.03.036 +181 CL:1000615 CL_1000615 "The kidney cortex tubule cell is a vital component of the regulatory and re-absorptive machinery in the kidneys. These specialized epithelial cells play an indispensable role in the regulation of salt, water, glucose homeostasis, and acid-base balance. They constitute the structure of the renal tubules of the nephron, part of which - the proximal tubule, the distal tubule and the connecting tubule, as well as the glomerulus – is located in the renal cortex, which is the outer part of the kidney. + +The epithelial cells in the kidney cortex tubules represent a heterogeneous population of cells, which are highly specialized, depending on their specific location. They are generally designed to execute transport processes across their apical and basolateral cell membranes, thereby enabling the reabsorption of necessary substances from the filtrate back into the blood, and the secretion of waste materials into the urine. +Proximal tubules compose the majority (∼66%) of kidney cells which have a multitude of transporters and exchangers in their cell membranes. To fuel the high-energy transport, the cells in the proximal tubule have one of the largest numbers of mitochondria in the body and are also very sensitive to injury. + +The cells in the distal convoluted tubule are responsible for regulating plasma sodium, calcium, potassium, and pH and are characterized by the presence of specific NaCl cotransporters and chloride/bicarbonate exchangers, as well as many other channels. Like the proximal tubule cells, they have a high mitochondria content, and they express large amounts of a ATP-dependent Na+/K+ pump. +Collectively, the epithelial cells in the kidney cortex tubules provide a crucial mechanism for the removal of endogenous organic cations, anions and drug elimination. Altered functionality of renal tubular cells can contribute to the onset and progression of chronic kidney diseases. + + +" DOI:10.1146/annurev-physiol-052521-121841|DOI:10.2147/IJNRD.S216673|DOI:10.1681/ASN.2019040415|DOI:10.3390/biomedicines9040426|DOI:10.1146/annurev-physiol-020911-153333 +182 CL:1000838 CL_1000838 "Kidney proximal convoluted tubule epithelial cells line the most voluminous part of the kidney's nephron, the proximal convoluted tubule, located in the cortex of the kidney. These cells are primarily involved in reabsorption and secretion processes, key functions that facilitate homeostasis within the body. + +Proximal convoluted tubule epithelial cells extensively function in the reabsorption process to a greater degree than their counterparts in the proximal straight tubule. Approximately two-thirds of filtrated sodium and water, nearly all nutrient sugars and amino acids, and a significant portion of bicarbonates pass through the proximal convoluted tubule, are effectively absorbed by the epithelial cells, and reenter the bodily circulation. By absorbing bicarbonates and secreting protons into the tubular fluid, proximal convoluted tubule epithelial cells also contribute to the pH regulation in the body . + +In addition to reabsorption, proximal convoluted tubule epithelial cells also play a critical role in the excretion of waste metabolites and xenobiotics. These cells possess a range of transporters that secrete metabolic end products and certain drugs, hence aiding in their elimination. This function underlines their importance for body detoxification. " DOI:10.1002/cphy.c110060|DOI:10.1681/ASN.2019040415|DOI:10.1146/annurev-physiol-052521-121841|DOI:10.1159/000092212 +183 CL:1000768 CL_1000768 "Kidney connecting tubule epithelial cells are found in collecting duct system of the kidney, specifically in at the interconnection segment between the nephron and the collecting ducts. The epithelial cells lining the connecting tubule are crucial for the journey of filtrate before it empties into urine-collecting ducts and therefore play a critical role in maintaining the body’s fluid and electrolyte balance. + +One of the principal functions of connecting tubule epithelial cells involves the selective reabsorption and secretion of various solutes. This reabsorption process includes critical regulatory electrolytes such as sodium ions (Na+), chloride ions (Cl-), and bicarbonate ions (HCO3-), thus playing a role in the regulation of the acid-base homeostasis. Their function also involves the secretion of potassium ions (K+) into the renal tubular fluid. + +The connecting tubule epithelial cells are primarily intercalated cells, which can be categorized into two types according to their specific functions: type A intercalated cells, which secrete acid, and the type B intercalated cells, which secrete base (bicarbonate) and reabsorb chloride. By regulating the concentrations of these ions, as well as reabsorption of water, connecting tubule epithelial cells contribute substantively to maintaining the body's electrolyte levels, pH balance, and overall homeostasis. + +In addition to intercalating cells, the collecting duct system also has principal cells, which are characterized by the expression of the water channel AQP2. AQP2-expressing cells have also been identified in connecting tubules, but there is some controversy whether these represent a unique cell type as there are some morphologic differences compared with principal cells. +" DOI:10.1002/cphy.c110052|DOI:10.1007/s00418-021-02033-5|DOI:10.23876/j.krcp.2017.36.4.305|DOI:10.1097/MNH.0b013e32820ac850|DOI:10.1681/ASN.2019040415 +184 CL:1000839 CL_1000839 "Kidney proximal straight tubule epithelial cells line the straight portion of the proximal tubule of the nephron, extending from the cortical medullary ray into the outer stripe of the outer medulla. They are characterized by a brush border of dense microvilli on their apical surface, enhancing the cell's surface area and aiding reabsorption, though reabsorption occurs more heavily in the proximal convoluted tubule preceding the straight portion of the tubule. + +The primary function of the kidney proximal straight tubule epithelial cells is to reabsorb the filtrate that the kidney produces, which includes glucose, sodium, and water. The reabsorption occurs through both passive and active transport methods. These cells exhibit enzyme-rich microvilli that also absorb small proteins and peptides. Consequently, they are involved in the regulation of plasma levels of various substances, including glucose, amino acids, and electrolytes, and maintain the body's pH homeostasis by secreting H+ ions into the urine and absorbing bicarbonate ions. + +These cells are also reported to be involved in drug metabolism. Many drugs are filtered from the blood by the kidneys and subsequently reabsorbed by the kidney proximal tubule epithelial cells back into the bloodstream. Furthermore, these cells play a significant role in the progression of kidney diseases. For example, in diabetic nephropathy and acute kidney injury, kidney proximal straight tubule epithelial cells can undergo cellular changes and result in malfunctions such as reduced reabsorption and increased excretion. " DOI:10.1002/cphy.c110061|DOI:10.1681/ASN.2019040415|DOI:10.2215/CJN.10391012|DOI:10.1146/annurev-physiol-052521-121841|DOI:10.1038/nrd4461 +185 CL:1001428 CL_1001428 "Bladder urothelial cells form the urothelium in the bladder - a specific type of epithelial tissue that constitutes the inner lining of the bladder and other parts of the urinary tract including the renal pelvis, ureters and urethra. These unique cells are specialized to withstand the highly variable and sometimes harsh conditions present in the urinary system. Their key function is maintaining the barrier integrity of the urinary tract even when exposed to high volumes of urine and its solutes, and they play a crucial role in protecting underlying tissues from damage and infection. + +The bladder urothelial cells exhibit a remarkable spectrum of phenotypic versatility and have an extraordinary capacity to stretch and retract based on the degree of bladder filling and emptying. In their relaxed state, these cells appear large and cuboidal, but upon stretching, they become thinner and exhibit a squamous cell-like appearance. This distinctive feature enables them to adjust to the changes in the urinary bladder volume while remaining impermeable to urinary solutes, thereby preventing a potential toxicity to the bladder wall and infiltration into the bloodstream. + +Apart from their barrier function, bladder urothelial cells also express a number of sensor molecules or respond to thermal, mechanical and chemical stimuli and can release signaling molecules, thereby playing a key role in sensory mechanisms that communicate vital information about the bladder's mechanical state to the nervous system. This communication helps regulate the micturition cycle and maintain urinary continence. Recent studies have also indicated that these cells may play a role in immune responses, highlighting their importance in bladder physiology. + +Altered proliferation and differentiation of bladder urothelial cells are implicated in various diseases and conditions such as bladder cancer, interstitial cystitis, and urinary tract infections. +" DOI:10.1080/03008880410015165|DOI:10.1038/s41585-020-0350-8|DOI:10.1038/nrurol.2016.13|DOI:10.1038/nrurol.2011.144|DOI:10.1038/s41579-020-0324-0 +186 CL:1001430 CL_1001430 "Urethra urothelial cells are highly specialized epithelial cells in the urethra, which is a tubelike structure that carries urine from the bladder to the external urethral orifice. Urothelial cells form the urothelium – a stratified, transitional epithelium lining the bladder, ureters, renal pelvis and urethra. These cells are highly adapted to their specific environment and maintain the crucial function of sustaining the urinary tract's core roles, primarily to transit and store urine without auto-corrosion or pathogen proliferation. + +Within the urethra urothelial cells are primarily found in proximal two-thirds of the urethra, while the distal third is lined by stratified squamous epithelial cells. The urothelial cells are renowned for their remarkable impermeability and ability to stretch and recoil during the various stages of urine filling and emptying. They form a tight barrier that prevents reabsorption of harmful byproducts and toxic substances present in the urine, guarding the deeper tissues and bloodstream against potential damage. This is largely attributed to specialized junctions, namely zonulae occludentes or tight junctions, in the umbrella cell layer (one of three layers of the urothelium) that seal the intercellular space between adjacent cells. Together with the urothelial plaque (an apical membrane plaque comprised of uroplakin proteins covering the umbrella cells at the luminal surface), the junctional complexes form a very effective permeability barrier that regulates the passage of water and ion from urine to the underlying tissue. + +A noteworthy feature of urothelial cells is their regulatory and sensory roles involving communication with the underlying layers about the filling and emptying status of the urinary tract. The cells also manage a fine balance between proliferation and differentiation, with the basal cells providing a ready pool of cells to replace the superficial layer when damaged. Their remarkable ability for regeneration and turnover, and their response to signals for repair underpins the durability and functionality of the urothelial tract. +" DOI:10.1152/physrev.00041.2019|DOI:10.1038/s41385-022-00565-0|DOI:10.1038/nrurol.2016.13|DOI:10.1152/physrev.00030.2012 +187 CL:1001516 CL_1001516 "Intestinal enteroendocrine cells are a highly specialized cell type found within the gastrointestinal epithelium. They account for approximately 1% of the intestinal epithelial cells in what is known as the largest endocrine organ in the human body. Intestinal enteroendocrine cells exhibit an exceptional diversity, both in terms of their secretory products and their distribution along the intestines, varying from the small intestine to the colon. + +The primary function of intestinal enteroendocrine cells is to maintain gut physiology and homeostasis. They are known for their hormone production and are the source of numerous bioactive molecules including somatostatin, serotonin, cholecystokinin, glucose-dependent insulinotropic peptide, motilin, neurotensin, and others. These hormones and neuropeptides act in autocrine, paracrine, or endocrine signaling, impacting various functions including intestinal motility, secretion, nutrient absorption, and gut barrier functions. + +Intestinal enteroendocrine cells also serve as the body's frontline of defense, playing an integral role in surveillance against lumen-occurring hazards including pathogen attack. Enteroendocrine cells are divided into ‘closed type’ and ‘open type’. Closed type cells are located close to the basal membrane and do not reach the lumen of the gut. In contrast, the apical side of the open-type intestinal enteroendocrine cells is directly exposed to luminal contents and thus can recognize bacterial metabolites and dietary nutrients. In response, these cells can modulate the immune system responses and thereby function as a key communicator between the gut microbiota and the host. +" DOI:10.1146/annurev-physiol-021115-105439|DOI:10.1111/j.1365-2613.2011.00767.x|DOI:10.1038/mi.2017.73|DOI:10.1038/s41574-019-0168-8|DOI:10.1016/j.coph.2013.09.008 +188 CL:1001589 CL_1001589 "Duodenum glandular cells are specialized secretory epithelial cells found in the duodenum, which is the first and shortest segment of the small intestine and consists of three structural layers – a mucosal membrane (mucosa), the submucosa with so-called Brunner’s glands, and a bilayer of smooth muscle (muscularis externa). Different glandular cells in the mucosa and submucosa secrete various enzymes and hormones crucial to digestion. + +A key function of the glandular cells in the duodenum involves the production of an alkaline mucus, which helps neutralize the acidic chyme, a semi-fluid mass of partly digested food, when it arrives from the stomach. They also secrete other enzymes responsible for breaking down molecules into simpler forms, thus making nutrients readily available for absorption. In addition, the glandular cells of the Brunner’s gland release secretin, a digestive hormone that regulates gastric acid secretion and pH levels in the duodenum, and cholecystokinin, which signals the gallbladder to release bile for fat digestion. + +Glandular cells in the duodenum possess a highly adaptive morphology that facilitates their crucial roles within harsh, dynamic digestive environments. The cellular structure equipped with microvilli on their apical surface increases their surface area, thereby enabling more efficient absorption of nutrients. Moreover, the cellular architecture allows a high secretion rate, crucial for managing variable conditions related to diet and digestion dynamics. Collectively, the different duodenum glandular cells have an essential role in maintaining optimal digestive function. +" DOI:10.1152/physiologyonline.2001.16.1.23|DOI:10.1007/s12325-021-01750-6|DOI:10.1016/j.jhep.2022.08.037|DOI:10.1016/j.beem.2004.07.002|https://www.sciencedirect.com/topics/medicine-and-dentistry/brunners-glands +189 CL:1001603 CL_1001603 "Lung macrophages refer to macrophage populations in the lungs, including the tissue-resident alveolar macrophages and interstitial macrophages, located in the air spaces and the connective tissue of the lung, respectively, and recruited macrophages. They are important in maintaining tissue homeostasis and immunity. + +The primary function of lung macrophages is to patrol and maintain the pulmonary system, where they serve as the first line of defense against airborne pathogens and inhaled particles. They perform phagocytosis of pathogens, particulate matter, dead cells, and other cellular debris from the lungs to maintain clear air passages and optimize gas exchange. They may also participate in tissue repair and the resolution of inflammation following injury. + +Lung macrophages also play a critical role in immune regulation. They help to initiate an immune response by secreting cytokines and other inflammatory mediators and by presenting antigens from the pathogens they have engulfed to induce T cell responses. However, if activated improperly, lung macrophages can contribute to inflammatory diseases of the lung such as chronic obstructive pulmonary disease (COPD) or asthma. +" DOI:10.1016/j.immuni.2022.08.010|DOI:10.3389/fimmu.2021.753940/full|DOI:10.1189/jlb.70.2.163|DOI:10.3390/cells10040897|DOI:10.1002/JLB.3RU0720-418R +190 CL:2000064 CL_2000064 "Ovarian surface epithelial (OSE) cells form the ovarian epithelium, a single layer of cells that covers the external surface of the ovaries, continuous with the peritoneal mesothelium. The epithelium varies morphologically from cuboidal, to simple flattened, and low pseudostratified columnar cells, depending on the cyclic changes in the underlying ovarian structure. + +The epithelial layer functions as a physical barrier that protects the ovarian stem cells and the follicular cells from mechanical stress and potential foreign pathogens, and they provide a supportive tissue microenvironment for the underlying cells of the ovaries. The OSE is separated from the ovarian stroma by a basement membrane, to which it is only loosely attached. + +OSE cells play a crucial role in ovarian physiology and pathology. They are involved in processes associated with ovarian follicular growth, maturation, ovulation and follicular atresia. Moreover, they have a prominent role in repairing the ovarian surface following the rupture of the follicle during ovulation, essentially playing a key part in the regenerative processes post-ovulation. Shedding and regeneration of OSE cells is a dynamic process that repeats throughout each reproductive cycle. + +OSE cells are also the primary origin of ovarian cancer, specifically, epithelial ovarian cancer which accounts for about 90% of all ovarian cancers. The constant rounds of rapid proliferation and repair following ovulation are thought to provide the opportunity for replication errors and hence contribute to neoplastic changes in the OSE. +" DOI:10.1210/edrv.22.2.0422|DOI:10.1073/pnas.0805012105|DOI:10.1677/JME-07-0149|DOI:10.3389/fendo.2022.886533 +191 CL:3000001 CL_3000001 "Hofbauer cells, also known as placental macrophages, are a population of specialized white blood cells that reside in the chorionic villus, the functional unit of the placenta. Named after Max Hofbauer, the scientist who first discovered them, Hofbauer cells are unique for their specific location and special role in fetal development and maternal-fetal interference. + +Hofbauer cells play a pivotal role in the development and maintenance of the placental villi, which are the primary structures that enable the exchange of nutrients, gases, and waste products between the mother and her fetus. Hofbauer cells contribute to the regulation of the structural composition of the placental villi by modulating the balance of pro-angiogenic and anti-angiogenic factors. For example, Hofbauer cells secrete vascular endothelium growth factor (VEGF), which has potent angiogenic growth properties by increasing vascular permeability and simulating migration of endothelial cells. + +The placental macrophages are also implicated in the immune tolerance associated with pregnancy, playing a vital role in preventing the mother's immune system from attacking the fetus. Hofbauer cells are present from 18 days gestation and for most of the gestation period they are the only detectable placental immune cell. Because they are located on the foetal side of the single-cellular syncytiotrophoblast layer that separates maternal and foetal blood, they are thought to play an integral role in setting the immune environment of the placenta. This function is achieved by promoting the production of anti-inflammatory cytokines and suppression of maternal T-cell activation. + +In addition, Hofbauer cells are involved in defense against pathogens invading the placenta. Given their role as a subtype of macrophages, they are capable of phagocytosis, a process where they ingest and destroy harmful bacteria or viruses, providing added protection for the developing fetus. Imbalances in Hofbauer cell homeostasis have been associated with placental pathologies involving infection, inflammation, and inadequate placental development. +" DOI:10.1159/000497416|DOI:10.3389/fimmu.2018.02628|DOI:10.3389/fimmu.2021.756035|https://www.sciencedirect.com/topics/immunology-and-microbiology/hofbauer-cell +192 CL:0002279 CL_0002279 "The type L enteroendocrine cell, also known as L-cell, is an integral part of the digestive system found in the intestine, primarily identified in the ileum and colon. These cells are distinguished among other cell types primarily because of their role in the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). Both peptides are essential for maintaining the body's energy homeostasis and the normal functioning of the gastrointestinal tract. + +In response to the ingestion of food, type L enteroendrocrine cells secrete GLP-1, a potent hormone that stimulates insulin secretion, lowers glucagon secretion, slows gastric emptying, enhances satiety, and has the potential to promote proliferation of type B pancreatic cells and improve their function. + +L-cells also secrete peptide YY (PYY), which plays a pivotal role in controlling appetite. Postprandially secreted into the bloodstream, PYY functions by decreasing appetite and food intake, thereby contributing to long-term energy balance. PYY can centralize the regulation of appetite via the hypothalamus." DOI:10.1016/j.cmet.2008.11.002|DOI:10.1042/CS20150154|DOI:10.1038/nrendo.2011.77|DOI:10.1111/j.1749-6632.2003.tb03176.x|DOI:10.1038/ncpendmet0318 +193 CL:0002306 CL_0002306 "An epithelial cell of the proximal tubule, commonly referred to as a proximal tubular epithelial cell, is a specialized brush border cell found lining the proximal tubule within the functional unit of the kidney, the nephron. These cells play a critical role in the resorption process in the kidney and are responsible for maintaining homeostasis, including blood filtration, electrolyte balance, and acid-base balance. Epithelial cells of the proximal tubule have a cuboidal shape and microvilli that increase surface area, facilitating effective reabsorption. + +The primary function of epithelial cells of the proximal tubule revolves around their ability to reabsorb approximately 60-70% of the glomerular filtrate, retaining essential substances such as sodium, glucose, amino acids, bicarbonate, and certain ions that are filtered out by the glomerulus. Additionally, these cells are also responsible for the secretion of organic acids, bases, and the hydrolysis of small proteins that are reabsorbed after filtration. + +Proximal tubule epithelial cells are highly susceptible to apoptosis, and damage to these cells by exposure to toxins, pathogens, or obstructive conditions may result in acute kidney injury." DOI:10.1007/s11033-020-05977-4|DOI:10.1002/cphy.c110061|DOI:10.2215/CJN.02440314|DOI:10.1073/pnas.0405179101|DOI:10.1038/ki.2011.120 +194 CL:4030006 CL_4030006 "Fallopian tube secretory epithelial cells are non-ciliated cells that form an integral part of the epithelial lining of the fallopian tubes, the delicate conduits leading from the ovaries to the uterus in the female reproductive system. These cells are specialized to produce and secrete various biochemical substances necessary for gamete transportation, fertilization, and early embryonic development. + +A key function of the different subtypes of secretory epithelial cells is to release various substances, including proteins, glycoproteins, and ions that create an environment conducive to the journey of the ova from the ovaries to the uterus. The secretions aid in multiple ways, such as nourishing and protecting the oocytes, facilitating their transportation, and preparing them for potential fertilization. Some of these secretions, like tubal fluid, provide the essential medium for the oocyte's transit and the sperm's locomotion, thereby playing a critical role in successful fertilization. + +In addition to their secretory function, fallopian tube secretory epithelial cells also contribute significantly to the formation of ciliated cells through differentiation, ensuring a functional fallopian epithelium and, subsequently, successful reproduction. They act as a frontline barrier against ascending infections by maintaining a robust immune environment. Recent studies also indicate their potential relevance in ovarian epithelial cancers, as the transformation of these cells might contribute to the development of this type of neoplasm. +" DOI:10.1016/j.devcel.2022.02.017|DOI:10.1016/S0143-4004(99)80008-3|DOI:10.1530/rep.0.1210339|DOI:10.1186/1471-2121-14-43|DOI:10.1016/j.ccr.2013.10.013 +195 CL:0019028 CL_0019028 "Midzonal region hepatocytes, also called mid-lobular hepatocytes, are a specific type of hepatocyte, the primary cell type within the liver. These cells are named for their location within the zonal structure of the liver and are found midway between the periportal and pericentral regions, forming the intermediate or middle zone (zone 2). Like all hepatocytes, midzonal region hepatocytes play vital roles in metabolic, detoxification, and synthetic activities key to maintaining the body's homeostasis. + +Midzonal region hepatocytes have specialized metabolic functions due to their location in the lobule's intermediate zone, which is also referred to as the midlobular or centrilobular region. The region-specific specialization of hepatocytes across the liver's lobule ensures efficient spatial distribution of tasks that contribute to liver function. Hence, the midzonal hepatocytes are exposed to intermediate concentrations of oxygen and nutrients, compared to the hepatocytes in the periportal or pericentral regions, which receive high or low blood flow respectively. + +Midzonal hepatocytes have unique regenerative capacity which is essential for the liver’s ability to restore function following injury and disease. They also have unique metabolic profiles, particularly concerning xenobiotic metabolism or drug metabolism, independent of the hepatocytes in the periportal and pericentral regions. + +The midzonal hepatocytes also play a significant role in the pathophysiology of liver diseases. Studies have highlighted that damage or cell death in the midzonal region hepatocytes is an early sign of liver-related conditions or exposure to harmful substances. Thus, midzonal hepatocytes serve as important markers for the detection of liver diseases due to their susceptibility to several forms of hepatic injury. The cell's functionality, therefore, is not just restricted to the maintenance of liver metabolic activities but also extends to the detection and early diagnosis of potential liver diseases. +" DOI:10.1038/s41575-019-0134-x|DOI:10.1038/s41575-020-0304-x|DOI:10.3389/fphys.2021.732929/full|DOI:10.1126/science.abb1625|DOI:10.1055/s-0041-1742279 +196 CL:0019026 CL_0019026 "Periportal region hepatocytes, also known as Zone 1 hepatocytes, are specialized epithelial cells located in the periportal region of the liver acinus, near the portal triad, which comprises the portal vein, hepatic artery, and bile duct. These cells form a major part of the liver's cellular architecture and play a pivotal role in detoxification, metabolism, and homeostasis processes in the human body. + +Periportal hepatocytes differ functionally from hepatocytes in the liver’s midzone (zone 2) and the pericentral zone 3. They are exposed to higher oxygen concentrations than hepatocytes in zones 2 and 3 because they are closer to the portal triads where oxygen-rich blood enters the liver. They therefore catalyze predominantly oxidative energy metabolism. + +Periportal hepatocytes are responsible for gluconeogenesis, the process by which glucose is synthesized from smaller precursor molecules like lactate, glycerol and glucogenic amino acids, to maintain blood glucose levels, particularly during fasting periods. Additionally, they carry out cholesterol synthesis, fatty acid oxidation, urea synthesis, and the conversion of ammonia to urea, aiding in the detoxification and excretory functions necessary to maintain homeostasis. Periportal hepatocytes are also associated with bile synthesis and secretion, given their proximity to the bile duct. Bile components facilitate the digestion and absorption of dietary lipids and the removal of waste products from the liver. + +Because of their location near the portal triad periportal hepatocytes are more resistant to ischemic injury than other hepatocytes but are more susceptible to toxic damage due to their higher exposure to drugs and toxins. +" DOI:10.1038/s41575-019-0134-x|DOI:10.1159/000469338|DOI:10.1093/jn/122.suppl_3.843|DOI:10.1159/000468779|DOI:10.1002/hep.1840010413 +197 CL:0019029 CL_0019029 "Centrilobular region hepatocytes, also referred to as perivenous or pericentral hepatocytes, are specialized cells that constitute the largest component of the liver. These cells are strategically arranged around the central vein of a liver lobule, forming the zone 3 region. This unique location is critically significant for their distinctive functional capabilities, making them different from periportal hepatocytes of zone 1 and midzonal hepatocytes of zone 2. + +One of the primary functions of centrilobular region hepatocytes is linked to the body’s metabolic detoxification processes. These cells are predominantly involved in xenobiotic biotransformation, assisting with the metabolism and excretion of foreign substances, such as drugs or harmful toxins. This role is facilitated by their ability to express high levels of Cytochrome P450 enzymes, which are pivotal in phase I detoxification reactions. Additionally, centrilobular region hepatocytes also play a crucial role in bile acid synthesis and the biotransformation of endogenous compounds such as steroids, fatty acids, and bilirubin. + +Being situated in zone 3, centrilobular hepatocytes are more susceptible to hypoxic injury than other hepatocytes due to the lower oxygen supply. Furthermore, due to their central role in detoxification, they are particularly prone to drug-induced hepatic damage. +" DOI:10.1038/s41575-019-0134-x|DOI:/10.3389/fphys.2021.732929/full|DOI:10.1042/bj3290017|DOI:10.1007/s10620-006-3174-3|DOI:10.1002/hep.510310201 +198 CL:0019031 CL_0019031 "The intestine goblet cell is a specialized cell type predominantly found within the epithelial lining of the intestinal tract, which includes both the small and large intestines. The name of these cells derives from their characteristic 'goblet' shape, which consists of a small basal nucleus and a large apical region filled with secretory granules. These cells are interspersed among other epithelial cells known as enterocytes, and together they make up a protective barrier against the external environment. + +The primary function of the intestine goblet cell is the synthesis and secretion of large quantities of mucin, which, when hydrated, forms a slippery and protective mucus barrier lining the gastrointestinal tract. This mucus layer is vitally important in maintaining the integrity of the epithelial barrier, protecting it from physical damage, chemical damage, and infection. It also facilitates the passage of digested food material through the intestines. In addition, the mucus serves as a habitat for commensal microbiota, which has a significant role in maintaining human health. + +The goblet cells also contribute to immune functionality: they secrete anti-microbial proteins, chemokines, and cytokines and contribute to immune homeostasis by conditioning the habitat for gut microbiota. Additionally, goblet cell-associated antigens aid in inducing oral tolerance, an active process of local and systemic immune unresponsiveness to orally ingested antigens such as food. Dysregulation in the number or function of goblet cells can contribute to pathological conditions, such as inflammatory bowel diseases and cystic fibrosis. " DOI:10.1111/imr.12182|DOI:10.1126/science.aaf7419|DOI:10.1038/s41575-023-00761-8|DOI:10.1111/febs.15731|DOI:10.1038/mi.2015.32 +199 CL:0019032 CL_0019032 "Intestinal tuft cells, also known as brush cells, are specialized epithelial cells found in the lining of the intestines. Their name stems from their distinctive morphology, characterized by a thick ‘tuft’, or brush-like, peak of long, tapering microvilli which project into the intestinal lumen. These cells impart a structural characteristic to the epithelium of the intestine, aiding in its function and interaction with the surrounding environment. Their abundance among the gastrointestinal tract varies but they are most commonly found in the small intestine. + +The primary function of intestinal tuft cells is to act as chemosensory sentinels, assisting in monitoring and responding to luminal factors. They possess a highly potent sensing mechanism, facilitated by a diverse set of receptors, such as the bitter taste receptor family and succinate receptor, and a complex signaling apparatus. These sensory capabilities enable them to initiate crucial immune responses to a variety of physiological stimuli, including parasites and bacteria. Evidence suggests that tuft cells perform a critical role in maintaining gut homeostasis and in initiating type 2 immunity against parasite infection. + +Moreover, intestinal tuft cells are also involved in regulating intestinal epithelial cell homeostasis and contributing to the regeneration and repair of epithelial tissue following damage. They produce several growth factors and cytokines which play essential roles in these processes. Despite being one of the least common cell types in the gut, the role of tuft cells in sensing, immunity and tissue regulation underlines their importance in maintaining gastrointestinal health. +" DOI:10.1371/journal.ppat.1010318|DOI:10.3389/fimmu.2022.822867|DOI:10.4049/jimmunol.1801069|DOI:10.1038/nature24489 +200 CL:0000019 CL_0000019 "Sperm cells, also known as spermatozoa or male gametes, are highly specialized cells that are pivotal for sexual reproduction in animals. Produced in the male reproductive organs, specifically the testes, sperm cells play an important role in the process of fertilization, where they fuse with a female gamete or egg cell (ovum) to form a zygote, which marks the beginning of a new organism. + +Sperm cells hold several unique traits that set them apart from other body cells. Structurally, a sperm cell possesses two main structures: the head, containing the nucleus carrying the paternal genetic information, and the flagellum, which generates energy and grants the sperm cell mobility + +The process of fertilization occurs when one sperm cell successfully penetrates the egg, delivering its genetic information, and ultimately leading to the formation of a new individual combining both paternal and maternal genetic materials. Notably, while hundreds of millions of sperm cells may be released during ejaculation, only one has the opportunity to successfully fertilize the egg, underscoring the highly competitive nature of this biological process." https://www.ncbi.nlm.nih.gov/books/NBK26914/|DOI:10.1152/physrev.00009.2020|DOI:10.1080/19420889.2015.1017156 +201 CL:0001035 CL_0001035 "Bone cells, also known as osteocytes, form the building blocks of the skeletal system. They represent the most common type of bone cell, making up approximately 95% of the total bone cell population in mature adult bone tissue. Osteocytes are a stellate shape with numerous long, slender dendritic processes. + +The formation of bone is a complex process involving the action of osteoclasts - cells that break down and reabsorb old bone, followed by osteoblasts that rebuild the bone. Osteocytes serve as coordinators for these two types of bone cells to ensure a balance in the bone remodeling process, contributing to maintaining both bone strength and mineral homeostasis. + +The primary functions of osteocytes involve the creation, maintenance, and repair of bone tissue. They ensure that bone remodeling is performed by forming a network within the bone and communicating with other cells to help them respond to mechanical strain and damage. + +A remarkable aspect of osteocytes is their ability to perceive mechanical forces, translating them into biochemical signals that regulate bone remodeling and adaptation. Defects in osteocyte function, aside from other bone cells, have been associated with several bone disorders such as osteoporosis, renal osteodystrophy, and skeletal manifestations of diabetes." DOI:10.1038/s41413-020-0099-y|DOI:10.1007/s00795-015-0099-y|DOI:10.1007/s11914-012-0105-4|DOI:10.1016/j.jot.2021.04.005 +202 CL:0002321 CL_0002321 "Embryonic cells in metazoans, which include all multicellular animals, are biological units in their earliest developmental stages from conception until the organism is fully formed. + +They are derived from a fertilized egg, which undergoes a series of cell divisions to produce a multicellular organism. During the early phases of embryonic development, these cells exhibit pluripotency, meaning they possess the potential to differentiate into a diverse array of specialized cell types that constitute different body tissues and structures. + +The balance between cell proliferation and differentiation in embryonic cells is crucial for successful development. When cells continue to divide without differentiating, overgrowth may occur leading to conditions such as teratomas (tumors of embryonic cells). Conversely, if cell differentiation proceeds at the expense of cell proliferation, developmental anomalies could occur regarding size or mass of the organism or its parts." DOI:10.1002/iub.1404|https://www.ncbi.nlm.nih.gov/books/NBK9906/|DOI:10.1093/molehr/gan048 +203 CL:0002371 CL_0002371 "Somatic cells represent the majority of the cell types in the human body. They are fundamental building blocks of organs, tissues, and other bodily structures, with every organ being composed of distinct subpopulations of these cells. + +The primary function of somatic cells is to maintain the function and survival of an organism. They carry significant information in the form of DNA, and through the process of mitosis, contribute to the repair and regeneration of body tissues. + +Further, some types of somatic cells work in a collaborative manner to form complex functional structures such as the skin and lining of the gut, demonstrating a higher level of organization. However, it's important to note that somatic cells are distinct from germ cells, which are responsible for sexual reproduction by forming sperm or eggs. Any alterations in the DNA of somatic cells, due to mutations, will not affect the offspring as they aren't involved in transmission of genetic information to the next generation. + +While most somatic cells contain two copies of each chromosome (diploid), a certain subset may possess a single set of chromosomes (haploid), specifically found in male ants, bees, and other hymenopterans. Hence, diversity is a defining characteristic of somatic cells, reflecting in their structures, roles, and genetic makeup." https://www.genome.gov/genetics-glossary/Somatic-Cells|https://www.ncbi.nlm.nih.gov/books/NBK557896/|DOI:10.1038/nrm3980 +204 CL:0009011 CL_0009011 "Transit amplifying cells (TACs) are an intermediate, undifferentiated population between stem cells and differentiated cells. They can be found in multiple regions such as the small intestine and the colon. TACs of the colon, are integral components of the colonic crypts and vital players in the maintenance of colonic tissue. + +These cells serve a critical function in the rapid and constant renewal of the epithelium lining the colon, with the whole epithelial surface renewed approximately every 5-7 days. They divide rapidly and progressively differentiate into mature columnar epithelium cells, including enterocytes, goblet cells, and enteroendocrine cells. The continued proliferation of transit amplifying cells is fundamental to maintain the balance in cell population while preventing tissue degeneration and maintaining a state of homeostasis. However, uncontrolled proliferation and compromised differentiation capacity can contribute to the development of colon cancers. " DOI:10.1016/j.cell.2014.02.057|DOI:10.1053/j.gastro.2018.08.016|https://www.sciencedirect.com/topics/immunology-and-microbiology/intestinal-stem-cell|DOI:10.3389/fbioe.2023.1189225|DOI:10.1172/jci.insight.150894 +205 CL:0009012 CL_0009012 "Transit amplifying cells (TACs) represent an intermediate population between stem cells and fully differentiated cells, and can be found in multiple regions such as the colon and the small intestine. The small intestine's efficiency in absorbing nutrients, its protective barrier function, and its innate cellular renewal every few days is largely dependent on the role played by these TACs. + +TACs of the small intestine are primarily present in the crypt-villus structure of the intestine, more specifically in the crypt region. They originate from Lgr5+ intestinal stem cells that reside at the base of the crypts. Following their derivation from stem cells, TACs undergo up to six rounds of rapid division over a 48-72 hour period, effectively amplifying the cell population, hence their name. During this process, they gradually migrate upward along the walls of the crypt from where they differentiate into diverse mature cell types such as enterocytes, goblet cells, and Paneth cells. + +TACs serve as an important element in the homeostasis and regeneration of the intestinal epithelium, amplifying the pool of cells available for differentiation. They also minimize genetic errors during DNA replication by serving as a 'buffer zone' between the long-lived stem cells and the terminal differentiated cells of the gut lining, thus reducing the potential for propagation of mutation-causing defects. Lastly, TACs play an essential part in gastrointestinal tissue repair following injury or inflammation. Their rapid proliferation and subsequent differentiation abilities often help expedite the wound healing process in the intestinal epithelium." DOI:10.1016/j.cell.2014.02.057|DOI:10.1101/gad.1674008|DOI:10.1007/s11894-010-0130-3 +206 CL:0011020 CL_0011020 "Neural progenitor cells (NPCs) are a special type of cell found within the nervous system. NPCs primarily arise from the neural plate, which is a thickened area of the embryonic ectoderm, the outermost layer of an embryo. + +NPCs are characterized by their ability to self-renew through mitotic cell division in a process known as proliferation and possess the potential to differentiate into specific types of neural cells such as neurons, astrocytes, and oligodendrocytes. The type and number of cells that an NPC can produce depend on temporal and spatial signals in the nervous system microenvironment. + +Their primary function is to contribute to neurogenesis, the process of forming new neurons, primarily during embryonic and fetal development, but also continuing into adulthood in specific regions of mammalian brain. NPCs also have the potential to repair damaged or diseased nervous tissue because of their capacity to generate almost all cell types found in the nervous system. As such, they have been studied in the context of neurodegenerative diseases, spinal cord injuries, and brain injuries. " DOI:10.1101/cshperspect.a015719|DOI:10.3389/fnana.2018.00104|DOI:10.3389/fnins.2022.970350 +207 CL:1000330 CL_1000330 "Serous cells are specialized epithelial cells and can be found lining the trachea and brochus. They are among the major components of the respiratory epithelium. + +These cells are known for their production and release of serous secretions, which form a key component of airway mucus. These secretions primarily comprise of water, proteins, and enzymes, such as lysozyme and peroxidases. Their main purposes are to provide hydration and lubrication to the airway tissue and to act as a defense mechanism against pathogens. While the lysozyme and peroxidases contribute to the destruction of bacteria, the water in the secretions helps to liquefy the mucus, facilitating the effective functioning of the ciliated cells that propel the mucus up the trachea. + +The coordinated action between serous cells and other cell types in the tracheal epithelium proves essential for maintaining a healthy respiratory tract. Dysfunction or damage of these cells can lead to various respiratory tract disorders, such as cystic fibrosis and asthma. " DOI:10.1002/dvdy.24250|DOI:10.1016/B978-012330215-1/50029-6|DOI:10.1074/jbc.M208826200|DOI:10.1016/S0034-5687(01)00214- +208 CL:1000331 CL_1000331 "Serous cells of the epithelium of the bronchus, also termed bronchial serous cells, are predominantly found within the seromucous glands located in the bronchial submucosa. Serous cells can also be found in the trachea and are characterized by small, sparse, electron-dense granules. + +Serous cells are specialized cells responsible for the production and secretion of serous fluid. Serous fluid, mainly composed of water, proteins, and various types of salts, provides many benefits: it helps moisturize the airways, keep the bronchial tube walls moist, and safeguard the bronchial tubes against various foreign particles and infectious agents such as bacteria and viruses. Moreover, the fluid released by these cells assists in the lubrication and reduced friction in the bronchi, allowing for smoother airflow. +" https://www.ncbi.nlm.nih.gov/books/NBK534789/|DOI:10.1152/physrev.00039.2014|https://www.sciencedirect.com/topics/neuroscience/secretory-cell +209 CL:0019001 CL_0019001 "Serous cells of the tracheobronchial are found on the surface epithelium, submucosal glands, or both, depending on species. They appear in tubulo-acinar arrangements in submucosal glands. + +Tracheobronchial serous cells play a vital role in maintaining respiratory health by secreting serous fluid, which is rich in enzymes, ions, and antimicrobial proteins. This serous fluid is essential in clearing out debris, trapping and neutralizing inhaled pathogens and particulate matters, thereby helping in preventing infections. Their secretory products also include water and electrolytes that, combined with mucus (from mucous cells), maintain proper humidity within the airway and lubricate its surfaces, facilitating unhindered airflow. Dysfunction of these cells may lead to diseases such as cystic fibrosis. + +" DOI:10.1146/annurev.ph.52.030190.000525|DOI:10.1152/ajplung.00068.2019|DOI:10.1113/jphysiol.2003.052779|DOI:10.1016/j.resp.2007.06.017 +210 CL:1000271 CL_1000271 "A lung ciliated cell, also known as a ciliated bronchial epithelial cell, is a specialized type of epithelial cell located in the lining of the bronchi and bronchioles (airways) of the lungs. These cells house several hundreds of slender, hair-like structures known as cilia that extend out from the cell surface into the airway lumen. + +The main function of the lung ciliated cell is to facilitate the transportation of mucus, which acts as a physical barrier protecting the lungs from inhaled particulates, pathogens, and toxins, towards the throat, thereby contributing to the lung's innate defense mechanism. + +Furthermore, lung ciliated cells posses receptors that can detect the presence of disease-causing microbes, resulting in the release of chemokines and cytokines to attract and activate the immune cells. In summary, lung ciliated cells perform multifaceted roles essential for maintaining the health and function of the lungs, providing both a first-line physical defence system and a biological immune response to potential threats." https://www.sciencedirect.com/topics/immunology-and-microbiology/respiratory-epithelium|DOI:10.1152/ajplung.00283.2020|DOI:10.3389/fimmu.2020.00761 +211 CL:1000272 CL_1000272 "Lung secretory cells or club cells (formerly known as Clara cells) predominantly reside within the bronchioles of the mammalian lung. They have a characteristic apical dome shape and are filled with secretory granules. Lung secretory cells are non-ciliated, setting them apart from the neighboring ciliated cells. + +One of the primary roles of lung secretory cells is the production and secretion of a variety of proteins. Among these is club cell secretory protein (CCSP), which functions as a defensive mechanism, exhibiting anti-inflammatory and immunomodulatory properties. In addition to CCSP, these cells also secrete surfactant proteins A and D. These surfactants reduce surface tension in the alveoli, preventing their collapse and helping to maintain efficient gas exchange. Furthermore, lung secretory cells also detoxify harmful substances inhaled into the lungs, protecting the respiratory system from potential damage. +" DOI:10.1242/dev.143784|https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/club-cell|DOI:10.1146/annurev-med-042921-123443|DOI:10.1210/en.2008-0638|DOI:10.1164/rccm.201710-2107OC +212 CL:1000600 CL_1000600 "A lower urinary tract cell is a type of epithelial cell found within the proximal region of the human urinary system. The lower urinary tract comprises two primary components: the bladder, which stores the urine, and the urethra, through which the urine is expelled from the body. The cells that constitute these regions are specialized with unique morphologies and functions that aid in the execution of their roles in urine storage and excretion. + +One of the main types of lower urinary tract cells constitute the lining of the urinary bladder, known as urothelial or transitional cells. These cells exhibit the unique capacity to expand and retract with varying urine volumes.They also create a barrier against urine solute diffusion and can withstand osmotic changes and potentially harmful substances present in urine. This functional adaptability is crucial for preserving the integrity of the urinary tract and, consequently, the body's homeostatic balance. + +The urethra, on the other hand, is lined by a variety of cells including stratified and pseudostratified columnar epithelial cells, and near the external urethral orifice, stratified squamous epithelial cells. These cells fulfill a crucial role in maintaining the regular function of the urethra, protecting it against potential pathogens while ensuring the efficient expulsion of urine. " DOI:10.1128/microbiolspec.uti-0016-2012|DOI:10.1007/978-1-62703-125-7_23|DOI:10.1152/physrev.00030.2012 +213 CL:1001319 CL_1001319 "Bladder cells, also known as urothelial or transitional cells, form an integral part of the urinary bladder, which stores urine until it is expelled from the body. They are characterized by their unique capability to transform in response to the stretching and contraction of the bladder. In a relaxed state, the bladder cells appear thick and cuboidal. However, as the bladder fills and expands, these cells stretch, becoming thin and squamous, thereby increasing the bladder's storage capacity without compromising the integrity of the barrier. Moreover, the cells of the bladder are coated with a layer of glycoproteins known as uroplakins, which is impermeable and prevents urine from seeping back into the body's system. + +Bladder cells also play a vital role in protecting the body from urinary tract infections. The superficial layer of the urothelium serves as a physical impediment to pathogens, preventing them from reaching and damaging the deeper layers of the bladder wall. Any pathogens that manage to adhere to the superficial urothelial cells are often shed during urination, providing an efficient mechanism of cleansing the urinary tract. " https://www.ncbi.nlm.nih.gov/books/NBK482181/|DOI:10.1146/annurev-immunol-101220032117|https://www.ncbi.nlm.nih.gov/books/NBK540963/ +214 CL:2000021 CL_2000021 "Sebaceous gland cells, also known as sebocytes, are small, oil-producing glands present in the skin of mammals. These specialized cells are predominantly located in the dermis, particularly on the face, scalp, and upper body. + +The primary function of sebaceous gland cells is the production and secretion of sebum, a complex mixture of lipids including triglycerides, wax esters, squalene, and metabolites of fat-soluble vitamins (such as vitamin E), as well as free fatty acids. The production process involves a unique form of programmed cell death called holocrine secretion. In this process, as sebaceous gland cells mature, they progressively accumulate lipid droplets, before ultimately disintegrating and releasing their lipid-rich contents into the gland's ductal system. + +The sebum generated by these cells serves multiple purposes. It acts as a waterproofing agent, preventing excessive wetting or drying of the skin and averaging skin's water-holding capacity. Sebum also has antimicrobial properties, providing a natural defense barrier against certain bacterial and fungal species. Additionally, it contributes to the skin’s suppleness and prevents it from becoming brittle. An overproduction or imbalance of sebaceous gland cells can lead to common skin disorders, such as acne, seborrhea, or rosacea, illustrating their importance in skin health." DOI:10.4161/derm.1.2.8472|DOI:10.1016/j.jid.2016.10.017|https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/sebum|DOI:10.1080/19381980.2017.1375636|https://doi.org/10.2147/CLEP.S323744 +215 CL:0000015 CL_0000015 "Male germ cells are specialized cells that give rise to the male gametes and are therefore crucial for sexual reproduction in males. Through a complex process called spermatogenesis in the testes male germ cells undergo several stages of development, each with distinctive morphological and physiological characteristics, eventually differentiating into mature spermatozoa (sperm). + +Male germ cells are responsible for transferring genetic material from male to offspring as part of sexual reproduction. In the initial stage of their life cycle, they exist as spermatogonial stem cells, which multiply by mitotic division to self-renew and to produce daughter cells. The daughter cells then undergo meiotic division, a process that reduces the number of chromosomes in each cell by half, from diploid to haploid – the formation of spermatids. This is critical for maintaining genetic stability from generation to generation, as it ensures that when an egg and sperm cell unite during fertilization, the resulting offspring will have the correct number of chromosomes. The final phase of spermatogenesis is called spermiogenesis, during which spermatozoa - mature and motile sperm cells – are produced from round spermatids. + +The matured male germ cells or sperm cells are highly specialized, having a streamlined shape designed for efficient movement towards the female egg. A sperm cell is divided into three main parts, namely the head, midpiece, and tail. The head contains the genetic material, the midpiece contains mitochondria that provide energy, and the tail, termed as the flagellum, propels the sperm cell forward. Each of these parts play significant roles in fertilization. +" DOI:10.1242/dev.202046|DOI:10.1016/S1534-5807(02)00173-9|DOI:10.1016/S0092-8674(00)81834-6|https://www.ncbi.nlm.nih.gov/books/NBK553142/ +216 CL:0000300 CL_0000300 "Gametes are reproductive cells essential for sexual reproduction in eukaryotic organisms, including humans, animals, and many plants. These cells are haploid, containing half the genome or only one set of chromosomes, which is a contrast to the diploid state (two sets of chromosomes) found in most cells in a multicellular organism. This reduction in genetic material is crucial since it allows for the re-establishment of the diploid number of chromosomes when two gametes merge to form a diploid zygote during fertilization. + +There are two major types of gametes in animals: sperm cells in males and egg (or ova) in females. These gametes contribute equally to the genetic makeup of the offspring but are morphologically and functionally distinct. Sperm cells (or spermatozoa) are characterized by their motility, small size, and large quantities; they are produced continuously in vast numbers through a process called spermatogenesis in the male gonads or testes. Female gametes are much larger, fewer in numbers, and are not motile; they undergo a development process known as oogenesis, which takes place within the ovaries. The egg also contributes most of the cytoplasm and organelles (including mitochondria) to the zygote that are required for initial cell division stages after fertilization. + +Gametes have a primary role in sexual reproduction and genetic variation, which aids in evolution. The formation of gametes involves a special type of cell division called meiosis that introduces genetic diversity via the process of recombination and independent assortment. Following the fusion of male and female gametes, the combination of paternal and maternal genetic material in the zygote allows for genetic recombination, which is a fundamental source of genetic variation and, thus, evolution. Therefore, gametes not only are critical to the inception of new individuals but also contribute to species survival and evolution. +" DOI:10.3389/fcell.2022.1040708|DOI:10.1038/s41586-020-2347-0|https://www.ncbi.nlm.nih.gov/books/NBK553142/|https://www.ncbi.nlm.nih.gov/books/NBK10008/ +217 CL:0000408 CL_0000408 "The male gamete, also known as a sperm cell, is a highly specialized cell type critical to sexual reproduction. Sperm are produced during a process called spermatogenesis within the male reproductive organ, specifically the testes. They are haploid cells, carrying the genetic material from the male parent, and fuse with the ovum, the female gamete, to form a diploid zygote during fertilization, thereby initiating gestation and the development of a new organism. + +The male gamete is distinguished by its morphology, notably its elongated shape which is geared towards locomotion. One of the primary characteristics of a male gamete is its flagellum, or tail, which propels the cell towards the female gamete. It additionally contains an elongated head region housing the nucleus, where the genetic material is stored. The anterior section of the head, the acrosome, releases enzymes essential for penetrating the protective layers of the ovum during the fertilization process. + +The function of male gametes does not cease upon fertilization. In addition to delivering the paternal set of chromosomes, fusion of the sperm cell with the ovum causes an increase in cytosolic Ca2+ which then activates the female egg cell to undergo the so-called cortical reaction during which the egg’s zona pellucida is changed so fusion with additional sperm is prevented. The Ca2+ signal also initiates the development of the zygote and eventual formation of an embryo. Male gametes also contribute towards forming the placenta, which supplies nutrients and removes waste products during gestation. +" DOI:10.1242/dev.202046|https://www.ncbi.nlm.nih.gov/books/NBK553142/|DOI:10.1016/j.semcdb.2016.04.009|https://www.ncbi.nlm.nih.gov/books/NBK26843/ +218 "The kidney collecting duct intercalated cell, otherwise referred to simply as the intercalated cell, is a specialized epithelial cell type primarily found in the kidney's collecting duct system. It is among the main cells that line this final component of the nephron, crucial in the physiological system that maintains acid-base homeostasis. This unique cell type comes in mainly three subtypes as per the localization of their proton pumps: type A, type B, and non-A, non-B cells. Each subtype plays different roles in regulating acid-base balance and electrolyte homeostasis in the body under varying physiological conditions. + +Type A intercalated cells reabsorb bicarbonate and secrete protons into urine, leading to the production of acidic urine. These cells are typically prevalent on the renal cortex and function particularly in states of metabolic acidosis or potassium depletion. On the other hand, type B intercalated cells secrete bicarbonate and reabsorb protons; thus, they are crucial in alkaline urine production and potassium conservation. These cells are essential to counter metabolic alkalosis or situations of potassium surplus. The non-A, non-B cells have the characteristic features of both type A and B cells, but play a prominent role under conditions of chronically elevated aldosterone and angiotensin II levels. + +Through their differentiated roles, intercalated cells also facilitate the reabsorption of sodium and chloride ions, and water to maintain osmolarity. These cells' activity is finely regulated by hormonal signals like aldosterone, angiotensin II, vasopressin, and the parathyroid hormone. Intercalated cell activity can undergo a significant transformation under pathological conditions, and their dysregulation is associated with diseases such as distal renal tubular acidosis, hypertension, and chronic kidney disease. " DOI:10.2215/CJN.08880914|DOI:10.1152/physrev.00011.2019|DOI:10.1152/physiol.00008.2011|DOI:10.1007/978-3-211-99390-3_106|DOI:10.3390/diseases2020071 +219 CL:0002223 CL_0002223 "The anterior lens cells, also known as lens epithelial cells, are an integral part of the eye's structure and play a critical role in the organ's physiological functioning. They are situated in the anterior portion of the lens, precisely in the lens capsule, and stretch over the lens' frontal surface. + +The primary function of anterior lens cells is to facilitate eye accommodation by controlling the shape and thickness of the eye lens. + +The cells are involved in continuous proliferation, migration, and differentiation into lens fiber cells, helping to maintain lens growth and transparency. Anterior lens cells have a prolonged life span and reveal an extraordinary ability to function indefinitely, a characteristic that is critical for maintaining lens transparency. Damage or disturbance to the anterior lens cells can give rise to lens opacity, eventually leading to cataracts, which is a common cause of vision loss. +" DOI:10.1111/aos.14600|DOI:10.1016/j.biocel.2007.10.034|DOI:10.1155/2021/9951032 +220 CL:0000083 CL_0000083 "Epithelial cells of the pancreas, also known as pancreatic epithelial cells, are vital components of the pancreas, a glandular organ structured with glandular epithelium that plays a critical role in the digestive system. These cells are organized into two types of tissue in the pancreas: exocrine tissue and endocrine tissue. + +The exocrine tissue, which makes up majority of the pancreas, is responsible for the secretion of pancreatic enzymes which aid in digestion. This type of tissue consists of acinar cells that synthesize and secrete digestive enzymes, and ductal cells that direct these enzymes into the duodenum, the first section of the small intestine. These enzymes break down food in the small intestine, allowing the body to absorb nutrients. Malfunction of exocrine cells can lead to diseases, such as pancreatitis, leading to poor digestion and malnourishment. + +The endocrine tissue of the pancreas, structured into small islands called the Islets of Langerhans, consists of four types of cells: alpha cells, beta cells, delta cells, and gamma cells. These cells produce and secrete crucial hormones. Alpha cells produce glucagon, beta cells produce insulin, delta cells produce somatostatin, and gamma cells produce pancreatic polypeptide. These hormones control the level of sugar in the bloodstream and regulate the metabolism of glucose and fat. Beta cells, in particular, play a crucial role in preventing hyperglycemia. Diseases such as diabetes result from the malfunctioning of these endocrine cells, specifically the beta cells when they fail to produce enough insulin. Thus, pancreatic epithelial cells have an immense role in both digestion and hormonal secretion, contributing significantly to overall body homeostasis." DOI:10.1016/j.semcdb.2018.08.012|DOI:10.3389/fphys.2022.807632|DOI:10.1172/JCI57131|DOI:10.1002/wdev.44|DOI:10.1002/9781119188421 +221 CL:0002364 CL_0002364 "Cortical thymic epithelial cells (cTECs) are a vital cell type located in the thymus, a lymphoid organ that plays a key role in the development of T cells, which are essential for the adaptive immune system. cTECs also have a role in forming barriers and lining surfaces. In the thymus, their presence contributes to the distinctive architecture of both the cortex and medulla. + +cTECs also play a significant part in the selection and development of T cells. During T cell maturation, these cells express both self and non-self proteins via the major histocompatibility complex (MHC) to immature T cells. cTECs then stimulate the T cells that can recognize such proteins, an important event known as positive selection. This process aids in the creation of a diverse T cell receptor (TCR) repertoire that can react to a wide range of antigens, therefore ensuring effective immunity. + +Apart from aiding in T cells' positive selection, cTECs also contribute to eliminating self-reactive T cells, a role essential in preventing autoimmune diseases. These cells induce an apoptosis-driven process known as ""negative selection"" which eliminates T cells that are too highly reactive to self-antigens. + +" DOI:10.1038/nri3667|DOI:10.1016/bs.ai.2014.09.003|DOI:10.1111/sji.13094 +222 CL:0002365 CL_0002365 "Medullary thymic epithelial cells (mTECs) are distinct cells situated in the thymic medulla, a vital organ where T cells mature. mTECs are recognized by their unique appearance, characterized by large, plump cells with abundant cytoplasm and irregularly shaped nuclei. They inhabit a microenvironment closely interacting with various thymic cell types, including conventional dendritic cells and thymocytes. + +The primary function of mTECs revolves around negative selection of developing T cells, thus preventing autoimmune responses. mTECs allow developing T cells to recognize and be responsive to foreign antigens while remaining tolerant to the body's own tissues. They achieve this through a process called promiscuous gene expression where they express and display a vast array of self-antigens. This process is regulated by a transcriptional regulator called autoimmune regulator (Aire), which contributes to immunological self-tolerance. + +mTECs themselves have a self-renewing ability and sustain the continuous export of mature T cells. They also express a number of genes that encode for chemokines and other signaling molecules which draw in and retain developing T cells for the process of negative selection. The three-dimensional network formed by these cells provides a physical platform for such selection. Together, mTECs hold a critical place in the maintenance of immune homeostasis, demonstrating the conceptual links that exist between population of stromal cells, thymocytes development, tissue-restricted antigen expression, and negative selection. +" DOI:10.1007/s11427-013-4482-4|DOI:10.4049/jimmunol.2100692|DOI:10.7554/eLife.60188 +223 CL:0002563 CL_0002563 "Intestinal epithelial cells (IECs) are a diverse group lining the entire gastrointestinal tract from mouth to anus. + +IECs play a critical role in gut immunity. They defend against pathogens while supporting beneficial bacteria through antigen sampling, antimicrobial peptide secretion, and mucus production. They also modulate immune responses, interact with other gut cells, and facilitate immune cell movement. + +Additionally, IECs can sense changes in the gut environment through receptors like taste and toll-like receptors. When they detect changes, they signal local and distant cells and organs to adapt. This crosstalk impacts both gut and systemic functions. In summary, IECs are central to maintaining gut integrity and overall health." DOI:10.4161/gmic.19320|DOI:10.1111/imm.13117|DOI:10.3389/fimmu.2023.1171680 +224 CL:0002254 CL_0002254 "Epithelial cells of the small intestine, also known as enterocytes, comprise the majority of cells in the small intestine and hold a crucial role in the body's digestive system. They are columnar in shape, incorporating tight junctions at their borders to facilitate nutrient absorption while maintaining an effective barrier between the gut lumen and the body's internal environment. The surface of these epithelial cells presents small finger-like protrusions called microvilli, forming an integral part of the brush border, which is vital for increasing the surface area to maximize nutrient absorption. + +Each epithelial cell of the small intestine has a function tied intimately to its specialized structure. As a primary agent of absorption, it is responsible for the uptake and internalization of dietary nutrients such as carbohydrates, proteins, and fats, along with water and electrolytes, thus contributing significantly to the body’s nutrition. The microvilli on the cell surface express several enzymes that facilitate the digestion of nutrients prior to absorption, a process called luminal digestion. + +The epithelial cells of the small intestine also play an essential role in preserving the intestinal mucosal barrier and protecting the body against invading pathogens. These cells secret protective mucus and generate antimicrobial peptides, fortifying the body's innate immune response. In conclusion, the epithelial cells of the small intestine fulfill multifaceted tasks that are central to both digestion and immunity, underscoring their importance in maintaining overall health." DOI:10.1038/emm.2017.20|DOI:10.1007/s00441-010-1082-5 +225 CL:0002253 CL_0002253 "Epithelial cells of the large intestine, also known as colonic epithelial cells, are a specialized type of epithelial cell located in the lining of the large intestine. Epithelial cells form a contiguous cellular layer, the epithelium, which serves as a critical barrier between the innermost asset of the large intestine - the lumen, and the rest of the body. Structurally speaking, these cells are uniquely oriented with an ""apical"" (top) side facing the lumen and a ""basal"" (bottom) side interacting with underlying cells and connective tissue. + +The large intestinal epithelial cells are generally categorized into four major cell types: absorptive cells, goblet cells, enteroendocrine cells, and Paneth cells, each having a distinct role and function. + +Absorptive cells, or enterocytes, are the most common cell type in the colonic epithelium, responsible for water and electrolyte absorption, contributing to stool formation. Goblet cells, recognized by their cup-like shape, produce mucus, lubricating stool passage and acting as a protective barrier against pathogens. Enteroendocrine cells, forming the largest endocrine system in the human body, secrete hormones like serotonin, somatostatin, and peptide YY, regulating gut functions. Paneth cells, although more common in the small intestine, are present in the large intestine to some extent, contributing to innate immunity by releasing antimicrobial peptides, defending against microorganisms. Therefore, large intestine epithelial cells, appearing as a single layer, display diverse functions, ensuring overall health and homeostasis." DOI:10.1038/emm.2017.20|DOI:10.1016/j.it.2018.04.002|DOI:10.1093/ibd/izz217 +226 CL:0002293 CL_0002293 "Epithelial cells in the thymus, often referred to as thymic epithelial cells (TECs), are critical components of the thymus. Using complex molecular signaling pathways, these TECs help mediate the differentiation, maturation, and selection of thymocytes, thereby shaping the T-cell repertoire and maintaining immune function. Notably, two primary subtypes of TECs are known: cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells (mTECs), each with distinct functionalities. + +cTECs are primarily responsible for the initial stages of T-cell development. These cells play a critical role in promoting the expression of genes associated with the recognition of self-peptides, which is vital for enabling the selection of T-cells. On the other hand, mTECs are involved in the later stages of T-cell maturation, expressing tissue-restricted antigens (TRAs) for the purpose of facilitating the selection of T-cells that can distinguish between self and non-self, a mechanism crucial for preventing autoimmune responses. + +Moreover, TECs are known to secrete various cytokines like interleukins and chemokines, which are vital in the recruitment of thymocytes to the thymus, their movement within the thymus, and their development into mature T-cells. Additionally, TECs help establish a unique microenvironment within the thymus, which is essential for the homeostatic control of the T-cells. Over time, the function of TECs declines, which could potentially contribute to immune system aging. Given their crucial role in immune function, understanding the biology of thymic epithelial cells can provide significant insights into immune health, autoimmune diseases, and therapies targeting the immune system." DOI:10.1146/annurev-immunol-051116-052320|DOI:10.1186/s13148-021-01197-0|DOI:10.1038/s41577-019-0238-0 +227 CL:0011108 CL_0011108 "Colon epithelial cells, also known as colonic epithelial cells, are a specialized type of epithelial cell that constitute the lining of the colon, forming a critical barrier between the body and the harsh luminal environment of the gut. They belong to simple columnar epithelial cells, recognized for their tall and narrow shape, and are among the most rapidly self-renewing tissues in the human body. + +The primary function of colon epithelial cells is to absorb water, electrolytes, and nutrients from the indigestible food matter that reaches the colon. This absorption process is facilitated by microvilli, tiny hair-like structures on the apical surface of the cell that increase its absorptive surface area. These cells also produce mucus, a gel-like substance that lubricates the colon and assists in the movement of waste material. This mucus layer, composed of mucin proteins, serves as the first line of defense against physical damage and pathogenic microorganisms and is key in maintaining gut health. + +Colon epithelial cells also play a vital role in immune function. They can sense pathogens and damage within the lumen and respond by producing a range of antimicrobial compounds to combat foreign invaders. Furthermore, they regulate immune response by maintaining a delicate balance between pro-inflammatory and anti-inflammatory signals to the underlying immune cells. Alterations in the structure or function of colon epithelial cells can lead to various gastrointestinal diseases, like inflammatory bowel disease and colon cancer, indicating their paramount importance in both health and disease." DOI:10.1038/s41586-019-0992-y|DOI:10.1038/nri3608|DOI:10.1038/emm.2017.20 +228 CL:0000131 CL_0000131 "Gut endothelial cells are a crucial component of the endothelium, a thin layer of single cells that line the interior surface of blood vessels and lymphatic vessels, including those in the digestive system or ""gut"". These cells plays an integral role in various physiological and metabolic functions, actively participating in nutrient absorption, host defense, and vascular homeostasis in the gut. + +The primary function of gut endothelial cells lies in their ability to control the passage of materials and the transit of white blood cells into and out of the bloodstream. They achieve this through the formation of a semi-permeable barrier, in which permeability is regulated by tight junctions; complex structures that bring the cells together, sealing the space between them. This ensures a controlled, selective passage of nutrients, ions, and water from the bloodstream into the gut and vice versa, helping maintain homeostasis and overall health. + +Gut endothelial cells also play a significant role in angiogenesis and serve as a critical regulator of the gut immune responses playing a modulative role in gut immune homeostasis and inflammatory responses. In addition, they generate nitric oxide, a potent vasodilator, which helps in maintaining vascular tonus, preventing platelet and leukocyte adhesion, and decreasing smooth muscle proliferation. These multi-faceted roles make gut endothelial cells indispensable for the normal functioning of the gut and overall health." DOI:10.3748/wjg.v17.i5.578|DOI:10.1038/nri2171|DOI:full/10.15252/emmm.202114121|DOI:10.3390/ijms23073698|DOI:10.1111/bph.14527 +229 CL:0002138 CL_0002138 "Endothelial cells of lymphatic vessels are specialized type of cells that form the interior lining of the lymphatic system, which primarily comprises the lymph vessels and nodes. These cells play a critical role in creating a barrier between the lymphatic system and the surrounding tissues. They are structurally different from the endothelial cells of the blood vessels due to the presence of anchoring filaments and lack of a continuous basement membrane, and have a unique phenotype marked by the expression of various cell-specific markers such as Prox-1, VEGFR-3, and LYVE-1. + +A significant function of these endothelial cells is to maintain the fluid balance within the body. They facilitate the uptake of excess interstitial fluid that collects in the body tissues, and ensure its transport back into the bloodstream via the lymphatic vessels. These cells also enable the absorption of fats and fat-soluble vitamins from the digestive system, and their subsequent transport in the form of chyle, a milky fluid, to the blood. + +Furthermore, endothelial cells of lymphatic vessels play a pivotal role in the body's immune response. They enable the passage of lymphocytes, that are crucial for the body's defense mechanism, from the tissues into the lymph where these cells are activated to fight against foreign bodies and infections. Also, they regulate inflammation reactions by controlling the migration of inflammatory cells, and are thus involved in pathological conditions with an inflammatory component. Lastly, these cells have been noted for their involvement in various disease states related to tissue edema, metastasis, and tumor growth, thus highlighting their importance in both health and disease states." DOI:10.3389/fimmu.2019.00036|DOI:10.1016/j.it.2022.10.010|DOI:10.3892/mco.2017.1356|DOI:10.3389/fphys.2020.00509/full|DOI:10.1038/s41577-020-0281-x +230 CL:0002157 CL_0002157 "Endosteal cells, also known as osteogenic cells, are a specialized type of cell that resides in the endosteum of the bone marrow cavity. The endosteum is a thin vascular membrane of connective tissue that lines the inner surface of the bony tissue that forms the medullary cavity of long bones. This specific location assigns endosteal cells critical roles in the bone maintenance and regeneration process as they actively participate in bone remodeling, a process that involves both the formation and resorption of bone tissue. + +Endosteal cells function by regulating the activity of both osteoblasts and osteoclasts. Osteoblasts are cells that deposit new bone, and osteoclasts are responsible for bone resorption, a process important for the maintenance, repair, and remodelling of bones. When new bone tissue is required, such as in instances of bone fractures or increased mechanical stress, endosteal cells differentiate into osteoblasts to facilitate the bone formation process. Conversely, when bone resorption is necessary, these cells are known to release signals that lead to the recruitment and activation of osteoclasts. + +In addition to this, endosteal cells play a significant role in hematopoiesis, which is the formation of blood cellular components. They function in this process by providing a niche for hematopoietic stem cells, serving to support their maintenance and differentiation. Understanding the functionality of endosteal cells is important in the field of regenerative medicine and stem cell therapy, especially in diseases affecting bone remodeling and hematopoiesis. " DOI:10.1182/blood-2009-08-239194|DOI:10.1126/science.75570|DOI:10.1038/leu.2010.214|DOI:10.1182/blood-2004-06-2480|https://www.sciencedirect.com/topics/engineering/endosteum +231 CL:0002139 CL_0002139 "Endothelial cells of the vascular tree, commonly referred to as vascular endothelial cells, line the entire circulatory system, from the heart to the smallest capillaries. These cells have a unique, flattened shape, and are tightly bound together, forming a thin layer known as the endothelium. The endothelium is responsible for maintaining the interior surface of blood vessels, and plays a critical role in ensuring the smooth flow of blood. + +Vascular endothelial cells act as a semi-permeable membrane, controlling the passage of materials and the transit of white blood cells into and out of the bloodstream. These cells are also involved in blood coagulation. When a blood vessel is damaged, endothelial cells promote clotting to prevent excessive bleeding and facilitate wound healing. Other functions include regulation of blood pressure and blood volume by releasing vasodilators and vasoconstrictors to either widen or constrict blood vessels, accordingly. + +Furthermore, the endothelial cells are crucial in the formation of new blood vessels, a process known as angiogenesis. This is particularly important in wound healing and the growth of new tissues during development or after injury. In the context of diseases such as cancer, angiogenesis helps facilitate tumor growth by providing nutrients and oxygen. " https://www.sciencedirect.com/topics/medicine-and-dentistry/vascular-endothelial-cell|DOI:10.1038/s41569-022-00770-1|DOI:10.3389/fphys.2022.863265/full|DOI:10.1186/s12872-015-0124-z +232 CL:0002350 CL_0002350 "Endocardial cells, often referred to as endothelial cells of the heart, constitute the innermost lining layer of the heart tissues, forming the endocardium. They play a critical role in maintaining heart functionality and homeostasis. These cells, flat and squamous in structure, are adjoined closely to form a tight barrier that separates the heart's muscular layer, the myocardium, from the blood flowing through the heart chambers. + +Functionally, endocardial cells are key players in several crucial physiological processes within the heart. Synthesizing matrix molecules that contribute to the structural formation of the heart, these cells actively partake in maintaining its structural integrity. They also exhibit unique metabolic activity, which aids in maintaining optimal cardiac functioning in both healthy and pathological conditions. Importantly, they are known for their involvement in modulating myocardial contraction and relaxation, that is crucial for normal heart rhythm and function. They achieve this by producing factors like nitric oxide (NO) which, amongst other things, aids in the regulation of blood pressure, prevents blood clotting and inhibits the adherence of blood cells to the vessel wall. + +In pathological states, endocardial cells can undergo a transformation process known as endothelial-mesenchymal transition (EndMT), which is inherently involved in several cardiac diseases. In this transition, they acquire the ability to migrate and differentiate into several other types of cells contributing to disease progression. Moreover, their dysfunction can lead to endocarditis, an inflammation of the endocardium, as well as increase the risk of other heart diseases." DOI:10.1016/j.ydbio.2009.06.033|DOI:10.1161/CIRCRESAHA.117.312136|DOI:10.1016/j.medici.2017.08.003|DOI:10.1161/ATVBAHA.121.313788|DOI:10.1101/cshperspect.a036723 +233 CL:0009095 CL_0009095 "The endothelial cell of the uterus is a specialized type of endothelial cell found in the inner lining of blood vessels, specifically those in the uterus. These cells play critical roles in maintaining uterine health, fertilization, and pregnancy processes. They form the interior surface of blood vessels, creating a barrier between the vessel lumen and surrounding tissue. This fluid environment, maintained by these endothelial cells, provides a platform for the material exchange between blood and tissues, thereby modulating blood coagulation, immune responses, and controlling vasodilation and vasoconstriction. + +Functionally, the endothelial cells of the uterus are paramount in regulating the uterine blood flow, an important determinant of successful conception and pregnancy outcomes. They support the vascular changes during the reproductive cycle, particularly the spiral arteriolar development and function, essential in endometrial thickening, maturation, and eventual shedding during menstruation periods. The cells also contribute to angiogenesis, a process crucial during implantation and placenta development, whereby new blood vessels form from pre-existing vessels to supply the growing fetus with oxygen and nutrients. Uterine endothelial cells are also implicated in mediating immune responses within the uterus. Changes in these cells can influence various conditions such as reproductive disorders and complications including heavy menstrual bleeding, endometrial hyperplasia, fertility problems, and cancer." DOI:10.2174/1570161111311050010|DOI:10.1172/jci.insight.163422|DOI:10.1002/cphy.c190015|DOI:10.1111/aji.12128|DOI:10.1530/REP-09-0147 +234 CL:0010008 CL_0010008 "Cardiac endothelial cells are a specialized subset of endothelial cells, the cell type responsible for forming the inner lining of cardiovascular structures such as the heart, and blood vessels. They are a pivotal component of the heart's microenvironment and play a key role in regulating blood pressure, maintaining cardiac homeostasis, in addition to cooperating with other cardiac cells like cardiomyocytes and fibroblasts in the orchestration of a coordinated heart function. + +Cardiac endothelial cells contribute to the each stage of the heart's operation, whether during relaxation or contraction. Cardiac endothelial cells release nitric oxide, a potent vasodilator that regulates blood vessel dilation consequently controlling blood pressure and flow. They also produce a myriad of growth factors that aid in new blood vessel formation, known as angiogenesis, crucially needed for tissue repair and regeneration when the heart undergoes damage, as in cases of myocardial infarction. + +Furthermore, cardiac endothelial cells control the passage of nutrients, hormones, and gases between the bloodstream and the heart tissue, ensuring its complex metabolic demands are met adequately. They serve as a selective barrier, regulating the transit of cells and signaling molecules, thereby playing a pivotal role in inflammatory responses and immune cell trafficking. They also contribute to the maintenance of blood fluidity and clotting balance through a complex interplay of anti-thrombic and pro-thrombic factors. " DOI:10.3389/fcvm.2018.00101|DOI:10.3389/fphys.2018.00382|DOI:10.1530/VB-20-0006|DOI:10.3390/ijms20184411|DOI:10.1007/s00441-021-03471-2 +235 CL:1000398 CL_1000398 "Endothelial cells of hepatic sinusoids, also known as hepatic or liver sinusoidal endothelial cells (HSEC or LSEC), are unique, specialized type of endothelial cells located in the liver. They are the building units of the hepatic sinusoid, which functions as a specialized capillary system that facilitates the exchange of various substances between the blood and hepatocytes. This finely tuned environment, facilitated by HSEC, is primordial for the liver's multiple physiologic functions that include nutrient metabolism, toxin inactivation, and immunomodulation. + +The HSEC have a distinctive morphology that sets them apart from the typical endothelial cells found in other organs. These cells are exceptionally thin to allow for efficient transfer of molecules and characterized by fenestrations, which are non-diaphragmatic, sieve-like openings that provide an open filtration pathway from the sinusoidal lumen to the space of Disse, where hepatocytes are exposed. The fenestration is a crucial feature that allows lipoproteins, nutrients, and other plasma components easy access to hepatocytes for essential liver functions, including clearance of waste products and metabolic regulation. + +HSECs further play a vital role in immune functionality in the liver. They act as a sentinel, determining the nature of the immune response to encountered particulates. They possess a capacity for antigen presentation and express a series of immune-related surface molecules, which helps in immunosurveillance and immunoregulation. The HSEC also aid in the removal and destruction of virus-infected cells, harmful microorganisms, and circulatory waste products to safeguard liver health and general systemic cleanliness. " DOI:10.1016/j.jhep.2016.07.009|DOI:10.1038/s41575-018-0020-y|DOI:10.1038/s41575-020-00411-3|DOI:10.1038/cmi.2016.5|https://www.sciencedirect.com/topics/immunology-and-microbiology/disse-space +236 CL:1000850 CL_1000850 "Macula densa epithelial cells, as part of the complex nephron structure, play a crucial role in kidney function. These cells, which make up the macula densa, help regulate blood pressure and the filtration rate of the glomerulus by sensing sodium chloride amounts in the kidney tubules. Found where the thick ascending limb of the Loop of Henle touches the afferent arteriole, macula densa epithelial cells are positioned in an optimal location to monitor and respond to changes in the filtrate composition. + +These cells maintain intraglomerular homeostasis. When the sodium chloride concentration is high, macula densa cells respond by secreting adenosine and vasoconstricting the afferent arteriole to decrease the glomerular filtration rate. Conversely, if the sodium chloride concentration in the filtrate is low, the production and release of nitric oxide cause vasodilation to enhance the glomerular filtration rate. + +Macula densa epithelial cells also have a role in tubuloglomerular feedback mechanisms, an essential autoregulatory renal response. They send feedback to the glomerular mesangial cells, allowing constriction or relaxation of the afferent arteriole as needed depending on the content of the filtrate." DOI:10.1146/annurev-physiol-052521-121841|DOI:10.1073/pnas.0736323100|DOI:10.1681/ASN.2009070759|DOI:10.1161/HYPERTENSIONAHA.115.04739|DOI:10.1681/ASN.2015050515 +237 CL:1000849 CL_1000849 "Kidney distal convoluted tubule epithelial cells, often referred to simply as distal convoluted tubule (DCT) cells, constitute a significant portion of the nephron -- the functional building unit of the kidney involved in filtration and reabsorption of substances from blood. The DCT epithelial cells form lining of the distal convoluted tubule, a segment of the nephron located after the loop of Henle and before the collecting tubule. These cells are characterized by unique morphological features such as small size, low height and fewer microvilli compared to proximal convoluted tubule epithelial cells. + +These cells perform a host of vital functions contributing to the regulation of extracellular fluid volume and electrolyte balance, blood pressure and pH. While the DCT is less prominent in water and sodium reabsorption compared to the proximal tubule and the loop of Henle, it plays a crucial role in fine-tuning the process. DCT epithelial cells are responsible for the final adjustments of sodium, potassium and calcium reabsorption, thereby affecting overall fluid and electrolyte balance, blood pressure regulation and bone health. The reabsorption process is regulated by hormones including aldosterone and parathyroid hormone. + +The distal convoluted tubule (DCT) also plays a significant role in acid-base homeostasis by secreting protons (H+) into the tubular fluid and reabsorbing bicarbonate ions (HCO3-), thus regulating the pH of the blood. The ability of DCT cells to adjust urine concentration plays a part in maintaining the body’s pH balance and preventing conditions like acidosis or alkalosis. In summary, kidney distal convoluted tubule epithelial cells perform functions that are crucial to maintaining body's homeostasis. " DOI:10.1681/ASN.2019040415|DOI:10.1002/cphy.c140002|DOI:10.2215/CJN.05920613|DOI:10.1007/s40620-021-01032-y|DOI:10.1152/physrev.2000.80.1.277 +238 CL:1000909 CL_1000909 "Kidney loop of Henle epithelial cells are specialized cells located within the nephron, the core functional structures of the kidneys, responsible for maintaining body fluid homeostasis. These cells constitute the convolutional structure coined as the Loop of Henle and play a key role in the reabsorption of water and solutes to finely tune the concentration of urine. The Loop of Henle has two segments - the descending limb (which is permeable to water but not to salt) and the ascending limb (which is permeable to salt but not water). Both segments contain important epithelial cells that manage this reabsorption process. + +The epithelial cells lining the descending limb of the Loop of Henle are known for their high permeability to water, which secretively moves out into the hyperosmolar medullary interstitium, leading to the concentration of the filtrate. This segment is usually thin and comprises a simple squamous epithelium. The cells in the ascending limb, in contrast, actively extrude sodium, potassium and chloride ions into the interstitium of the kidney, making the filtrate hypoosmotic by the time it leaves the ascending limb. These cells have a high metabolic demand, as reflected in the copiousness of the mitochondria and complex system of intracellular membranes they contain. + +The environment within each segment of the Loop of Henle is critical in enabling these specialized epithelial cells to perform their tasks. Variations in these cells allows them to perform distinct physiological roles, ranging from the passive flux of water in the descending limb to mechano-electrical transduction and active transport of solutes against concentration gradients in the ascending limb." DOI:10.2215/CJN.04480413|DOI:10.1007/s101570050002|DOI:10.1016/j.biocel.2005.02.007|DOI:10.2147/IJNRD.S154000|https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/loop-of-henle +239 CL:1001016 CL_1001016 "The kidney loop of Henle ascending limb epithelial cell, also commonly referred to as the thick ascending limb (TAL) cell, plays an instrumental role in the function of the nephrons within the kidney. Located specifically in the ascending limb of the loop of Henle, these cells are central in the process of urine formation. They are distinguished by their cuboidal to low columnar shape which allows or aids in the reabsorption of solutes from the filtrate that passes through the nephrons. + +The main function of these cells is to actively reabsorb sodium, potassium, and chloride ions back into the bloodstream, thereby regulating electrolyte balance, blood pH, and overall fluid balance in the body. It ensures that valuable molecules, such as glucose and amino acids, are not excreted via urination but rather reabsorbed into the bloodstream. Through a process of active transport, these cells move these ions against their concentration gradients via the Na+-K+-2Cl- symporter located in their apical membrane (part of the cell that faces the lumen of the nephron). +" DOI:10.2215/CJN.04480413|DOI:10.2147/IJNRD.S154000|DOI:10.2215/CJN.04480413|DOI:10.1152/ajprenal.00261.2019 +240 CL:1001021 CL_1001021 "The kidney loop of Henle descending limb epithelial cells are highly specialized cells that play a crucial role in maintaining the body's salt and water balance. These cells line the descending limb of the loop of Henle, which is a portion of the renal tubule located in the kidneys, an organ responsible for filtering waste products, ions and extra water from the blood and converting them into urine. However, the descending limb epithelial cells are specifically involved in the countercurrent multiplication system, a mechanism to concentrate urine that involves both active and passive transport processes. + +These cells are notably permeable to water but relatively impermeable to solutes, a characteristic that dramatically influences the osmotic gradient in the renal medulla. As filtrate initially descends down the loop of Henle, water gets drawn out due to the increasing osmotic gradient, thereby concentrating the filtrate. Additionally, these epithelial cells are exceptionally thin walled, allowing water to freely diffuse across the membrane. + +Furthermore, the kidney loop of Henle descending limb epithelial cells are inextricably linked to the functioning of numerous diuretic drugs, which work by blocking the reabsorption of water and certain electrolytes in the kidneys, leading to increased urine production to rid the body of excess fluids. " DOI:10.1007/s00360-018-1164-3|DOI:10.1146/annurev-physiol-021113-170350|DOI:10.1152/advan.00227.2022 +241 CL:1001106 CL_1001106 "The kidney loop of Henle thick ascending limb epithelial cell, also known as a ""thick ascending limb (TAL) cell"", is a specialized cell type primarily located in the nephrons of the kidney, in a structure known as the loop of Henle. These cells, comprising the tubular duct of the nephron's ascending limb, play an important role in maintaining the body's proper electrolyte and fluid balance. They form a unique barrier that allows selective permeability, enabling the kidney's function of urine concentration and reabsorption of electrolytes. + +TAL cells are responsible for the active reabsorption of sodium, chloride, and potassium ions. This is achieved through an ion co-transport mechanism facilitated by various transporters such as the Na-K-2Cl cotransporter located on the basolateral membrane of the cell. This cotransporter moves these ions from the tubular fluid into the cell, while a Na-K ATPase pump on the basolateral membrane subsequently expels the sodium into the interstitial fluid, helping maintain a low intracellular sodium concentration. Through this mechanism, TAL cells contribute substantially to the regulation of plasma pH, volume, and blood pressure." DOI:10.2147/IJNRD.S154000|DOI:10.1152/ajprenal.00261.2019|DOI:10.2215/CJN.04480413|DOI:10.1161/HYPERTENSIONAHA.108.120246|DOI:10.1152/ajprenal.00396.2011 +242 CL:1001602 CL_1001602 "Cerebral cortex endothelial cells are unique endothelial cells responsible for the formation and regulation of the blood-brain barrier (BBB), a specialized structure that separates the circulating blood from the cerebral neural tissue. These cells line the inner surface of nearly all blood vessels that irrigate the cerebral cortex, the outermost layer of the brain involved with complex cognitive functions such as thought, perception, and memory formation. Cerebral cortex endothelial cells are integral to maintaining brain health and function due to their role in regulating brain microenvironment and controlling the passage of essential molecules and cells. + +The endothelial cells in the cerebral cortex are distinctive due to their highly selective permeability, largely attributable to the existence of unique tight junctions which maintain the barrier function of the BBB. The tightly interconnected structures of these cells prevent most substances from freely diffusing into the brain tissue, ensuring that harmful agents such as toxins, pathogens, or peripheral immune cells don't reach the brain and compromise its function. These cells also express multiple transporters and enzymes, allowing the selective entry of necessary nutrients and metabolites while excluding toxic substances. + +Cerebral cortex endothelial cells also participate in neurovascular coupling, a process where localized neuronal activity increases cerebral blood flow to satisfy the local metabolic demands. The endothelial cells work in coordination with neurons and other cell types such as astrocytes and pericytes to mediate this process. They have been thought to regulate local blood flow by releasing substances in response to neuronal activity. Additionally, these cells are involved in many pathological conditions. Breakdown or dysfunction of the BBB often marked by altered endothelial cell function is linked to numerous neurological disorders including stroke, multiple sclerosis, Alzheimer’s disease, and brain tumors." DOI:10.1186/s12987-020-00230-3|DOI:10.1038/nbt.2247|DOI:10.3389/fnins.2023.1047778|DOI:10.1038/nrn1824|DOI:10.1177/0271678X156179 +243 CL:2000011 CL_2000011 "A dermis lymphatic vessel endothelial cell is a specialized type of cell that lines the interior surface of lymphatic vessels present in the dermal layer of the skin. These cells are organized into a single layer, forming an integral part of the lymphatic system which acts as the body's secondary circulatory system. The primary function of dermis lymphatic vessel endothelial cells is to facilitate the transportation and regulation of the lymph fluid within the dermis. They act as a barrier, contributing to fluid homeostasis, lipid transport, and immune cell trafficking. These cells are uniquely equipped to let fluid and larger molecules, including proteins and immune cells, into the lymphatic vessels from the surrounding interstitial space. This is enabled by the specialized junctions between the endothelial cells and the presence of primary lymphatic valves that prevent the backflow of lymph. + +Another paramount role of dermis lymphatic vessel endothelial cells is their involvement in immune response. By interacting with white blood cells, especially T-cells and dendritic cells, they can mediate local immune surveillance and contribute to both innate and adaptive immune responses. These cells are also implicated in a variety of pathological conditions, including lymphedema and metastasis in cancer. " DOI:10.3389/fphys.2020.00509|DOI:10.1038/s41423-023-01042-9|DOI:10.3389/fimmu.2023.1235812|DOI:10.1038/s41467-019-14127-9|DOI:10.3389/fphys.2020.577584 +244 CL:0002262 CL_0002262 "Endothelial cells of sinusoids, often referred to as sinusoidal endothelial cells (SECs), are a specialized type of endothelial cell that primarily reside in the capillaries of the liver, spleen, and bone marrow. These cells form the innermost monolayer of the sinusoidal blood vessels, also known as sinusoids, that mediate the exchange of nutrients, metabolites, and waste materials between the blood and the surrounding organ tissue. SECs possess distinctive morphological features including a large, flattened shape, an abundance of fenestrations or pores, and the lack of a continuous basement membrane. These structural characteristics distinguish sinusoidal endothelial cells from other, more regularly structured endothelial cells in the body. + +Due to their special fenestrated structure, SECs facilitate the exchange of macromolecules, like lipoproteins and hyaluronan, between plasma and the surrounding organ parenchymal cells. These fenestrations act like sieves, allowing the passage of substances based on their size and charge. It's noteworthy that the permeability characteristics of SECs can be regulated dynamically according to the body's homeostatic needs. + +Beyond their key role in exchange mechanisms, endothelial cells of sinusoids are involved in several other functions. In the liver, for example, they help in the removal and endocytic degradation of waste macromolecules, immune response, and regulation of liver regeneration. They also participate in the formation and remodeling of blood vessels, a process known as angiogenesis. Additionally, in recent years, it has been discovered that these cells may have a role in disease conditions like cirrhosis and liver cancer." DOI:10.1007/s10456-021-09780-y|DOI:10.1038/s41575-018-0020-y|DOI:10.1186/1476-5926-1-1|DOI:10.1016/j.jhep.2016.07.009|DOI:10.1038/s41598-020-57652-0 +245 CL:0019022 CL_0019022 "Endothelial cells of pericentral hepatic sinusoids are a specific type of endothelial cells located in the pericentral region of the hepatic sinusoids, an intricate network of small vessels within the liver. These cells lining in the smallest vessels in the liver (intralobular sinuses or hepatic sinusoids) form a semi-permeable barrier between the blood and liver parenchymal cells. They exemplify the concept of a specialized endothelium due to their unique structural and functional characteristics. + +Structurally, these cells are thin and extremely flat, facilitating rapid exchange of various substances with their surrounding environment. Moreover, they lack a conventional basement membrane, which furnishes them with the capacity for easier exchange between the sinusoidal lumen and the cells of the hepatic tissue, especially hepatocytes. Endothelial cells of pericentral hepatic sinusoids have larger fenestrations compared with periportal sinusoidal endothelial cells, which are believed to permit easier transendothelial transfer of specific lipoproteins. + +Functionally, endothelial cells of pericentral hepatic sinusoids significantly contribute to regulating blood flow within the liver and play a notable role in facilitating the transportation of nutrients, metabolites, and waste products between the bloodstream and hepatocytes. They also participate in various liver-specific functions such as endocytosis, bile secretion, and immune response. In addition, these cells contribute to the metabolic zonation within the liver, a functional specialization where different metabolic processes are performed in different spatial regions. Further, these cells also play an integral role in liver regeneration and repair through their ability to promote hepatocyte proliferation and modulate inflammation and fibrosis. " DOI:10.3748/wjg.v12.i34.5429|DOI:10.1016/j.jhep.2016.07.009|DOI:10.3389/fphys.2021.732929|DOI:10.1172/JCI66025|DOI:10.1016/j.jhep.2016.07.009 +246 CL:1001006 CL_1001006 "Kidney afferent arteriole cells are specialized cell types found in the renal vasculature, specifically in the afferent arterioles which help in maintaining the renal blood flow and glomerular filtration rate. They are essential for the proper functioning of the kidneys, contributing to the regulation of blood pressure and fluid balance within the organism. Located before the glomerulus, a tiny, intricate network of capillaries within the nephron, these cells help control the expansion or contraction of the arteriole, thus regulating the pressure and flow of blood into the glomerulus. + +Functionally, kidney afferent arteriole cells are largely involved in responding to changes in blood volume and systemic blood pressure. They achieve this by modulating the diameter of the afferent arteriole through a process known as autoregulation. Autoregulation involves two primary mechanisms: the myogenic response and the tubuloglomerular feedback. The myogenic response is essentially the intrinsic ability of the vascular smooth muscle to respond to pressure changes, while the tubuloglomerular feedback is the process where the macula densa cells located near the glomerulus respond to changes in fluid delivery rates in the tubules, sending signals to afferent arterioles to constrict or dilate accordingly. These cells also have significant interaction with renin-containing juxtaglomerular cells, which are located in the wall of afferent arterioles. Juxtaglomerular cells secrete the enzyme renin in response to low blood pressure or sympathetic nerve activity, initiating the renin-angiotensin-aldosterone system cascade that ultimately helps retain sodium and water to increase blood volume and pressure." DOI:10.1152/physrev.00042.2012|DOI:10.1007/s00424-012-1126-7|DOI:10.2174/15701611113116660149|DOI:10.1152/ajpregu.00332.2006 +247 CL:1001009 CL_1001009 "Kidney efferent arteriole cells are highly adaptable vascular cells that make up the efferent arterioles in the kidney. These units are integral components of the renal microcirculation system, conducting blood away from the glomeruli after filtration occurs. Efferent arterioles directly affect glomerular hydrostatic pressure and, subsequently, the rate of glomerular filtration. They are the downstream channels that ensure the effective transportation of blood to the peritubular capillaries and vasa recta, critical for maintaining fluid balance and electrolyte homeostasis. + +Kidney efferent arteriole cells are exceptional in their ability to perform autoregulation—a critical dynamic control of intrarenal blood flow ensuring stable glomerular filtration rates. This is primarily achieved via myogenic and tubuloglomerular feedback mechanisms, where the cells respond to changes in pressure and the concentration of sodium chloride in the tubular fluid, and constrict or dilate depending on the detected changes. + +Cells associated with the efferent arteriole also respond to several systemic influences. Through complex intracellular signaling pathways, they respond to fluctuations in hormones (like angiotensin II and endothelin) and several other mediators such as nitric oxide and prostaglandins. Their adaptive capability helps maintain homeostasis and ensures the entire system's optimal performance under various physiological conditions. Dysfunctions in kidney efferent arteriole cells can lead to severe pathologies like hypertension and chronic kidney disease." DOI:10.3748/wjg.v12.i34.5429|DOI:10.1152/physrev.00042.2012|DOI:10.1159/000072054|DOI:10.1161/01.HYP.29.1.222|DOI:10.1152/ajpregu.2000.279.2.R629 +248 CL:0000129 CL_0000129 "Microglial cells, sometimes referred to as microglia, are a type of glial cell that primarily exist within the central nervous system (CNS), notably in the brain and the spinal cord. Classified among the resident immune cells, microglial cells represent about 10% of all cells found within the CNS. These cells are derived from progenitor cells in the yolk sac, which differentiates them from other types of glial cells (such as astrocytes and oligodendrocytes) that are derived from neuroectodermal cell lineages. + +The primary role of microglial cells is to act as the first and main active form of immune defense in the CNS. They express a vast repertoire of pattern recognition receptors, which allow them to sense and eliminate microbes invading the CNS parenchyma. They represent one of the macrophage populations of the CNS and are responsible for phagocytosis (engulfing and destroying cellular waste or pathogens) in the neural environment. + +Microglial cells are particularly responsive to pathogens and injuries and change their morphology in reaction to inflammation or insult: In the normal state they are characterized by a ramified shape with small processes; in response to stimuli, some microglia mature and change to an amoeboid shape. + +Beyond their macrophagic activity, they also perform synaptic pruning during brain development, eliminate unnecessarily produced neurons, and facilitate tissue regeneration and repair. they play integral roles in regulating neural development and supporting cell survival and are important for maintaining tissue homeostasis. + +While their protective role generally benefits the brain, their over-activation can occasionally lead to neuro-inflammatory diseases, underlining the importance of balanced microglial cell functions. They have been extensively studied for their association with neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. +" DOI:10.1038/nri3086|DOI:10.3389/fnins.2021.742065|DOI:10.1016/j.cell.2019.08.053|DOI:10.1016/j.tins.2021.11.001|DOI:10.1016/j.conb.2022.102674 +249 CL:0000878 CL_0000878 "Central Nervous System (CNS) macrophages represent an integral part of the brain's innate immune system. These immune cells play crucial roles in maintenance and regulation, homeostasis, and disease response, thereby helping in the overall cognitive functioning of an organism. + +There are different macrophage populations in the CNS, often classified into microglial cells, which reside in the parenchyma, and non-parenchymal macrophages at the interface between the brain and the periphery, including the perivascular spaces, the choroid plexus, and the meninges. CNS macrophages are derived from erythromyeloid progenitors in the yolk sac. CNS macrophages have distinct morphologies: Meningeal and perivascular macrophages have a more elongated shape than microglia, which are characterized by a small cell body with fine processes; in contrast, choroid plexus macrophages typically have a stellate shape. + +Microglia are the most abundant abundant mononuclear phagocytes and have been shown to play a number of physiological roles, including proinflammatory and anti-inflammatory functions, synaptic pruning and remodeling, and apoptotic cell removal through phagocytosis. Non-parenchymal CAMs primarily support the barrier function against external antigens. Meningeal macrophages have been shown to respond to peripheral microbial challenges and to protect the brain against fatal viral infection. + +CNS macrophages are also involved in the initiation and progression of many neurological diseases, such as Alzheimer's disease and Parkinson's disease as well as multiple sclerosis. +" DOI:10.1007/s00281-013-0382-8|DOI:10.1038/s41583-019-0201-x|DOI:10.1016/j.immuni.2022.10.005|DOI:10.1016/j.tins.2021.07.002 +250 CL:0002629 CL_0002629 "Mature microglial cells represented one of the macrophage populations within the central nervous system (CNS). Microglial cells serve as the primary immune defense mechanism within the CNS, playing active roles in maintaining brain homeostasis and responding to pathological processes. In response to pathogens and injuries, microglial cells mature and change their morphology from a ramified shape with small processes (normal state) to an amoeboid shape (mature state). + +Mature microglial cells possess multiple functional abilities, thereby enabling them to execute diverse roles in order to maintain the health of surrounding neural cells. They act to clear away cellular debris, dead neurons, or plaque formations through the process of phagocytosis. They are also continuously scanning their environment and are able to detect subtle changes in the neural landscape caused by injury, disease, or infection. Upon detection of such changes, these cells become activated and present antigens and secrete cytokines and chemokines to initiate an inflammation response, which sustains the brain’s defense against injurious agents. + +Their role is not solely destructive or defensive: mature microglial cells also contribute to neurodevelopment by guiding the formation of neural circuits, synaptogenesis, and remodeling. Furthermore, they assist in managing synaptic plasticity, a key process in learning and memory functions. While the dysregulation of microglial cells has been implicated in various neurodegenerative diseases, they are also regarded as potential therapeutic targets for such conditions, given their crucial roles in maintaining CNS health. +" DOI:10.4103/1673-5374.226386|DOI:10.1111/j.1745-7254.2007.00625.x|DOI:10.3389/fimmu.2022.997786|DOI:10.1111/jnc.15689|DOI:10.4103/1673-5374.322423 +251 CL:0009038 CL_0009038 "Colon macrophages are a heterogeneous population of macrophages in the gastrointestinal tract. Intestinal macrophages represent the largest group of macrophages in the body and play a key role as sentinels for pathogen recognition and elimination. Because the gastrointestinal tract is continually exposed to a high antigenic load derived from microbes and food intake, macrophages in the intestines are crucial not only for the gut’s immune defense but also for maintaining gastrointestinal homeostasis, avoiding chronic inflammation despite constantly facing foreign antigens. The phenotypic profiles and cytokine production of intestinal macrophages therefore differ from conventional macrophages elsewhere in the body. + +Colon macrophages orchestrate a wide variety of immune responses. They interact with the colon’s microflora thanks to their location in the mucosal layer, thus playing an important role in shaping gut immunity. By presenting antigens, they help to activate and steer an appropriate immune response either by triggering inflammation against harmful pathogens or by supporting tolerance for beneficial microbes. Therefore, disturbances in the colon macrophage population is thought to contribute to colon-related diseases such as inflammatory bowel disease and colon cancer. + +These immune cells are versatile and multifunctional, not just limited to defensive actions. Colon macrophages interact with the enteric nervous system to regulate gut secretion and motility. They also play a crucial role in maintaining colon tissue health and integrity by contributing to tissue repair processes. This occurs either through phagocytosis of dead cells and remnants, or indirectly through the release of growth factor molecules, which stimulate cellular proliferation and differentiation necessary for tissue regeneration. +" DOI:10.1016/j.jcmgh.2021.08.021|DOI:10.1038/s41575-019-0172-4|DOI:10.1038/s41575-023-00769-0|DOI:10.1016/j.immuni.2022.08.005 +252 CL:1000698 CL_1000698 "Kidney resident macrophages are a heterogeneous population of immune cell found in the cortex and medullary regions of the kidney as well as within and surround the glomeruli. Their primary role involves maintaining homeostasis and immune surveillance in the kidney microenvironment, defending against ascending urinary infections. Beyond traditional macrophage roles such as phagocytosis and antigen presentation, kidney resident macrophages also contribute significantly to the response to kidney injury including tissue repair and angiogenesis. + +Under normal physiological conditions, kidney resident macrophages work to maintain the balance of the kidney's microenvironment by removing dead cells, pathogens and cellular debris, to limit inflammation and tissue damage. They are ‘professional’ phagocytes, clearing pathogens and debris by engulfing and digesting these harmful materials. Moreover, they are capable of presenting antigens to other immune cells, which aids in the activation of the adaptive immune response. +Kidney resident macrophages show a high degree of plasticity: in response to environmental stimuli they change their morphology and cell surface markers. For example, in response to acute injury, some macrophages adopt a pro-inflammatory phenotype and augment tissue damage; once the injury stimulus is removed, they may change to mediate tissue repair. + +While kidney macrophages contribute to wound healing, tissue repair and regeneration by producing key growth factors and cytokines that stimulate cell proliferation, collagen production, and blood vessel formation, dysregulation in their activity can also lead to progressive inflammation and fibrosis, common features in chronic kidney disease. +" DOI:10.1172/jci.insight.161078|DOI:10.3389/fphys.2017.00837|DOI:10.3389/fimmu.2021.681748|DOI:10.1016/bs.ircmb.2022.01.005 +253 CL:0000092 CL_0000092 "Osteoclasts, derived from the monocyte/macrophage lineage, play a crucial role in bone remodeling through bone resorption. They are distinguished from other cells by their large size and their unique ability to secrete enzymes and acids that dissolve the calcium phosphate in bone. The formation of osteoclasts is influenced by two primary factors: macrophage colony-stimulating factor (M-CSF) and the ligand-activated receptor (RANKL) of nuclear factor kappa B (NF-κB). + +Osteoclasts also collaborate with osteoblasts, responsible for new bone formation, to maintain bone health and adapt bone structure. Their coordinated actions allow continuous remodeling while preserving overall bone strength and integrity. Imbalances in osteoclast activity can lead to pathological conditions. For example, excessive activity may contribute to diseases like osteoporosis, periprosthetic osteolysis, bone tumors, and Paget's disease. Other the other hand, osteoclast deficiency ca result in conditions like osteopetrosis." https://www.sciencedirect.com/topics/medicine-and-dentistry/osteoclast|DOI:10.3389/fmed.2017.00234|DOI:10.37175/stemedicine.v1i4.57 +254 CL:0000557 CL_0000557 "Granulocyte monocyte progenitor cells (GMP cells), originating from hematopoietic stem cells in the bone marrow, are a critical intermediate in myeloid cell development. Positioned at a key differentiation juncture, these cells exhibit bidirectional potential, giving rise to both granulocyte and monocyte lineages. + +Their primary role is to generate mature granulocytes and monocytes, essential components of the body's innate immunity and inflammatory responses. Granulocytes, such as neutrophils, eosinophils, and basophils, contribute to the first line of defense against infections by migrating to the infection site and phagocytosing pathogens. Monocytes can differentiate into macrophages or dendritic cells, playing diverse roles in immune responses. " DOI:10.1016/j.immuni.2017.10.021|DOI:10.1186/2050-7771-2-1|DOI:10.1146/annurev-immunol-081022113627 +255 CL:0002092 CL_0002092 "Bone marrow contains stem cells, including hematopoietic stem cells (HSCs), and can be found in larger bones such as the pelvis, femur, and hip. They are unique in their ability to self-renew and differentiate, that is, they can generate daughter cells identical to themselves and also give rise to cells that will differentiate into a wide variety of other cell types. + +A crucial function of bone marrow cells is the production of blood cells, a process known as hematopoiesis. These cells possess the capability to differentiate into every type of blood cell - red blood cells, white blood cells, and platelets. Red blood cells (erythrocytes) primarily carry oxygen throughout the body, while white blood cells (leukocytes) form the primary elements of the immune system, aiding in defending the body against infection and disease. Platelets play a vital role in blood coagulation, an essential process that stops excessive bleeding when injuries occur. + +Furthermore, bone marrow cells have a significant regenerative capacity, making them fundamental in treating certain kinds of diseases and health disorders, like leukemia and other forms of cancer, through bone marrow transplant. In this procedure, healthy bone marrow cells from a donor are introduced to a recipient with malfunctioning bone marrow cells. These donor cells then repopulate the recipient’s bone marrow and restore its normal function. Overall, bone marrow cells play a pivotal role in maintaining the body’s overall health and function by ensuring a steady and healthy supply of vital blood cells and possessing exceptional regenerative capabilities." DOI:10.1038/s41580-019-0103-9|https://www.ncbi.nlm.nih.gov/books/NBK27092/|https://www.ncbi.nlm.nih.gov/books/NBK534246/|https://www.ncbi.nlm.nih.gov/books/NBK536951/ +256 CL:0007010 CL_0007010 "Preosteoblast is a critical cell type involved in bone formation, crucial in a process known as ossification or osteogenesis. They are derived from mesenchymal stem cells and are an intermediate stage marking the transition from an osteoprogenitor cell to a fully differentiated osteoblast. The presence of preosteoblasts signifies the site of new bone deposition, highlighting their crucial role in skeletal development and in response to bone injury repairs. + +The primary function of preosteoblasts is to differentiate into osteoblasts, which are responsible for secreting osteoid (the unmineralized portion of bone matrix) and regulating the process of bone mineralization. Preosteoblasts are regulated by various growth factors and hormones, including bone morphogenic proteins (BMPs), fibroblast growth factors (FGFs), parathyroid hormone (PTH) and Vitamin D. + +However, the function of preosteoblasts is not limited to bone formation alone. In addition to osteogenesis, preosteoblasts significantly contribute to the maintenance of bone homeostasis through regulating the activity of osteoclasts - the cells responsible for bone resorption. This regulation is mediated through RANK/RANKL/OPG pathway signaling. Osteoprotegerin (OPG) released from the preosteoblasts acts as a decoy receptor for RANKL impairing osteoclast formation, hence preventing excessive bone resorption. This regulatory role indicates the dual functionality of preosteoblasts, which are indispensable for both the formation of new bone and the maintenance of existing bone tissue. +" DOI:10.12659/MSMBR.901142|DOI:10.1038/srep32884|DOI:10.1096/fba.2020-00058|DOI:10.1210/endo.141.9.7634 +257 CL:0000114 CL_0000114 "Surface ectoderm cells give rise to external structures such as the epidermis, hair, nails, and sweat glands. They are critical during the early stages of embryonic development, where they delineate and create the organism's exterior body plan. Beyond forming the organism's physical exterior, surface ectodermal cells have other significant roles. For instance, these cells lead to the development of the anterior pituitary gland and the enamel of the teeth. They are also integral to the formation of the sensory organs, including the eyes and the ears. In the eyes, they form the cornea and lens epithelium. In the ears, they form the external ear canal and certain parts of the inner ear. Therefore, these cells are instrumental in the development of various sensory systems in an organism. + +Certain abnormalities or mutations in surface ectodermal cells could lead to medical conditions known as ectodermal dysplasias. These are a group of inherited disorders affecting the development or function of teeth, hair, nails, and sweat glands. Therefore, understanding the formation and function of surface ectodermal cells is also important in identifying and addressing certain genetic disorders and conditions. In summary, surface ectodermal cells are essential in embryonic development, contributing to the creation of the external physical appearance and the sensory organs of an organism." DOI:10.1038/srep32007|https://www.ncbi.nlm.nih.gov/books/NBK539836/|https://www.ncbi.nlm.nih.gov/books/NBK563130 +258 CL:0000222 CL_0000222 "Mesodermal cells are pluripotent and the most abundant in the human body. They contribute to the development of several structures such as the skeletal muscles, bones, heart and blood vessels, kidneys, gonads, connective tissues, and certain layers of the skin. Hence, the mesoderm is often regarded as an active and diverse layer due to its role in forming many bodily structures. + +In embryonic development, these cells are instrumental, contributing to the body's structures through a carefully coordinated sequence of morphogenetic movements. This process forms the complex multicellular architecture of tissues and organs from a simple ball of cells. Without the function of mesodermal cells, the body's integral structures and systems would cease to form correctly, leading to developmental disorders such as axial mesodermal dysplasia complex" DOI:10.1016/j.ceb.2019.07.012|DOI:10.5535/arm.2016.40.1.162|https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/mesoderm +259 CL:0000148 CL_0000148 "Melanocytes are specialized cells prevalently found in the skin, but also present in the hair follicles, eyes, inner ear, bones, heart, and brain. Their primary function is the synthesis of melanin, a pigment responsible for coloration of skin, hair, and eyes. The presence and distribution of this pigment play a crucial role in the body's defense mechanism against harmful ultraviolet radiation. + +In addition to melanin production, melanocytes also engage in a variety of other biological functions. They play a fundamental role in the immune response, owing to their ability to present antigens to T cells. Furthermore, they contribute to the maintenance of the skin's homeostasis by regulating processes such as extracellular matrix remodeling and cytokine production. A balance in melanocyte function is pivotal, as dysfunctions often result in dermatological disorders. For instance, the loss of melanocytes or reduction in their function may lead to hypopigmentation conditions such as vitiligo, whereas an abnormal increase could result in hyperpigmentation disorders or melanoma, a dangerous type of skin cancer." https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/melanocyte|DOI:10.1111/j.1751-1097.2007.00226.x|DOI:10.3390/ijms21249769|DOI:10.1002/med.21754|DOI:10.1038/nrc.2016.37 +260 CL:1000458 CL_1000458 "Melanocytes of the skin are specialized pigment cells crucial for producing and distributing melanin, the pigment determining skin, in addition to hair and eye color. Located in the basal layer of the epidermis, melanocytes serve as a natural sunscreen, protecting skin cells from harmful UV radiation. Structurally dendritic, they synthesize melanin through melanogenesis, transferring melanosomes to keratinocytes for UV shielding + +Beyond pigmentation and UV protection, melanocytes play roles in immune and inflammatory responses. They respond to environmental changes, communicate with skin cell types, and secrete cytokines and growth factors influencing skin homeostasis. Dysregulation may lead to pigment disorders like vitiligo and melasma or contribute to skin cancer, particularly malignant melanoma." DOI:10.5114/pdia.2013.33376|https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/melanocyte|DOI:10.1111/j.1751-1097.2007.00226.x|DOI:10.1016/j.jinf.2015.06.006|DOI:10.1615/CritRevEukaryotGeneExpr.2020028454 +261 CL:0000190 CL_0000190 "Fast muscle cells, also known as type II muscle fibers, are a particular type of muscle cell that specializes in conducting rapid, high-intensity contractions. These cells are primarily found within skeletal muscle groups that are directly involved in gross motor activities, such as running, jumping, or lifting heavy weights. The designation ""fast"" refers to their speed of contraction in response to neural stimuli, which is significantly quicker when compared to other muscle cell types such as slow-twitch or type I muscle fibers. + +The primary function of fast muscle cells revolves around their role in anaerobic metabolism, which provides the energy needed for short, forceful bursts of power. They contain a high concentration of glycolytic enzymes that facilitate this process, leading to a swift break down of glucose to generate ATP (adenosine triphosphate), the primary energy currency in biological systems. On the downside, the byproduct of this very rapid, anaerobic metabolic process is lactic acid, which can build up and cause muscle fatigue. + +Fast muscle cells can be further classified into two subtypes based on their metabolic characteristics: type IIa and type IIb/x. Type IIa cells, also known as fast oxidative-glycolytic fibers, possess a good oxygen supply and can function in both anaerobic and aerobic conditions, exhibiting moderate resistance to fatigue. On the other hand, type IIb/x cells, also known as fast glycolytic fibers, primarily rely on anaerobic metabolism and tire out a lot quicker. Both these subtypes can adapt to changing demands due to exercise and conditioning, highlighting the plasticity that is a key characteristic of these versatile muscle cells." https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/fast-muscle-fiber|DOI:10.3389/fcell.2018.00125|DOI:10.1152/japplphysiol.00636.2019|DOI:10.4161/org.4.3.6312 +262 CL:0000187 CL_0000187 "Muscle cells, also known as myocytes, are specialized cells that are integral to the movement and function of the body. They are characterized by their ability to contract, which brings about motion and force in the organism - this could mean anything from the palpable, voluntary movement through skeletal muscles, to the involuntary pumping of the heart using cardiac muscle cells, or the transportation of substances through the body via the smooth muscles. + +There are three major types of muscle cells in the body: skeletal, cardiac, and smooth muscle cells. Skeletal muscle cells are generally elongated, and because they are attached to the skeleton, they control voluntary movement. Cardiac muscle cells, found only in the heart, are also elongated, but are branched and connected with each other using structures called intercalated disks. These connections allow the cells to contract in a coordinated, rhythmic manner, which enables the constant heartbeat. Lastly, smooth muscle cells are found in the walls of hollow structures like blood vessels and the digestive tract. They control involuntary movement like the contractions necessary for digestion. + +The functionality of muscle cells lies in their special proteins, mainly actin and myosin, that interact to produce contractions. When energy from ATP (adenosine triphosphate) is used, these proteins slide past one another, shortening the muscle cell and causing contraction. This complex process, which also depends on calcium ions, is known as the sliding filament theory of muscle contraction. Regardless of their type, muscle cells are crucial to the overall function and wellness of an organism, facilitating movement and the operation of various systems." https://www.ncbi.nlm.nih.gov/books/NBK544225|https://www.ncbi.nlm.nih.gov/books/NBK532258/|DOI:10.1101/cshperspect.a023200|https://www.ncbi.nlm.nih.gov/books/NBK559006/ +263 CL:0000189 CL_0000189 "Slow muscle cells, as the name implies, are a type of muscle cell well known for their slow contractile speed. They are also referred to as type I, slow-twitch, or red muscles because of their high myoglobin content which gives them a dark, reddish appearance. These cells are predominantly found in the postural muscles of the body, such as those in the back and lower limbs. + +A defining characteristic of slow muscle cells is their significant resistance to fatigue. This is largely due to their efficient oxidative metabolism, which allows them to continuously contract over extended periods without succumbing to fatigue. This extraordinary endurance is facilitated by a high concentration of mitochondria, which enables the efficient use of oxygen for energy production, and capillaries, which supplies the necessary oxygen and nutrients. Additionally, these cells have an abundant supply of myoglobin, a protein that stores and transports oxygen within the muscle cell, further supporting their aerobic metabolism. + +The primary role of slow muscle cells in the human body is to provide sustained, low-intensity contractions over a prolonged period. They are responsible for maintaining posture and providing stability, rather than delivering short, powerful bursts of activity. They play a pivotal role in supporting various physical activities such as standing, walking, or any form of exercise that requires endurance over speed. " https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/slow-muscle-fiber|DOI:10.1186/s13578-015-0054-6|DOI:10.1093/ptj/81.11.1810|DOI:10.3389/fphys.2021.747214 +264 CL:0000192 CL_0000192 "Smooth muscle cells are a specialized type of muscle cells that are primarily found within the walls of hollow organs such as the intestine, stomach, bladder, uterus, and blood vessels. These cells are an essential component of the autonomic nervous system controling involuntary movements within the body. + +Smooth muscle cells play a vital role in many physiological processes due to their unique functionality. They can contract and relax in a slow, sustained, and controlled manner to help modulate the size and shape of the lumens of the organs they surround. For example, in the digestive system, coordinated contraction and relaxation of smooth muscle cells propels food along the gastrointestinal tract - a process known as peristalsis. In the blood vessels, the smooth muscle cells, by contracting or relaxing, either constrict or dilate the vessels, which in turn, help regulate blood flow and pressure. + +On a cellular level, smooth muscle cells possess a single, centrally located nucleus and contain an arranged network of actin and myosin filaments, which are the proteins responsible for muscle contraction. Unlike their counterparts in skeletal or cardiac muscles, these cells lack specific contact points for these filaments, hence the lack of visible striations. Furthermore, the contraction of smooth muscle cells is regulated by hormones and neurotransmitters, such as acetylcholine and norepinephrine, adding an additional layer of complex regulation to these highly specialized cells." DOI:10.1093/ptj/81.11.1810|https://www.ncbi.nlm.nih.gov/books/NBK556137/|https://www.ncbi.nlm.nih.gov/books/NBK526125|https://www.ncbi.nlm.nih.gov/books/NBK10854/|https://training.seer.cancer.gov/anatomy/muscular/types.html +265 CL:0000358 CL_0000358 "Smooth muscle cells, as a broader category, are non-striated, involuntary muscle cells that usually exhibit contractions and dilation to facilitate numerous physiological functions. Sphincter associated smooth muscle cells are a specific type of smooth muscle cell that are primarily associated with the functioning of various anatomical sphincters in the human body. + +The traits that distinguishes sphincter associated smooth muscle cells from other smooth muscle cells are their location and specialized function in sphincter mechanisms. Sphincter associated smooth muscle cells play a pivotal role in regulating the opening and closure of the bodily sphincters. These sphincters can be found at multiple locations within the body including the gastrointestinal tract (namely the esophagus, stomach, small intestine, and rectum), the urinary tract, and the circulatory system. Upon receiving signals from the autonomous nervous system, these cells contract or relax to modulate the aperture of sphincters, thus controlling the movement of substances through them. Due to their precise and vital functional role, any dysfunction or dysregulation in these cells can lead to serious medical conditions, such as gastroesophageal reflux or urinary incontinence." https://www.ncbi.nlm.nih.gov/books/NBK532857/|https://www.ncbi.nlm.nih.gov/books/NBK482438/|https://www.ncbi.nlm.nih.gov/books/NBK557452/ +266 CL:0000359 CL_0000359 "Vascular associated smooth muscle cells (VSMCs) are specialized cells that constitute a major component of the blood vessel wall in the circulatory system. They derive their name from the predominantly smooth appearance under microscopic examination, as opposed to the striated appearance of cardiac and skeletal muscles. + +A principal function of VSMCs is to regulate vascular tone, which directly dictates blood pressure and blood flow distribution across various body parts. This is achieved through coordinated contraction and relaxation of the muscles in response to a variety of extracellular signals. When a blood vessel is exposed to stimuli like pressure or injury, VSMCs contract, resulting in vasoconstriction and ultimately, an increase in blood pressure. Conversely, in response to vasodilators, these cells relax, leading to vasodilation and a consequent decrease in blood pressure. + +VSMCs are also involved in vascular remodeling, a process where blood vessels adapt their structure to long-term changes in hemodynamic conditions or disease states. In diseases like atherosclerosis and hypertension, an aberrant proliferative and synthetic phenotype of VSMCs contributes to the formation of plaques, leading to vessel hardening or even occlusion. Recent research has further implicated these cells in immune responses, recognizing their function in leukocyte recruitment and inflammation, factors that are largely instrumental in vascular pathologies." DOI:10.3390/ijms20225694|DOI:10.1093/cvr/cvs135|DOI:10.1093/cvr/cvy023|DOI:10.1161/ATVBAHA.118.311229|DOI:10.3389/fimmu.2020.599415 +267 CL:0002098 CL_0002098 "Cardiac myocytes, also known as cardiac muscle cells, form the majority of the cardiac tissue and are responsible for the contractile function of the heart. These myocytes are columnar-shaped cells with centrally located nuclei, and they exhibit visibly striated cytoplasm due to the organized array of myofibrils, which are composed of filaments of actin and myosin. Cardiac myocytes connect with each other through specialized structures called intercalated discs, facilitating electrical and mechanical continuity and enabling synchronous contraction of the heart. They also possess a high number of mitochondria to meet their high energy demand for continuous heartbeat action. + +Cardiac myocytes are capable of automaticity, meaning they have the unique ability to spontaneously and rhythmically generate their electrical impulses, a characteristic led by pacemaker cells. The electrical signals initiated and propagated in these cells are responsible for heartbeats. They also respond to the electrical signals transmitted by the autonomic nervous system and chemical signals like hormones. Thus, cardiac myocytes not only participate in maintaining the heart’s function but also play a role in modulating heart rate and strength of contraction in response to the body's changing needs. Consequently, malfunction of these cells leads to serious cardiac diseases such as heart failure and arrhythmias." https://www.ncbi.nlm.nih.gov/books/NBK572070|https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/cardiac-muscle|DOI:10.3389/fphys.2013.00102|https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164530 +268 CL:0002131 CL_0002131 "The ventricular cardiac myocyte is a specialized cell type found in the cardiac tissue. Specifically, these cells are located in the ventricles of the heart, which are the bottom chambers responsible for pumping blood out of the heart to the lungs and the rest of the body. + +The primary function of the cardiac myocyte is to support the rhythmic contraction and relaxation of the heart. This function is facilitated by many specialized structures within the cells. These cells are highly rich in mitochondria, which provide the energy supply necessary for the repetitively forceful contractions of the heart. Moreover, these cells are connected by intercalated discs which support synchronized contraction. Cardiac myocytes also exhibit a phenomenon referred to as automaticity or autorhythmicity, which enables them to spontaneously depolarize and fire action potentials without neural input. + +Additionally, the cardiac myocyte also contributes to the conduction system of the heart. They transmit the electrical impulses that are generated in the sinoatrial node (the natural pacemaker), through the ventricles, leading to coordinated contraction and efficient pumping of blood. It is the orchestrated sequence of ventricular myocyte contraction and relaxation that enables the heart to serve as an effective pump, ensuring oxygenated blood is delivered to different parts of the body. Therefore, the function of the heart, in its capacity as a pump and conduction system, is highly dependent on these specialized cells, making them absolutely integral to cardiovascular function." https://www.ncbi.nlm.nih.gov/books/NBK545195/|DOI:10.1016/j.ccep.2010.10.012|https://www.sciencedirect.com/topics/medicine-and-dentistry/electrical-conduction-system-of-the-heart +269 CL:0002129 CL_0002129 "Regular atrial cardiac myocytes, also known as atrial myocytes, are specialized muscle cells found in the atria – the upper chambers of the heart. They contract and relax during the heart's cycle, modulating the pumping of blood through the atria and into the ventricles. Additionally, endowed with inherent rhythmic electrical activity, atrial myocytes contribute significantly to the initiation and propagation of the heart’s electrical impulses. + +A distinguishing feature that separates atrial myocytes from other cardiac myocytes is their ability to synthesize and secrete atrial natriuretic peptide (ANP) in response to atrial stretch or dilatation. ANP acts as a potent vasodilator and diuretic, helping to maintain blood pressure and volume homeostasis. The phenomena of atrial stretch or distension, which triggers ANP release, is often in response to excess blood volume entering the heart, providing a mechanism at the cellular level which actively regulates systemic cardiovascular balance. + +Like all cardiac myocytes, atrial myocytes are embedded in a dense network of connective tissue that provides structural support. These cells are characterized by a single, centrally located nucleus, and overall, have a rod-like appearance with branching ends that connect with adjacent cells to form a continuous, synchronized ensemble. Their cytoplasm is abundant with mitochondria, reflecting the high energy demand associated with constant contraction and relaxation. At the ultrastructural level, atrial myocytes display striations due to the regular arrangement of actin and myosin proteins, which facilitate the contraction process essential for the heart's pump function." DOI:10.1016/j.bbamcr.2015.11.025|DOI:10.1111/pace.14107|https://www.sciencedirect.com/topics/neuroscience/cardiac-action-potential|DOI:10.1172/JCI25417|https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/cardiac-muscle +270 CL:0000746 CL_0000746 "Cardiac muscle cells, also known as cardiomyocytes or cardiac myocytes, are specialized cells that form the heart tissue. These cells are elongated, branched, and contain a single centrally located nucleus. Their anatomy is composed primarily of densely packed myofibrils, which are protein structures that consist of sarcomeres - the fundamental units of muscle contraction. Cardiac muscle cells are united at their ends through specialized junctions known as intercalated discs, which allow the heart to contract in a unified, powerful and rhythmic way. + +Functionally, cardiac muscle cells are responsible for the heart's consistent pumping action that circulates blood throughout the body. Unlike most cells in the body, cardiac muscle cells spontaneously depolarize and generate action potentials without external stimulation. This unique trait stems from the presence of ion channels in the cells' membrane that allow a cyclic flow of ions across the membrane, which create the electrical impulses necessary for heart contraction. The spread of these electrical signals from one cardiac muscle cell to another - facilitated by the interconnected network made by the intercalated disks - results in a synchronized contraction of the heart muscle. + +Unlike skeletal muscle cells which can tire and need rest, cardiac muscle cells have to work ceaselessly throughout the entire lifespan, without the opportunity for rest, to ensure continuous circulation of blood. This is made possible through the high volume of mitochondria and a constant supply of oxygen from coronary circulation. In conclusion, cardiac muscle cells, through their unique structure and vital functionality, play a pivotal role in sustaining life by providing the means for blood to reach every cell in the body." https://www.ncbi.nlm.nih.gov/books/NBK572070|DOI:10.1016/j.ccep.2010.10.012|DOI:10.1038/nrcardio.2016.203|https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/cardiac-muscle|DOI:10.1016/j.ccep.2010.10.012 +271 CL:0002366 CL_0002366 "Myometrial cells are specialized smooth muscle cells located in the myometrium, the middle layer of the uterine wall. Unique to female reproductive physiology, they play a key role in pregnancy and childbirth. + +These cells are distinctive in their capability to substantially increase in size and number during pregnancy, preparing the uterus to accommodate the growing fetus. As pregnancy progresses, myometrial cells demonstrate a progressive growth in uterine mass through cellular hypertrophy. They are also responsible for the production of extracellular matrix proteins like collagen, which aids in supporting cell structure and function, further facilitating uterine enlargement. + +During childbirth, myometrial cells are responsible for the expansion and contraction of the uterus. They can propagate action potentials and generate considerable force, which is critical to their function in the reproductive system. After pregnancy, these cells can reduce in size, a process known as uterine involution. Given the important role these cells play in female reproductive physiology, dysregulation of the myometrial cell function can contribute to uterine pathologies such as uterine fibroids. +" https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/myometrium|DOI:10.1073/pnas.070447210|DOI:10.1177/1535370220938741|https://www.sciencedirect.com/topics/medicine-and-dentistry/uterine-contraction|DOI:10.1093/humupd/dmr031 +272 CL:0002372 CL_0002372 "Myotubes are multinucleated cells and are categorized under the umbrella of skeletal muscle cells. They are formed through an intricate process known as myogenesis, which is a part of skeletal muscle development. It is vital to note that myotubes are not terminally differentiated but are precursors to mature muscle fiber cells. + +Myotubes come to life through the fusion of myoblasts, which are undifferentiated mononucleated progenitor cells. In the early stages of embryonic muscle development, myoblasts proliferate rapidly under the influence of growth and differentiation factors. As myoblasts reach confluence, they withdraw from the cell cycle, align themselves with each other, increase expression of muscle-specific proteins, and ultimately fuse to form myotubes. The formation of myotubes heralds a critical transition, as this is when cells shift from proliferation and growth to differentiation and maturation. + +Functionally, myotubes play a critical role in the formation and development of skeletal muscles. Myotubes gradually grow in size through the incorporation of additional myoblasts and eventually mature into muscle fibers, the contractile units of skeletal muscles. During this maturation process, myotubes polymerize their soluble muscle-specific proteins into myofibrils, which are essential for muscle contraction. Overall, myotubes are vital players in the complex process of muscle development and homeostasis." DOI:10.1007/s10544-012-9709-9|https://www.sciencedirect.com/topics/medicine-and-dentistry/myotube|https://www.ncbi.nlm.nih.gov/books/NBK10006 +273 CL:0002504 CL_0002504 "Enteric smooth muscle cells are a specialized type of cell found in the gastrointestinal tract. They are an integral part of the enteric nervous system, which regulates the functions of the gastrointestinal system. These cells have a unique structural organization that enables their primary function: the contraction and relaxation necessary for the propulsion of gastrointestinal contents. + +Smooth muscle cells in the enteric system possess unique attributes that distinguish them from other smooth muscle cells in the body. One crucial function is peristalsis, where these cells contract in a coordinated manner, generating a wave of contraction and relaxation. This peristaltic movement facilitates the movement of food particles through the digestive tract, playing a vital role in the digestion and absorption processes in animals. Additionally, these cells are responsible for maintaining the tone of gastrointestinal sphincters, controlling passage and preventing one-sided movement of the contents. + +Enteric smooth muscle cells are also involved in local immune responses of the gastrointestinal tract. They can communicate with local immune cells and secrete cytokines or other signaling molecules in response to infectious organisms, which makes them crucial mediocellular players in gastrointestinal homeostasis and response to disease. Their interactions with other cell types, such as neurons, myofibroblasts, and interstitial cells of Cajal, further contribute to these cells' role in maintaining the physiological functions of the gastrointestinal system. Overall, enteric smooth muscle cells provide an indispensable contribution to the complex operations of the digestive tract." DOI:10.1038/nrgastro.2012.168|DOI:10.1371/journal.pcbi.1009644|DOI:10.1111/j.1365-2982.2012.01986.x +274 CL:0002539 CL_0002539 "Aortic smooth muscle cells are specialized and highly differentiated muscle cells that are located in the tunica media layer of the aorta. They consist of spindle-shaped cells with a centrally located nucleus. These cells are rich in actin and myosin, muscle contractile proteins, that allow them to exert force and change shape. + +Aortic smooth muscle cells play a vital role in maintaining blood pressure and circulation, and are essential for vascular integrity and function. The primary function of these cells is contraction and relaxation, which enables the regulation of blood flow and pressure in the aorta, and helps in the distribution of oxygen and nutrients throughout the body. + +Additionally, a critical characteristic of smooth muscle cells is their plasticity. They can undergo phenotypic modulation in response to changes in their environment or vascular injury, switching from a contractile to a synthetic phenotype. The contractile phenotype is characterized by high contractility and low proliferation rate, while the synthetic phenotype is marked by increased cell proliferation and matrix synthesis but reduced contractile function. + +Aortic smooth muscle cells have a significant role in the physiological and pathological processes of the cardiovascular system. In the normal physiological state, they contribute to the elasticity and flexibility of the aorta. Conversely, in pathological states, changes in the function and structure of aortic smooth muscle cells are connected with various vascular diseases, including atherosclerosis, hypertension, and aneurysm. " https://www.sciencedirect.com/topics/medicine-and-dentistry/aortic-smooth-muscle-cell|DOI:10.7150/ijbs.49871|https://training.seer.cancer.gov/anatomy/cells_tissues_membranes/tissues/muscle.html|DOI:10.1016/j.devcel.2005.05.017|DOI:10.1111/febs.12414 +275 CL:0002591 CL_0002591 "Smooth muscle cells of the pulmonary artery form a principal component of the pulmonary artery's media layer, the middle section of the artery wall typically found between endothelial inner layer (intima) and the outermost connective tissue layer (adventitia). The unique structure of these cells, defined by fusiform shape and the absence of striations, sets them apart from other muscle cell types, including cardiac and skeletal. + +The primary function of smooth muscle cells of the pulmonary artery is to regulate the diameter of the pulmonary artery, which in turn controls the flow of blood into the lungs. They accomplish this task through the contraction and relaxation, indicative of vasoconstriction and vasodilation respectively. When these cells contract, the diameter of the artery narrows, leading to reduced blood flow. Conversely, relaxation of these cells widens the artery, facilitating increased blood flow. Such blood flow modulation is crucial for the maintenance of blood pressure and ensuring that the lungs receive an adequate blood supply for efficient oxygen exchange. + +As a result, abnormal function or proliferation of these cells can contribute to conditions such as pulmonary hypertension, a condition characterized by high blood pressure in the arteries leading to the lungs. This can occur due to hypoxia (lack of enough oxygen), leading to excessive constriction or proliferation of the smooth muscle cells. " DOI:10.1016/j.apsb.2012.12.007|DOI:10.1124/pr.115.010652|https://www.sciencedirect.com/topics/medicine-and-dentistry/pulmonary-artery-smooth-muscle-cell +276 CL:0002598 CL_0002598 "Bronchial smooth muscle cells are specialized types of cells found in the bronchi of the respiratory system in mammals. These bronchi are tubular structures that function to carry air from the trachea into the lungs. As part of the smooth muscle tissue, bronchial smooth muscle cells are involuntary cells, meaning they function with minimal direct voluntary control. They are characterized by their elongated spindle-shaped structure, with each cell containing a single central nucleus. + +The primary function of bronchial smooth muscle cells is to control airway diameter, which directly influences the flow of air into and out of the lungs. Muscular contractions and relaxations mediated by these cells enable the bronchi to constrict or expand, facilitating the regulation of respiratory airflow. Additionally, these cells play a pivotal role in immune responses as they produce and release various substances that can instigate or lessen inflammation of airway tissue. Furthermore, bronchial smooth muscle cells can proliferate and lay down collagen and other extracellular matrix proteins, contributing to the structural integrity of the bronchial tubes. + +In pathological conditions, such as asthma and chronic obstructive pulmonary disease, the function and biology of bronchial smooth muscle cells change. Asthma, for example, is associated with an abnormal increase in the mass of the bronchial smooth muscles, leading to narrowing of the airways and resultant breathing difficulties. These cells also exhibit altered contractile behavior and an augmented immune response during inflammatory lung diseases." https://www.ncbi.nlm.nih.gov/books/NBK537353/|https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/bronchial-muscle|DOI:10.1183/09031936.00019810|DOI:10.1152/japplphysiol.00313.2006 +277 CL:0002600 CL_0002600 "Smooth muscle cells of the trachea have a characteristic 'smooth' (non-striated) appearance under the microscope, a distinguishing feature that differentiates them from skeletal and cardiac muscle cells. The smooth appearance is due to the organization of actin and myosin filaments in the cell, which allows for a controlled, contractile function. + +These cells play a key role in controlling the diameter of the trachea, thus regulating the airflow. They are responsible for the involuntary constriction and relaxation of the trachea influencing the air passage during various physiological behaviors like breathing, coughing, and sneezing. This autonomic control allows for adaptations to specific body requirements without conscious control, such as increasing air flow during exercise or restricting it during rest. + +In conditions such as asthma, chronic bronchitis, and emphysema, there are changes in smooth muscle cells. For example, the mass of smooth muscle cells increases in chronic airway diseases, possibly in response to chronic inflammation. This increase may indicate a pathological condition or be a part of the body's response to injury and repair." https://www.ncbi.nlm.nih.gov/books/NBK9961|DOI:10.1016/s1357-2725(02)00259-5|https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/airway-smooth-muscle +278 CL:0002601 CL_0002601 "Uterine smooth muscle cells are specialized cells that make up the majority of the uterus and in particular, the myometrium. The myometrium is a thick, involuntary muscle layer, principally consisting of verticillate cell bundles that sculpt the helical architecture of the uterus. This dense muscular tissue, packed with uterine smooth muscle cells, is responsible for the significant contractile force witnessed during the physical processes of labor and childbirth. + +In the non-pregnant uterus, they exist in a quiescent phase. Upon implantation, these cells are primarily responsible for the expansion consequently allowing the uterus to accommodate the growing fetus. Towards the end of pregnancy, under the influence of hormonal and mechanical signals, uterine smooth muscle cells transition from a relaxed phase to an active contractile phase, culminating in the delivery of the fetus. + +At the cellular level, these transitions involve significant changes in the electrophysiological properties of uterine smooth muscle cells. Governed by a complex interplay of ion channels, transporters, and signaling proteins, these cells adjust their electrical activity, conduction properties, and contracting mechanisms. Any issues with these processes can result in problems such as preterm birth or labor dysfunction. + + + + + +" DOI:10.1177/0036850419850431|https://www.ncbi.nlm.nih.gov/books/NBK532927/|DOI:10.3791/56639|DOI:10.1203/00006450-199811000-00001 +279 CL:0002673 CL_0002673 "Tongue muscle cells are responsible for essential functions like mastication, deglutition (swallowing), phonation (speech), and taste receptivity. They can be classified into two functional classes - extrinsic and intrinsic muscle cells. + +The extrinsic tongue muscle cells originate outside the tongue and are primarily involved in determining the position of the tongue within the mouth. Muscle groups such as the genioglossus, hyoglossus, and styloglossus are composed of these extrinsic muscle cells and grant the tongue its wide range of motion. + +The intrinsic tongue muscle cells, on the other hand, originate and function within the tongue itself, influencing the shape of the tongue during speech, eating, and swallowing. These cells can contract to alter the tongue's shape, making it long, short, curled, or flat, as needed. Together, these two types of muscle cells allow the tongue to perform its vital functions effectively. Moreover, they play a critical role in maintaining oral health by facilitating physical cleaning of the oral cavity and assisting in the mechanical breakdown of food." https://www.ncbi.nlm.nih.gov/books/NBK554405/|https://www.ncbi.nlm.nih.gov/books/NBK507782/|DOI:10.1002/ca.21011 +280 CL:0008002 CL_0008002 "Skeletal muscle fibers, or myofibers, are specialized cells responsible for voluntary movements, posture maintenance, and physical strength in the animal body. As striated muscle cells, they exhibit a unique elongated, cylindrical, and multinucleated structure formed through the fusion of myoblasts. + +Two main types, slow-twitch (Type I) and fast-twitch (Type II) fibers, serve different functions—slow-twitch fibers excel in endurance activities, relying on oxidative phosphorylation, while fast-twitch fibers are adept at powerful, brief movements, utilizing glycolytic metabolism. + +The functioning of skeletal muscle fibers relies on myofibrils, composed of sarcomeres, the contraction units containing actin and myosin proteins. The cyclical interaction of these proteins, fueled by ATP, results in muscle contraction, following the sliding filament theory. The sarcolemma, the plasma membrane, facilitates electrical signal propagation for muscle contraction, and the sarcoplasmic reticulum stores calcium, crucial for initiating muscle contraction in response to nervous system signals." https://www.ncbi.nlm.nih.gov/books/NBK537139|DOI:10.3390/ijms24032903|DOI:10.3389/fcell.2018.00125|https://www.ncbi.nlm.nih.gov/books/NBK537139/|DOI:10.3390/biom12040488 +281 CL:1000278 CL_1000278 "The smooth muscle fiber of the ileum primarily refers to a specific class of muscle cells present in the ileum, the final segment of the small intestine. Distinguished from skeletal muscle and cardiac muscle, smooth muscle does not possess striations and is under the control of the involuntary nervous system. + +These cells primarily facilitate the movement of digested food, a process known as peristalsis. These cells coordinate rhythmic contractions and relaxations, propelling the chyme toward the colon. This process is vital for efficient nutrient absorption in the small intestine and the transfer of undigested material to the large intestine. Moreover, the smooth muscle fibers enhance the ileum's ability to expand and adapt to volume changes without elevating internal pressure, known as compliance. + +The smooth muscle fiber of the ileum contributes to reflex responses, enhancing muscle contractions to propel intestinal contents in different physiological conditions. This involves intricate molecular signaling with neurotransmitters, hormones, and local signals. Thus, beyond its structural role, the smooth muscle fiber is crucial for the physiological functions of digestion and absorption in the small intestine. +" https://www.ncbi.nlm.nih.gov/books/NBK532857/|https://www.ncbi.nlm.nih.gov/books/NBK556137/|DOI:10.1152/advan.00025.2003 +282 CL:1000443 CL_1000443 "Ciliary muscle cells are specialized contractile cells that constitute the ciliary muscle, a component of the eye in vertebrates. These cells form a ring around the iris, the eye's colored part. Ciliary muscle cells fall into the category of smooth muscle cells, characterized by their lack of the striations typical of skeletal and cardiac muscle cells. Their shape is elongated and pointed at both ends, and they occur in multi-nucleated syncytia where many cells share the same cytoplasm. + +Ciliary muscle cells primarily control the eye's accommodation, adjusting the thickness and curvature of the lens to fine-tune the focus of light on the retina. When ciliary muscle cells contract, tension on the zonular fibers holding the lens in place is reduced, allowing the lens to become thicker and increase its refractive power. Conversely, when the ciliary muscle cells relax, the tension on the zonular fibers increases, causing the lens to become flatter and decrease its refractive power. This adjustment facilitates clear vision at different distances, ranging from near to far objects. + +Additionally, ciliary muscle cells play a role in draining the eye's aqueous humor, which is the clear fluid that fills the anterior chamber of the eye between the cornea and the lens. By controlling the shape of the surrounding trabecular meshwork through muscle contractions and relaxations, ciliary muscle cells indirectly regulate intraocular pressure, a factor critical for preventing ocular conditions like glaucoma. " https://www.sciencedirect.com/topics/medicine-and-dentistry/ciliary-muscle|DOI:10.1111/j.1444-0938.2008.00260.x|DOI:10.1038/srep31171|DOI:10.1016/S1350-9462(98)00011-1 +283 CL:1000487 CL_1000487 "Smooth muscle cells of the prostate constitute a critical component of the prostatic stroma, enveloping glandular structures to support functions like secretion and fluid expulsion. Like other smooth muscles, smooth muscle cells of the prostate lack the striations characteristic of skeletal and cardiac muscle cell. + +Functionally, they play a crucial role in reproductive and urinary functions. Smooth muscle cells of the prostate contribute to the transport and expulsion of prostatic secretions into the urethra and respond dynamically to signaling molecules such as hormones and neurotransmitters. For instance, under sympathetic nervous stimulation, they contract and apply pressure on the gland's ducts, facilitating the secretion process. + +" DOI:10.1101/cshperspect.a030510|https://www.ncbi.nlm.nih.gov/books/NBK279291|https://www.sciencedirect.com/topics/immunology-and-microbiology/smooth-muscle-cell +284 CL:2000046 CL_2000046 "Ventricular cardiac muscle cells, or cardiomyocytes, are specialized cells found in the ventricular walls of the heart. They exhibit unique features, including centrally located nuclei, robust cytoskeletal structures, high mitochondria content, and intercalated discs, which contribute to their efficient pumping of blood throughout the body. + +The main role of ventricular cardiac muscle cells is to coordinate contractions, enabling the heart to pump blood throughout the body. This is achieved through controlled ion movement across cell membranes, generating rhythmic electrical signals called action potentials. Intercalated discs between these cells aid synchronized contractions by allowing efficient signal spread through gap junctions. The high mitochondrial content ensures a constant energy supply for this ongoing contraction cycle. + +Ventricular cardiac muscle cells contribute not only mechanically but also biochemically by secreting essential hormones like atrial natriuretic peptide and B-type natriuretic peptide for blood pressure regulation and cardiac remodeling. These cells exhibit low turnover under normal conditions, emphasizing their long-term stability, yet have limited regenerative capacity following cardiac injuries. Dysfunction in these cells can result in significant cardiac issues, including heart failure." https://www.ncbi.nlm.nih.gov/books/NBK535355|https://www.ncbi.nlm.nih.gov/books/NBK572070/|DOI:10.1016/j.peptides.2018.05.012|DOI:10.1126/science.aam5894 +285 CL:0002243 CL_0002243 "The smooth muscle cell of sphincter of pupil is a specialized cell type typically found within the eye, more specifically within the sphincter muscle of the iris. + +These cells can constrict and dilate in response to light signals, tightly regulating the amount of light reaching the retina. Contraction narrows the pupil in bright conditions (pupillary constriction), protecting the retina from excessive light. In low light, relaxation allows dilation (pupillary dilation), enhancing visual perception in dim conditions. + +These cells are also innervated by parasympathetic fibers from the oculomotor nerve. Light signals to the Edinger-Westphal nucleus stimulate the release of acetylcholine, contracting the cells. On the contrary, sympathetic stimulation induces relaxation. This precise control plays a crucial role in optimizing visual function, highlighting their essential role in vision biology." https://www.ncbi.nlm.nih.gov/books/NBK532252/|https://www.sciencedirect.com/topics/neuroscience/iris-sphincter-muscle|https://www.ncbi.nlm.nih.gov/books/NBK537180/|https://www.sciencedirect.com/topics/neuroscience/iris-dilator-muscle +286 CL:0019019 CL_0019019 "Tracheobronchial smooth muscle cells are universally located in the tracheobronchial tree and play a critical role in controlling and modulating the size of the airway lumen, thereby contributing significantly to the airflow resistance. + +These cells display both phasic and tonic characteristics, which are vital for airway contractility. Phasic activity manifests as cyclic contraction and relaxation, similar to the behavior seen in gastrointestinal smooth muscle cells, whilst tonic activity resembles vascular smooth muscle cells, maintaining a constant degree of tension. These features enable tracheobronchial smooth muscle cells to constrict the airways in response to various mechanical and chemical stimuli, including allergens, parasympathetic nervous stimulation, changes in gas composition, and cold air, thus protecting the delicate alveoli from potential damage. + +Tracheobronchial smooth muscle cells, beyond their contractile function, actively contribute to airway remodeling in conditions like asthma. Their proliferative and synthetic capabilities lead to smooth muscle hypertrophy, hyperplasia, and the production of extracellular matrix components, collectively causing abnormal airway narrowing." https://www.ncbi.nlm.nih.gov/books/NBK556044/|DOI:10.1007/978-3-540-79090-7_5|DOI:10.1152/japplphysiol.00950.2012 +287 CL:0000188 CL_0000188 "Skeletal muscle cells, or myocytes, are essential for the musculoskeletal system, featuring a striated appearance from tightly packed sarcomeres. These elongated, multi-nucleated cells convert ATP into mechanical energ and are key for voluntary movement and posture. They also are responsible for maintaining body temperature, storing nutrients, and stabilizing joints. + +Skeletal muscle cells organize themselves tightly into bundles to form muscle fibers. Embedded within each of these cells are thousands of myofibrils, which are made up of the contractile proteins, actin (the thin filament), and myosin (the thick filament). Contraction of a skeletal muscle cell occurs when these myofibrils shorten, a process driven by the sliding of actin and myosin filaments over each other in a mechanism famously known as the sliding filament theory. + +Additionally, skeletal muscle cells exhibit a high degree of plasticity, which allows for their adaptation in response to alterations in functional demands or damages. They have an innate regenerative capacity due to the presence of satellite cells—quiescent muscle stem cells that reside within the muscle fibers. Upon muscle injury, these satellite cells become activated, proliferate, and differentiate into new muscle cells, thereby contributing to the repair and growth of injured skeletal muscle. With this, skeletal muscle cells serve not only a pivotal biomechanical function but also possess a great capacity for self-healing and regeneration." https://www.ncbi.nlm.nih.gov/books/NBK537139|DOI:10.1002/cphy.c160033|https://www.ncbi.nlm.nih.gov/books/NBK9961/|DOI:10.3390/biology10101056|https://www.nature.com/scitable/topicpage/the-sliding-filament-theory-of-muscle-contraction-14567666/ +288 CL:0000594 CL_0000594 "Skeletal muscle satellite cells (SMSCs) are a type of adult stem cell that nestles on the outer surface of the myofiber, positioned between the sarcolemma (plasma membrane of the muscle cell) and peripheral basement membrane. + +The primary function of SMSCs lies in their capacity to facilitate the growth and repair of damaged skeletal muscle. Upon muscle injury or trauma, these normally quiescent cells activate, proliferate, and differentiate into myoblasts. These myoblasts subsequently mature and fuse to form myotubes, which ultimately help in the repair and rebuilding of muscle fibers. This response is an integral part of the skeletal muscle's ability to recover from injury and adapt to enhanced or changing physical demands, thereby maintaining and improving muscle function. + +Furthermore, SMSCs also contribute to hypertrophic muscle growth due to resistance exercise and endurance training, with the notable feature of their multi-nucleated nature resulting from the fusion of differentiated myoblasts. The additional nuclei support enhanced protein synthesis, thus allowing the muscle fibers to grow and strengthen in response to exercise. In aging and in diseases, the number or functionality of these cells can decrease, leading to impaired muscle regeneration and progressive muscle weakness." DOI:10.1016/s1357-2725(03)00042-6|DOI:10.1186/s13287-022-02706-5|DOI:10.1369/0022155411426780|DOI:10.22074/cellj.2016.4714|DOI:10.1152/physrev.00061.2017 +289 CL:0008011 CL_0008011 "Skeletal muscle satellite stem cells, commonly known as satellite cells, play a crucial role in muscle repair and regeneration. Originating from the myogenic lineage during embryonic development, these cells remain mostly dormant in adult muscle, positioned between the basement membrane and the sarcolemma. + +The primary function of skeletal muscle satellite stem cells is to support the growth, repair, and regeneration of muscle tissues. In response to muscle injury, they activate, proliferate, and differentiate into muscle fibers, facilitating the rapid healing of damaged tissues caused by strain or injury. Their unique capacity for self-renewal ensures the maintenance of the stem cell pool, while their ability to differentiate enables the formation of specialized cells for muscle repair and regeneration. + +They contribute not only to tissue healing but also to the maintenance of homeostasis and performance in skeletal muscles under normal physiological conditions. The decline in the number and functionality of these cells is associated with age-related loss of skeletal muscle mass and function, known as sarcopenia. +" DOI:10.1016/s1357-2725(03)00042-6|DOI:10.1186/s13287-022-02706-5|DOI:10.1152/physrev.00043.2011|DOI:10.1007/s00018-014-1819-5|DOI:10.1097/BOR.0b013e328358d59b +290 CL:0011027 CL_0011027 "Skeletal muscle fibroblasts (SMFs), with their spindle-shaped morphology, play a crucial role in maintaining the structure and function of skeletal muscles. They produce connective tissues enveloping muscle fibers, offering vital structural support for optimal muscle contraction. SMFs are integral components of the dynamic and complex microenvironment of muscle tissue, contributing significantly to healthy muscle development and homeostasis. + +SMFs primarily synthesize and secrete extracellular matrix (ECM) components, such as collagen, fibronectin, and proteoglycans. The resulting ECM exhibits mechanical properties that resist tensile forces from muscle contractions, ensuring muscle efficiency. It also crucially transmits force during muscle movement, aids muscle attachment to the skeletal structure, and serves as a scaffold for muscle regeneration and repair. + +Following injury, they proliferate and transform into myofibroblasts, aiding wound contraction and depositing new ECM for tissue repair. Additionally, these fibroblasts modulate inflammatory responses by secreting cytokines and interact with other cell types, like immune cells and satellite cells, to coordinate muscle healing. In diseases, an imbalance in SMF activity may lead to conditions such as fibrosis, marked by excessive ECM deposition and impaired muscle function." DOI:10.1016/j.diff.2016.05.007|DOI:10.1186/s13578-021-00579-4|DOI:10.1186/s13578-022-00856-w +291 CL:0000351 CL_0000351 "Trophoblast cells, originating from the blastocyst's outer layer, are highly specialized and pivotal for embryo development. Their crucial roles include facilitating implantation and contributing to the formation of the placenta, an essential organ for fetal nutrition, gas exchange, and waste removal during pregnancy. + +These cells play a crucial role in implantation by adhering to the uterus lining. Post-implantation, some trophoblast cells differentiate, forming syncytiotrophoblasts. These multi-nucleated cells absorb nutrients, release waste, and secrete hormones, including human chorionic gonadotropin (hCG), sustaining pregnancy. + +Trophoblast cells also play a crucial role in immune tolerance, preventing the maternal immune system from treating the fetus as foreign. This balance is vital for a healthy pregnancy. Dysfunctional trophoblast cells may lead to complications like miscarriages or preeclampsia, emphasizing their importance in both embryology and reproductive medicine." https://www.ncbi.nlm.nih.gov/books/NBK53245|DOI:10.1530/JOE-17-0402|DOI:10.1016/j.jri.2023.103811 +292 CL:0000525 CL_0000525 "Syncytiotrophoblasts are a continuous, specialized layer of epithelial cells, covering the entire surface of villous trees and directly interact with maternal blood. + +One primary role of syncytiotrophoblast cells is the active transport of nutrients from the maternal to the embryonic circulation, supporting the nourishment and development of the fetus. These cells express various nutrient transporters, enabling the diffusion of essential substances like glucose and amino acids across the placental barrier. Moreover, syncytiotrophoblasts serve as a key site for producing critical pregnancy hormones, including human chorionic gonadotropin (hCG), progesterone, and estrogen, contributing to the maintenance of pregnancy and preparing the mother's body for lactation. + +Despite being an immunoprivileged site, the syncytiotrophoblast layer acts as the first line of defense against maternal immune rejection. This defense involves the downregulation or absence of classical major histocompatibility complex preventing the mother's immune cells from perceiving the fetus as a foreign body. Additionally, these cells function as a barrier between maternal and fetal blood, facilitating the selective exchange of gases and small molecules while preventing the direct exchange of cells and large molecules. " https://www.ncbi.nlm.nih.gov/books/NBK53245/|DOI:10.3390/nu15163564|DOI:10.1155/2012/179827|DOI:10.1095/biolreprod.114.121798|DOI:10.1155/2022/7567708 +293 CL:0002488 CL_0002488 "Trophoblast giant cells are specialized cells that form during the early stages of mammalian embryonic development. Within the trophoblast cell category, these cells, marked by their large, multinucleated structure, play a pivotal role in the early stages of pregnancy, particularly during embryo implantation and the maintenance of pregnancy. + +Trophoblast giant cells are predominantly located at the fetal-maternal interface, where they aid in establishing the connection between the maternal blood supply and the embryonic circulatory system. This is achieved by the invasion and remodeling of maternal spiral arteries, a process carried out by a subset of these cells known as invasive trophoblast giant cells - a necessary step to ensure sufficient nutrient supply to the growing fetus. Additionally, these cells participate in the immune defense mechanism, secreting immunosuppressive molecules to protect against maternal immune rejection. + +These cells are also the primary sources of progesterone, crucial for maintaining the uterine lining during pregnancy, and placental lactogen, which influences the mother's metabolic state to promote fetal growth. In essence, trophoblast giant cells serve as integral mediators, connecting the developmental needs of the fetus with the adaptive physiological changes in the mother." DOI:10.1172/JCI22991|DOI:10.1007/s00018-019-03104-6|DOI:10.1002/dvdy.10291|DOI:10.3389/fimmu.2021.717884 +294 CL:0008036 CL_0008036 "Extravillous trophoblasts (EVTs), a specialized subset of trophoblast cells, play crucial roles in establishing and sustaining pregnancy. + +Firstly, they anchor the fetus to the maternal tissue, providing structural stability. Secondly, they are instrumental in modifying the maternal spiral arteries to ensure an adequate supply of maternal blood to the placenta and the developing fetus. EVTs invade maternal decidua and myometrium and replace the endothelial lining of the spiral arteries, transforming these high-resistance, narrow vessels into low-resistance, wide vessels, favouring higher blood flow. Thirdly, these cells also play an immunological role, creating an environment conducive to the acceptance of the semi-allogeneic fetus, by expressing non-classical MHC molecules, thereby averting any potential maternal immune response towards fetal tissues. + +While EVTs are commonly associated with healthy pregnancies, abnormalities in their function or development have been connected to problematic pregnancies. Conditions like pre-eclampsia and fetal growth restriction (FGR) may arise if EVT cells do not effectively invade the maternal decidua or adequately remodel. " DOI:10.1080/19336918.2015.1089376|DOI:10.1080/19336918.2015.1120397|DOI:10.1007/s12522-011-0102-9|DOI:10.1016/j.it.2017.01.009|DOI:10.1016/j.preghy.2010.10.003 +295 CL:2000002 CL_2000002 "Decidual cells, originating from the endometrial lining in the uterus, undergo significant transformations during pregnancy and are integral to its preparation and maintenance. Their conversion from endometrial fibroblast to a secretory phenotype, known as decidualization, occurs as a normal process in the menstrual cycle or in response to embryo implantation. + +With crucial roles in regulating maternal immune responses and placental development, decidual cells have a twofold function: preventing rejection of the conceptus by the mother's immune system and guiding placental development to avoid excessive trophoblast invasion leading to pre-eclampsia. During decidualization, these cells secrete proteins and growth factors supporting embryo implantation and sustaining early pregnancy. Furthermore, decidual cells modulate the activities of natural killer cells, macrophages, and T cells in the uterus, maintaining a balance of pro-inflammatory and anti-inflammatory conditions during pregnancy. " DOI:10.3390/ijms21114092|DOI:10.1002/rmb2.12088|DOI:10.1093/humupd/dmw004|DOI:10.1111/j.1749-6632.2010.05938.x +296 CL:2000060 CL_2000060 "The placental villous trophoblast, a highly specialized cell type crucial for placental development, plays a key role in facilitating exchanges between the maternal bloodstream and the developing fetus. + +Structurally, placental villous trophoblasts are situated on the villous tree structures, forming an outer epithelial layer. Comprising two subtypes—proliferating cytotrophoblasts forming the inner layer and terminally differentiated syncytiotrophoblasts constituting the outer layer in contact with maternal blood—these cells define the placental architecture. + +Functionally, placental villous trophoblasts play pivotal roles in forming and maintaining the placenta, ensuring the safe development of the fetus. Their primary function involves managing substance exchange between the mother and fetus, mediating the transfer of gases, nutrients, hormones, and waste materials to support optimal fetal growth. Additionally, these trophoblasts synthesize and release crucial hormones like human chorionic gonadotropin (hCG), which maintains the decidua and signals the mother's body to sustain pregnancy. Acting as a physical and immunological barrier, they protect the fetus from maternal immune cells and prevent the transmission of pathogens, contributing significantly to the success of pregnancy." DOI:10.3390/nu15163564|DOI:10.1007/s00018-019-03104-6|DOI:10.3389/fimmu.2020.00343 +297 CL:0011101 CL_0011101 "The chorionic trophoblast cell, vital for placental development in mammals, originates from the blastocyst's outer layer, the trophectoderm. As a significant component of the placenta, the chorion forms the external fetal-maternal interface and consists primarily of chorionic trophoblast cells. These cells are pivotal in embryogenesis, fetal nutrition, waste removal, and immune response generation, contributing crucially to the success of pregnancy. + +Chorionic trophoblast cells undergo trophoblast differentiation, giving rise to specialized sub-types: cytotrophoblasts and syncytiotrophoblasts. Cytotrophoblasts, found in the inner layer, serve as stem cells and contribute to proliferative activities. In contrast, syncytiotrophoblasts, originating from cytotrophoblasts, form the outer layer with a distinctive multinucleated, continuous, and non-proliferative structure. These cells play a key role in maternal-fetal gas and nutrient exchange, producing essential hormones like human chorionic gonadotropin (hCG), progesterone, and estrogen, vital for sustaining pregnancy. + +Apart from their physiological roles, chorionic trophoblast cells play a crucial role in shielding the fetus from the maternal immune system. They accomplish this by modifying the expression of major histocompatibility complex (MHC) molecules, which are self-identifying proteins utilized by the immune system to identify foreign cells. Through selective expression of specific types of these molecules, trophoblast cells can evade cytotoxic T cells that might otherwise attack them, while still retaining the ability to attract natural killer cells. These natural killer cells assist in trophoblast invasion and the remodeling of blood vessels in the uterus." DOI:10.1007/s00018-019-03104-6|DOI:10.1093/biolre/ioy070|https://www.sciencedirect.com/topics/medicine-and-dentistry/placenta-development|https://www.ncbi.nlm.nih.gov/books/NBK53245/|DOI:10.1155/2014/579279 +298 CL:0000056 CL_0000056 "Myoblasts are characterized as stem cells that harbor precursors of skeletal muscle cells. They originate from the mesoderm during embryogenesis and express specific protein markers like MyoD or myf-5. Characterized by their ability to proliferate, differentiate, and form syncytia known as myotubes, myoblasts play a central role in muscle development and regeneration. + +Upon receiving specific biochemical signals, myoblasts undergo intricate transcriptional and morphological changes, differentiating into mature muscle cells. Besides their crucial role in embryonic development, myoblasts also exist as resident adult stem cells in skeletal muscle tissue known as satellite cells. These satellite cells remain quiescent until triggered by muscle injury or stress, at which point they re-enter the cell cycle, undergo proliferation, and differentiate to facilitate the repair of damaged muscle tissue. + +" DOI:10.3727/000000006783981710|DOI:10.1016/0092-8674(93)90621-V|DOI:10.1016/j.semcdb.2017.11.011|https://www.sciencedirect.com/topics/engineering/myoblasts +299 CL:0000513 CL_0000513 "Cardiac muscle myoblasts play a vital role in the development of the heart muscle, particularly in the ventricular and atrial myocardium. Originating from cardiac progenitor cells, they exhibit an elongated morphology and express specific transcription factors and proteins like Nkx2.5, Gata4, and Mef2c. + +The primary function of cardiac muscle myoblasts is to participate in myogenesis. Responding to regulatory signals, these myoblasts undergo proliferation, alignment, and fusion, giving rise to multinucleated, striated myotubes. These myotubes then differentiate into functional cardiomyocytes, forming the muscular walls of the heart. +" DOI:10.3390/cells8121536|https://www.sciencedirect.com/topics/neuroscience/myoblast|https://www.sciencedirect.com/topics/medicine-and-dentistry/cardiac-myoblast +300 CL:0000514 CL_0000514 "A precursor to the smooth muscle cell, the smooth muscle myoblast, is integral to various body systems, including the cardiovascular, gastrointestinal, and respiratory systems. Smooth muscle myoblasts arise from the differentiation of mesenchymal stem cells, a process tightly regulated by specific genetic factors and environmental signals. Their role extends to myogenesis, particularly in the formation of muscular tissue, especially during embryonic development. + +Smooth muscle myoblasts possess distinctive cellular characteristics. In contrast to skeletal muscle myoblasts, they do not fuse to create multinucleated fibers. Instead, they differentiate into individual, uninucleated smooth muscle cells. This differentiation unfolds in two distinct phases: proliferation, marked by rapid division to increase cell numbers, and differentiation, involving structural and functional transformation into mature smooth muscle cells. This intricate process is intricately mediated by various signaling molecules and transcription factors. + +Functionally, smooth muscle myoblasts and the mature muscle cells they generate play pivotal roles in various physiological processes. Smooth muscle cells orchestrate involuntary muscle responses and are integral to body systems that regulate blood flow, propel food along the digestive tract, and control airflow in the respiratory tract. These diverse functions underscore the significance of smooth muscle myoblasts in the body's growth, maintenance, and overall function. " DOI:10.1074/jbc.RA118.001739|https://www.ncbi.nlm.nih.gov/books/NBK544225/|https://www.sciencedirect.com/topics/medicine-and-dentistry/smooth-muscle +301 CL:0000680 CL_0000680 "Muscle precursor cells, commonly referred to as myogenic progenitor cells or myoblasts, play a pivotal role in the intricate processes of muscle regeneration and development. As undifferentiated cells, they harbor the potential to evolve into distinct specialized cells, specifically the muscle cell or myocyte. Their crucial contribution lies in guiding the transformation of the mesodermal layer, one of the three primary germ cell layers in the early embryo, into fully developed skeletal muscle tissues during embryonic development. + +Muscle precursor cells are characterized by their proliferative capacity and rapid differentiation into mature myocytes. They fuse into myotubes, culminating in the formation of muscle fibers. Their responsiveness to signals such as insulin-like growth factors, transforming growth factor-β, and neural inputs enables precise control over their proliferation and differentiation. This regenerative capacity equips them with the ability to repair injured or damaged muscle tissue, a critical function in preserving muscle homeostasis and overall function. These cells also actively contribute to adaptive responses, such as muscle growth and strengthening, in reaction to factors like training or aging." https://www.sciencedirect.com/topics/engineering/muscle-precursor-cell|DOI:10.1089/ars.2007.1792|DOI:10.1152/physrev.00061.2017 +302 CL:0000035 CL_0000035 "Single fate stem cells, or unipotent stem cells, constitute a distinctive subtype among the diverse range of stem cells, exhibiting significant biological roles and applications. These cells possess the inherent ability to self-renew and generate a single, specialized cell lineage exclusive to their nature, reflecting their unipotent or single fate characteristic. Engaged in the maintenance and regeneration of specific tissues or organs, these stem cells play a crucial role as pivotal contributors to the body's self-maintenance and repair mechanisms. + +Single fate stem cells play a crucial role in the body's diverse tissues by ensuring the appropriate renewal and repair mechanisms specific to their respective tissues. For example, the human skin, where basal cells located at the base layer of the epidermis act as single fate stem cells. These basal cells continuously generate new keratinocytes, replacing the older ones shed from the skin surface. This perpetual cycle of renewal exemplifies the fundamental function of single fate stem cells—specialized cellular regeneration to uphold tissue homeostasis and function." https://www.sciencedirect.com/topics/immunology-and-microbiology/stem-cell|DOI:10.52965/001c.37498|DOI:10.1016/j.cps.2017.02.020|https://training.seer.cancer.gov/melanoma/anatomy/layers.html +303 CL:0000037 CL_0000037 "Hematopoietic stem cells (HSCs) are multipotent cells, capable of differentiating into a wide variety of specialized blood cells. During embryonic development hematopoietic stem cells emerge from the hemogenic endothelium, a specialized subset of endothelial cells with hematopoietic potential. HSCs can be found in several organs, in particular in bone marrow, as well as peripheral blood and umbilical cord blood. + +These stem cells have a distinctive ability to self-renew, and to differentiate into all lymphoid and myeloid cell types that together form the blood and immune systems including erythrocytes (red blood cells), leukocytes (white blood cells), and platelets. Their primary function is to ensure the continuous replenishment of the blood and immune system throughout an individual's lifespan. + +In response to various signals, hematopoietic stem cells can either remain dormant or actively divide and differentiate. Under normal conditions, the majority of these stem cells exist in a quiescent (inactive) state, making them somewhat resistant to chemotherapy or radiation therapy in the treatment of various diseases such as leukemia. However, when the body encounters stress such as infection, bleeding, or disease, hematopoietic stem cells can rapidly become active in order to replenish the affected cells and maintain homeostasis. + +Furthermore, hematopoietic stem cells are extremely important in the field of regenerative medicine and transplantation. Regarded as lifesaving in the field of oncology, they are often extracted, purified, and reinfused back into the same (autologous transplantation) or different (allogeneic transplantation) individuals to reestablish a healthy, functioning hematopoietic and immune system after high-dose chemotherapy or to replace dysfunctional bone marrow. Understanding and manipulating the behavior of these stem cells has immense potential in treating various blood disorders, autoimmune diseases, and cancers. +" DOI:10.1038/s41580-019-0103-9|DOI:10.3389/fcell.2022.664261|DOI:10.1101/gr.192237.115|DOI:10.1186/s12915-021-00955-z +304 CL:0000036 CL_0000036 "Epithelial fate stem cells, also known as epithelial stem cells, possess remarkable abilities for self-renewal and the generation of diverse cell types constituting epithelial tissues. The epithelium, derived from these cells, acts as the body's frontline defense against external threats and facilitates the exchange of nutrients, gases, and waste materials within the internal environment. + +Epithelial fate stem cells contribute to tissue development, homeostasis, and repair, maintaining the structural and functional stability of epithelial tissues throughout the human body, including the skin, organs, and glands. Through a delicate balance of quiescence, proliferation, and differentiation, these cells ensure the continuous turnover of epithelial cells. + +Furthermore, these cells serve a critical role in cellular differentiation, where initially unspecialized stem cells mature into specialized entities that perpetuate the functionality of epithelial tissues. This process is intricately regulated by a network of gene expression patterns and external signaling cues to guarantee a coordinated and balanced cellular turnover. Hence, epithelial fate stem cells, with their unique attributes of self-renewal and differentiation, are central to the physiological and reparative functions performed by epithelial tissues in the human body. + + + + + + +" DOI:10.1016/j.cell.2007.01.014|DOI:10.1016/j.stem.2020.09.011|DOI:10.1038/nrm2766|DOI:10.1016/j.celrep.2022.111451 +305 CL:0000646 CL_0000646 "Located at the lowest layer of the skin within the epidermis, basal cells reside at the boundary with the dermis. Their strategic position provides them with advantageous access to the blood and nerve supply, making them crucial contributors to skin functionality and overall body homeostasis. + +Basal cells play a central role in generating keratinocytes, the predominant cell type in the skin. Engaged in continuous proliferation, these cells produce daughter cells that progressively move upward to the skin's surface. Along this journey, they undergo differentiation, transforming into keratinocytes. These keratinocytes further mature into corneocytes, forming the outermost, non-living layer of the epidermis and are eventually shed from the skin's surface. + +They also act as sensory ""alarms"", reacting to different environmental factors. For instance, when the skin comes under the influence of harmful UV radiation, basal cells relay this information to the body, triggering defense mechanisms that try to repair damaged DNA in an attempt to prevent mutation. Because of this highly reactive nature, basal cells are susceptible to mutations, with basal cell carcinomas being one common consequence. Basal cells thus play a pivotal role in both skin regeneration and maintaining skin health, forming the frontline in the body's defense mechanisms against external harm. +" https://training.seer.cancer.gov/melanoma/anatomy/layers.html|DOI:10.1159/000513054|https://www.ncbi.nlm.nih.gov/books/NBK482439/ +306 CL:0000723 CL_0000723 "Somatic stem cells, also known as adult stem cells, are undifferentiated cells found throughout the body post-embryonic development. They reside in specialized niches within tissues such as the bone marrow, brain, muscles, skin, and liver. Fundamentally, these cells possess the ability to self-renew, maintaining their numbers, and to generate differentiated cells that replace dying cells and repair damaged tissues. + +The potency of somatic stem cells varies based on their tissue of origin. For instance, hematopoietic stem cells in the bone marrow exhibit multipotency, giving rise to all blood cell types. Conversely, muscle stem cells display unipotency, generating only muscle cells. + +Somatic stem cells respond to environmental signals that regulate their quiescence, activation, and differentiation states. In response to tissue injury, they proliferate and differentiate into specific mature cell types to replace lost or damaged cells. Intricate mechanisms ensure a delicate balance between self-renewal and differentiation, guiding tissue maintenance and repair without risking aberrant cell proliferation leading to tumor formation. + + + + +" DOI:10.1186/s13287-019-1165-5|https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/adult-stem-cell|DOI:10.1159/000345615|DOI:10.15283/ijsc19127|DOI:10.1016/j.stem.2011.10.004 +307 CL:1000428 CL_1000428 "The epidermal stem cell, a critical component of the skin's structure, is essential for maintaining, repairing, and renewing the epidermal layer. Undifferentiated and capable of becoming various cell types within the epidermis, these cells typically remain quiescent, preserving the skin's longevity and regenerative ability. + +The primary role of these stem cells is to replenish the population of keratinocytes, the key protective cells in the epidermis. When stimulated by signals like injury or normal wear, these stem cells activate, divide, and give rise to both new stem cells and differentiated cells. The latter form layers of stratified keratinocytes that make up the skin's protective barrier. + +Beyond skin-related applications, the regenerative potential of epidermal stem cells has garnered interest in medical and cosmetic fields, particularly for treating burns, chronic wounds, and aging skin. Notably, these cells, specialized for skin tissue, might, under controlled conditions, have the potential to form diverse tissues, expanding possibilities in regenerative medicine." DOI:10.1146/annurev.cellbio.22.010305.104357|https://www.ncbi.nlm.nih.gov/books/NBK26865/|https://www.sciencedirect.com/topics/medicine-and-dentistry/epidermal-stem-cell|DOI:10.1186/s13287-019-1312-z|DOI:10.3390/ijms161025476 +308 CL:1000447 CL_1000447 "The epithelial cell in the stratum germinativum of the esophagus, commonly referred to as a basal cell, is a crucial component of the body's mechanism for tissue homeostasis and regeneration. Situated in the deepest layer of the esophageal lining, these cells are pivotal in preserving the integrity of the esophagus, which faces exposure to various physical and chemical irritants like stomach acid, food particles, and pathogens. + +These cells are renowned for their proliferative potential. When the superficial layers of the esophageal epithelium are damaged, these basal cells are triggered to multiply, differentiate, and migrate upwards to restore the integrity and function of the affected tissue. This process, known as regeneration or repair, ensures that the esophageal wall remains continuous and functional, capable of performing its primary task: the conveyance of food and drink from the mouth to the stomach. + +However, it's crucial to recognize that the continuous cycle of damage and repair in the esophageal epithelium, driven by the epithelial cells of the stratum germinativum, can result in pathological conditions like Barrett's esophagus and esophageal cancer. Under certain conditions, these basal cells may deviate from their normal differentiation into squamous cells and instead transform into abnormal cell types, such as intestinal columnar cells, contributing to the development of these diseases. " DOI:10.1016/j.tcb.2018.04.007|DOI:10.1038/nrc2773|DOI:10.1136/gut.2005.089144 +309 CL:0001024 CL_0001024 "CD34+, CD38- hematopoietic stem cells represent a distinct subset within the broader category of hematopoietic stem cells (HSCs), responsible for the formation of blood and immune cells. Characterized by the presence of CD34 antigen and the absence of CD38 antigen, these cells exhibit a primitive state capable of self-renewal and differentiation. + +CD34 cells play various roles, including inhibiting HSC differentiation, expanding HSCs, participating in signaling transduction, and anti-adhesion mechanisms. CD38, characterized as a type II glycoprotein, was initially recognized as a surface differentiation marker for lymphoid cells. The CD38 gene, with 5694 bases, is located on chromosome 4p15 and shares an extensive evolutionary history with CD157. Comprising 300 amino acid residues, the CD38 protein is a multifunctional ectoenzyme involved in synthesizing and hydrolyzing cyclic ADP-ribose (cADPR) from NAD+ to ADP-ribose. These enzymatic reactions play a crucial role in regulating intracellular Ca2+. + +Notably, CD38 has found application as a prognostic marker in leukemia. In clinical settings, CD34+CD38- HSCs play a crucial role in transplantation procedures, regenerating blood and immune systems after treatments like chemotherapy or radiation therapy. Despite their rarity in the bone marrow, requiring precise isolation procedures, these stem cells are highly valuable in stem cell transplantation therapy. + + + + + +" DOI:10.1186/s40364-016-0080-5|DOI:10.1186/2162-3619-1-12|DOI:10.1016/j.leukres.2019.04.004 +310 CL:0000145 CL_0000145 "Professional antigen presenting cells, also known as APCs, are essential orchestrators of adaptive immunity. These cells possess the abilities to capture and process antigens and constitutively express MHC class II molecules to facilitate antigen presentation. These cells are able to deliver the three signals to activate naïve T cells, thereby initiating adaptive immunity. + +Professional APCs include dendritic cells, macrophages, and B cells. Among these, dendritic cells are often considered the predominant APC as they have been demonstrated to activate naïve T cells. Macrophages and B cells also possess antigen-processing machinery and constitutively express MHC class II molecules. Dendritic cells and macrophages obtain antigens via phagocytosis of cells and cell debris, while B cells obtain antigens via the B cell receptor. + +APCs are responsible for stimulating an appropriate immune response. Following antigen presentation (signal 1), they deliver costimulatory signals (signal 2) and secrete mediators such as cytokines (signal 3) that shape the subsequent immune response. APCs can also induce tolerogenic responses to self-antigens. APCs play important roles in diseases such as cancer and autoimmune diseases." DOI:10.1038/nri3754|DOI:10.3389/fimmu.2022.954936|DOI:10.1159/000512729|DOI:10.1159/000512729|DOI:10.1016/B978-0-12-394447-4.30111-0 +311 CL:0000049 CL_0000049 "The common myeloid progenitor (CMP) is a multipotent cell that serves as a crucial intermediary within the overall framework of hematopoietic cell differentiation, which is the process of blood cell production. This part of the hematopoiesis process leads to the formation of myeloid lineage cells, which includes granulocytes (neutrophils, eosinophils, and basophils), monocytes, erythrocytes (red blood cells), and megakaryocytes (platelet-forming cells). + +The primary function of common myeloid progenitors is differentiation and proliferation into various types of mature blood cells, thereby providing a critical contribution to maintaining homeostasis within the body's immune and circulatory systems. Single-cell analyses have shown that the CMP cell population in is heterogeneous with at least two distinct subpopulations, characterized by different cell surface markers and likely already committed to downstream differentiation into either the granulocyte/macrophage lineage or the megakaryocyte/erythrocyte lineage-restricted progenitor. + +The destiny of a CMP is influenced by numerous cytokines and growth factors in its environment that promote differentiation along specific lineages. For example, IL-3 and GM-CSF stimulate the production of eosinophils, which are essential for the body’s defense against allergens and help fight fungal and parasitic infections. + +By being able to differentiate into a wide range of different immune cells, common myeloid progenitors play a crucial role in the body's ability to respond to injuries, infections, and other physiological challenges. +" DOI:10.1111/j.1600-065X.2010.00963.x|DOI:10.1038/ni.3412|DOI:10.1038/35004599|https://www.sciencedirect.com/topics/engineering/myeloid-progenitor-cell|DOI:10.7554/eLife.60939 +312 CL:0000051 CL_0000051 "The common lymphoid progenitor (CLP) arises from the multipotential hematopoietic stem cell in the bone marrow. Hematopoietic stem cells have the unique capability of developing into any type of blood cell depending on the body's requirements. In contrast, common lymphoid progenitors are already committed to the lymphoid lineage but are still oligopotent with the capability to further differentiate into various types of lymphoid cells. + +In mice, cells in the common lymphoid progenitor population in the bone marrow can be identified by their Lin- IL7rα+ c-Kit+ Sca-1+ cell surface phenotype. The IL-7 receptor is first expressed on common lymphoid progenitor cells and distinguishes them from primitive common myeloid progenitors, and IL-7 is thought to play a critical role in the downstream development and homeostasis of immune cells. + +CLPs give rise to B lymphocytes, T lymphocytes, dendritic cells, and natural killer cells, all of which play a crucial and distinct role in immune responses. B and T lymphocytes are responsible for adaptive immunity, allowing the body to recognize and remember specific pathogens to fight them off more effectively in the future. B lymphocytes are responsible for producing antibodies, while T lymphocytes either help regulate immune responses or directly kill infected cells. Natural Killer cells are part of the body’s innate immune response, providing immediate, nonspecific defense against pathogens. They are able to interact with infected or malignant cells and induce controlled cell death, or apoptosis, effectively eliminating the threat to bodily health. Dendritic cells link the innate and adaptive immune systems by presenting antigens to T cells, promoting an adaptive response. + +Thus, common lymphoid progenitors provide the basis for the body's strategic and layered defense against varied and evolving external threats, making them an essential part of the immune system. + +" DOI:10.1182/blood-2009-08-236398|DOI:10.1111/j.1600-065X.2010.00963.x|DOI:10.1016/s0092-8674(00)80453-5|DOI:10.1038/ni.3168|DOI:10.3389/fimmu.2021.747324 +313 CL:0000084 CL_0000084 "T cells, also known as T lymphocytes, are a critical component of the adaptive immune system. These cells derive their name from the organ where they mature, the thymus. T cells contribute to various immune responses, including cell-mediated immunity and the activation of other immune cells. They are involved in detecting and responding to invading pathogens in the body, including viruses and bacteria, as well cancerous cells. + +T cells are uniquely armed with specialized T cell receptors (TCRs) on their cell surfaces that can recognize and bind to specific antigens displayed on the surface of antigen-presenting cells (APCs). Once the TCR binds to the antigen, the T cell becomes activated and performs its specific function. + +There are various phenotypically distinct subsets of T lymphocytes, each with specific functions. Helper T cells (CD4+ T cells) are responsible for coordinating the immune response by activating other immune cells such as B cells and cytotoxic T cells. The population of helper T cells is very diverse and includes Th1 cells, which mediate immunity against intracellular pathogens, Th2 cells which are crucial for humoral immune responses and defense against extracellular parasites, Th17 cells with a specific role in mucosal immunity and protection against extracellular bacteria and fungi. + +Cytotoxic effector T cells, which are characterized by the cell surface expression marker CD8, are equipped to directly attack and kill infected and transformed cells; they do this through secretion of granzymes and perforin, which results in the apoptosis of the target cell. Regulatory T cells (Tregs) are a subgroup of CD4+ T cells which typically express of forkhead box protein P3 (Foxp3). They are immunosuppressive and maintain tolerance to self-antigens and prevent autoimmune diseases by suppressing exaggerated or unnecessary immune responses. + +Memory T cells are a heterogeneous population of T lymphocytes, representing discreet subsets based on phenotype and with distinct roles in immunity. They ‘remember’ past infections and allow for enhanced immune response when an antigen is encountered again. + +Aberrant development and function of T lymphocytes are implicated in a wide range of diseases including autoimmune diseases, immunodeficiencies, and allergic diseases. +" DOI:10.1016/j.jaci.2022.10.011|DOI:10.1111/imcb.12662|DOI:10.1016/j.immuni.2023.02.010|DOI:10.1016/j.it.2023.08.007|DOI:10.1038/s41590-022-01387-9 +314 CL:0000097 CL_0000097 "Mast cells, also known as mastocytes, are a type of innate immune cell. They originate from multipotent hematopoietic progenitor cells within the bone marrow, after which they migrate into nearly all tissues throughout the body. In these tissues, mast cells undergo complete maturation, with the exception of the blood. They are most densely located in the interfaces between the internal and external environments, such as the skin, respiratory system, and gastrointestinal mucosa. + +Mast cells are crucial players against pathogens and serve as first-line defense components. They contain numerous granules rich in histamine and heparin and are known primarily for their role in allergy and anaphylaxis. Upon encountering an allergen, pathogen, or even certain drugs and toxins, mast cells release these mediators via degranulation. Histamine induces vasodilation and vascular permeability, allowing for immune cells to rapidly reach the site of infection, while heparin prevents clotting in these areas to facilitate immune cell recruitment. Mast cells may also selectively secrete mediators without degranulation. + +These cells also play other functions beyond immune defense. They are involved in wound healing processes and maintenance of tissue integrity, angiogenesis, and even regulation of physiological functions in the gut. Consequently, because of their wide-ranging impacts, abnormalities in mast cell function can result in various disorders, including those related to allergies, inflammation, and autoimmune conditions. " DOI:10.1016/j.bbadis.2010.12.014|DOI:10.1146/annurev-immunol-071719-094903|DOI:10.1056/NEJMra1409760|DOI:10.1007/s11894-010-0132-1|DOI:10.1007/s12016-019-08729-w +315 CL:0000038 CL_0000038 "Erythroid progenitor cells play a key role in the hematopoietic system, specifically in the process of erythropoiesis – the production of red blood cells (erythrocytes). Found within the bone marrow, these cells are dedicated precursors to erythrocytes, and ensue in the hematopoietic lineage from multipotent progenitors. They represent a transitional cell type that bridges the gap between the early-stage erythroid precursors and the maturing red blood cell population. + +The earliest committed erythroid progenitor cell is thought to be the burst-forming unit-erythroid (BFU-E) cell, which after several cell divisions gives rise to another erythroid progenitor, the colony-forming unit-erythroid (CFU-E) cell. + +Erythroid progenitor cells are primarily responsible for responding to the demand for new red blood cells during conditions of physiological stress like infection, blood loss, or illness. This responsive behavior is regulated by a glycoprotein hormone known as erythropoietin, which is produced by the kidneys. Erythropoietin interacts with the receptors on the erythroid progenitor cells, prompting them to proliferate and differentiate into erythroblasts. The erythroblasts then further mature, eventually producing new, functional red cells. + +The role of erythroid progenitor cells extends beyond their main function of erythrocyte production, as they also participate in maintaining the balance of iron in the body. Upon erythroid differentiation, they increase their uptake of transferrin-bound iron for hemoglobin synthesis, a vital component of red blood cells which allows them to transport oxygen. A deficiency or excess of erythroid progenitor cells can lead to extensive health issues such as anemia or polycythemia respectively, emphasizing their crucial role in human health. +" DOI:10.1016/j.exphem.2015.10.007|DOI:10.1097/MOH.0000000000000328|DOI:10.3389/fphys.2019.00304|DOI:10.1182/blood-2014-07-588806|DOI:10.1111/bjh.13938 +316 CL:0000050 CL_0000050 "The megakaryocyte-erythroid progenitor (MEP) cell belongs to the multipotent hematopoietic progenitor cells, which can give rise to multiple different cell types. They are found in the bone marrow, the primary organ where new blood cells are generated. MEPs are specially programmed to develop into two distinct blood cell lineages, namely megakaryocytes, which go on to produce platelets for blood clotting, and the erythroid lineage which consists of red blood cells responsible for oxygen transport in the body. + +The MEP cells are the result of a decision-making process within the hematopoietic stem cell population. Hematopoietic stem cell can differentiate into multiple types of progenitor cells, including myeloid progenitor cells. A further subdivision within this myeloid lineage generates the MEP cells. Therefore, these megakaryocyte-erythroid progenitors represent a key juncture between hematopoietic stem cells and mature blood cell types in the myeloid lineage. + +Megakaryocyte-erythroid progenitor cells play a crucial role in the homeostasis of some of the most crucial constituents of blood. The megakaryocytes produced from these bipotent progenitor cells contribute to hemostasis by producing platelets - small anucleated fragments that are pivotal for blood clotting and preventing bleeding. Similarly, the erythroid lineage from MEP cells gives rise to erythrocytes, which harbor hemoglobin, the molecule that transports oxygen from lungs to every nook and corner of the body. An imbalance or malfunction in MEP function thus can significantly impact human health, leading to diseases like thrombocytopenia or anemia. +" DOI:10.1161/ATVBAHA.119.312129|DOI:10.1016/j.celrep.2018.10.084|DOI:10.1002/stem.2834|DOI:10.1097/MOH.0000000000000625|DOI:10.1182/blood-2016-01-693705 +317 CL:0000094 CL_0000094 "Granulocytes constitute an integral part of the immune system and are a type of white blood cell distinguished by their appearance under a light microscope, which reveals small granules in their cytoplasm. These cells respond to infection with degranulation to release toxic mediators and phagocytosis to engulf pathogens. Granulocytes are produced in the bone marrow and are involved in the body's first-line defense mechanisms against infection and injury. There are three primary types of granulocytes: neutrophils, eosinophils, and basophils, each displaying a unique set of granules housing distinct proteins that contribute to the body's immune response. + +Neutrophils are the most abundant granulocyte type and the body's initial responder to bacterial infections. Upon encountering pathogens, neutrophils degranulate, releasing antimicrobial proteins and generating reactive oxygen species. They can also form neutrophil extracellular traps (NETs), which are web-like structures that capture and neutralize bacteria. Eosinophils primarily response to parasitic infections, as their granules contain proteins such as the cationic protein which are toxic to parasites. Basophils, the least common granulocyte type, play a crucial part in mediating allergic responses. Basophils release histamine and other inflammatory molecules stored in their granules, promoting vasodilation and attracting additional immune cells to the affected site. + +In addition to their role as first responders to infection, more recent research seeks to understand the role of granulocytes as antigen-presenting cells and in the orchestration of the adaptive immune response through their interactions with dendritic cells and lymphocytes. Granulocytes also perform necessary homeostatic functions." "DOI:10.1093/med/9780198746690.003.0513 +|https://www.ncbi.nlm.nih.gov/books/NBK563148/|DOI:10.3389/fimmu.2017.01781/full|DOI:10.1189/jlb.4MR0217-048RR|DOI:10.1007/s00018-020-03509-8" +318 CL:0000451 CL_0000451 "Dendritic cells, named for their tree-like extensions called dendrites, are a type of immune cell that form a critical bridge between the innate and adaptive immune systems. They are derived from hematopoietic bone marrow progenitor cells and can be found throughout the body poised as sentinels in locations such as the skin, lungs, or liver, as well as immune organs such as the thymus, lymph nodes, or spleen. They can also be found in an immature state in the blood. Dendritic cells serve as antigen-presenting cells, with a primary function of processing and presenting antigens to T-cells to facilitate an immune response. + +Upon encountering an antigen, dendritic cells engulf the pathogen via phagocytosis and subsequently process the pathogen into antigens. These antigens are then presented on the surface of the dendritic cell in the context of major histocompatibility complex (MHC) molecules. The dendritic cell migrates to the lymph nodes, containing naive T-cells, and presents the antigens to them. This process triggers the activation of cognate T-cells into effector T-cells, which can then recognize and eradicate cells bearing the same antigen. + +Additionally, the dendritic cells can influence the type of immune response the body will mount. They communicate with T-cells through the use of co-stimulatory molecules and cytokines. Depending on the type of co-stimulatory molecules used and the set of cytokines released, dendritic cells can promote the development of a cellular immune response, dominated by cytotoxic T cells effective against intracellular pathogens such as viruses, a humoral response, mediated by B cells and effective against extracellular bacteria and toxins, or a tolerogenic response. Thus, dendritic cells play a pivotal role in immunity, helping the body to effectively combat infections, prevent autoimmune diseases, and maintain tolerance to healthy self-tissues." DOI:10.1016/bs.ircmb.2019.07.004|DOI:10.1111/imm.12888|DOI:10.1146/annurev-immunol-100311-102839|DOI:10.1146/annurev-immunol-061020-053707|DOI:10.1038/nri.2016.116 +319 CL:0000453 CL_0000453 "Langerhans cells (LCs) are immune cells located in the epidermis. Initially thought to be dendritic cells, they are now considered to be specialized tissue-resident macrophages. They originate from embryonic yolk sac macrophages and fetal liver monocytes, are self-renewing, but may also be replaced by other bone-marrow derived cells during inflammation. + +Langerhans cells possess both macrophage- and dendritic cell-like properties and functions. They can self-maintain locally, survey antigens in the epidermis, migrate to lymph nodes, and can present antigens to T cells. Langerhans cells therefore play an important role in the activation of proinflammatory adaptive immune responses and are critical in the response to pathogens and cancer. + +Langerhans cells are also important suppressors of the adaptive immune responses in the skin, contributing to immune tolerance and preventing excessive or unnecessary immune responses. They are capable of recognizing self-antigens and communicating the information to T cells, thereby generating tolerance and preventing autoimmune reactions. Furthermore, they play an important role in skin conditions such as psoriasis and skin cancers, frequently becoming the subject of research for treatments." DOI:10.1097/MOH.0000000000000202|DOI:10.1016/j.it.2017.06.008|DOI:10.3389/fimmu.2017.01941|DOI:10.1016/B978-0-323-31696-5.00009-7|DOI:10.3389/fimmu.2018.01768/full +320 CL:0000485 CL_0000485 "Mucosal type mast cells are a specific subtype of mast cells that are predominantly found in mucosal tissues, particularly the gastrointestinal and respiratory tracts. These cells produce tryptase, in contrast to connective tissue mast cells which additionally produce chymase and carboxypeptidases. Mucosal mast cells play an integral role in maintaining homeostasis and are therefore situated in locations most commonly exposed to antigens. + +The primary function of mucosal type mast cells is the rapid response to external pathogens and harmful substances, accomplished through their ability to secrete histamine and various proteases. These cells express receptors for immunoglobulin E (IgE), and upon cross-linking of their receptor-bound IgE by allergens or other antigens, degranulation occurs. During degranulation, pre-formed inflammatory mediators such as histamine, tryptase, and chymase are released to help neutralize the invading pathogens. This release triggers an immediate immune response characterized by increased vascular permeability, smooth muscle contractions, and recruitment of other immune cells to the site of infection or injury. + +Furthermore, mucosal type mast cells are well known to be part of the allergic response. They play a significant role in allergic conditions such as asthma and food allergies which are often associated with mucosal surfaces. Understanding the role of mucosal mast cells in allergic responses is an ongoing area of interest to improve treatment and prevention of anaphylaxis and other allergic reactions." DOI:10.1038/emm.2014.7|DOI:10.3389/fimmu.2015.00620/full|DOI:10.3390/cells8020135|DOI:10.1038/mi.2014.131|DOI:10.3390/cells11030329 +321 CL:0000492 CL_0000492 "The CD4-positive helper T cells are a subpopulation of T lymphocytes, which are part of the adaptive immune system. These cells play a vital role in establishing and maximizing the capability of the immune system to combat infections. Like all T lymphocytes, CD4+ helper T cells are uniquely characterized by the expression of a T-cell receptor (TCR) complex on their cell surface. The subset of CD4+ cells express the CD4 glycoprotein on their cell surface that serves as a co-receptor for the T-cell receptor. The CD4 co-receptor enables these cells to interact with antigen-presenting cells and perform their influential role in adaptive immune response. + +CD4+ helper T cells are primarily responsible for assisting other cells in the immunological processes. This involves recognition, interaction, and processing of antigens. Once an antigen-presenting cell presents a foreign antigen such as peptides derived from pathogens or transformed cells to the CD4+ helper T cell, it becomes activated, proliferates, and differentiates into subtypes such as Th1, Th2, Th17, or Treg, each with a specific role in the immune response. Th1 cells produces various cytokines. including IFN‐γ, IL-2 and TNF-β, and aid cell-mediated immune responses against intracellular pathogens. Th2 cells produce IL-4, IL-5 and IL13 and assist in antibody-mediated immune responses. + +Th17 cells release IL-17 and convey protective immunity against extracellular bacteria and fungi as well as contributing to inflammation and autoimmunity, while Treg cells are immunosuppressive cells and maintain immune homeostasis and provide tolerance to self-antigens. Finally, follicular T helper (Tfh) cells are thought to help B cells build up antibody responses by assisting germinal center formation, affinity maturation, and possibly immunoglobulin class switch recombination + +In addition to their critical role in immune response, CD4+ helper T cells are notably the main target of HIV infection, where the virus depletes the number of these cells, resulting in the deterioration of the immune system, characterized in the progression to AIDS. Thus, the presence and functionality of CD4+ helper T cells are not only necessary for a healthy immune response but also crucial in the context of immunodeficiency diseases. +" DOI:10.1111/imcb.12662|DOI:10.1002/ctd2.199|DOI:10.1146/annurev-immunol-103019-085803|https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/t-helper-cell|DOI:10.1038/s43018-023-00521-2 +322 CL:0000542 CL_0000542 "Lymphocytes are a type of leukocyte that play a significant role in the immune system. Lymphocytes are morphologically characterized by a single-lobed, large nucleus and relatively little cytoplasm. They include T cells, B cells, and innate lymphoid cells, which include natural killer (NK) cells. + +Innate lymphoid cells participate in the innate immune response and are partially responsible for the initial response to pathogens and damage, and for priming the adaptive immune response. NK cells in particular are important in the antiviral response. + +T and B lymphocytes comprise the adaptive immune system. These cells are responsible for recognizing and “remembering” antigens, producing antibodies, and targeting potentially harmful cells including virally infected cells or tumor cells. When activated, B cells transform into plasma cells that produce antibodies specific to particular antigens. T cells are broadly subdivided into CD4-expressing T helper cells, which are important for activating B cells, and CD8-expressing cytotoxic T cells, which can directly target infected cells." DOI:10.1016/B978-0-323-08593-9.00013-9|DOI:10.1016/B978-0-323-35762-3.00019-6|DOI:10.1016/B978-012088451-3.50005-3|DOI:10.1016/B978-0-323-04404-2.10002-8 +323 CL:0000546 CL_0000546 "T-helper 2 cells (Th2 cells) are a subset of CD4+ T lymphocytes, which play central roles in cell-mediated immunity. All T lymphocytes are uniquely characterized by the expression of a T-cell receptor (TCR) complex on their cell surface. Th2 cells express the CD4 co-receptor which enables the T-cell receptor to engage with antigen-presenting cells and perform their influential role in adaptive immune response. + +Th2 cells differentiate from naïve CD4+ T cells following TCR ligation and specific cytokine signaling. Th2 cell development and stabilization requires the master regulatory transcription factor GATA-3. Furthermore, IL-4-mediated activation of STAT6 is thought to play an important role in Th2 cell differentiation. + +The primary function of Th2 cells is to coordinate the immune response against extracellular pathogens, particularly parasitic helminths. They achieve this primarily through the secretion of their signature cytokines – the interleukins IL-4, IL-5, and IL-13. For instance, IL-4 promotes the differentiation of B cells into plasma cells that produce immunoglobulin E (IgE), a class of antibodies that mediate the immune response to parasites and are involved in allergic reactions. IL-5 promotes the activation and survival of eosinophils, a type of white blood cell that is effective against certain parasites. IL-13 works alongside IL-4 but also influences mucus production in the respiratory tract, an important defense mechanism against parasites. + +Despite their critical roles in host defense, an overactive Th2 response can also lead to pathological outcomes such as allergy and asthma. These health issues are typically characterized by excessive IgE production, eosinophilic inflammation, and mucus hypersecretion, all hallmarks of a Th2 response. In these instances, the immune system reacts excessively to normally harmless substances like pollen, dust mites, or certain foods, with the Th2 cells driving this overreaction. As such, understanding the precise pathways and mechanisms through which Th2 cells operate not only provides insight into protective immune responses but also potential therapeutic targets for treating allergies and other related conditions. +" DOI:10.1038/nri.2017.118|DOI:10.3389/fimmu.2019.02318|DOI:10.1146/annurev-immunol-051116-052350|DOI:10.3389/fimmu.2022.974066 +324 CL:0000576 CL_0000576 "Monocytes are a type of white blood cell that constitute part of the mononuclear phagocyte system. They feature prominently in the human body's first line of defense against foreign substances as a part of the innate immune system. Monocytes are the largest of all circulating leukocytes and are identified by their bean-shaped nucleus. They are produced in the bone marrow and circulate in the bloodstream; in some conditions, they may enter tissues and differentiate into macrophages or dendritic cells or a distinct monocyte-derived cell. + +Monocytes function effectively as phagocytes, devouring harmful pathogens in the body. They engulf and destroy microbes, foreign substances, cancer cells, and other materials detrimental to the body's well-being. This process, known as phagocytosis, is vital for the body's immune response. Monocytes are also equipped to identify harmful pathogens and alert other immune cells to their presence. This is achieved by producing proinflammatory cytokines that recruit other immune cells to the affected area, amplifying the immune response. + +Beyond their role in fighting infections, monocytes play an important role in the repair and healing of tissues. After an infection or inflammation subsides, monocytes can transition into different types of cells and assist in healing by clearing dead cells and debris and facilitating tissue regeneration. They are crucial in wound healing, control of microbial growth, and tissue development. " "DOI:10.1016/j.immuni.2018.10.005 +|DOI:10.1126/science.1178331|DOI:10.1146/annurev.immunol.021908.132557" +325 CL:0000624 CL_0000624 "CD4-positive, alpha-beta T cells, also known as the CD4+ αβ T cells, represent a subset of T lymphocytes that play a crucial role in the immune system's innate and adaptive response to pathogens. These cells are identified by the presence of the CD4 glycoprotein on their surface and the expression of alpha-beta (αβ) T cell receptors. The CD4 co-receptor assists in the recognition and binding to the MHC class II molecules on antigen-presenting cells, while the αβ T cell receptor is essential in identifying specific antigens presented by the MHC class II molecules. + +The primary contribution of the CD4-positive, alpha-beta T cells to the immune response is their role in ensuring a complete and effective immune reaction. Once activated by the detection of a bound antigen-MHC class II complex via their αβ T cell receptors, these cells differentiate into several subsets, including T helper 1 (Th1), T helper 2 (Th2), T helper 17 (Th17), and regulatory T cells (Tregs), as well as CD4+ effector and cytotoxic T cells. The cell fate of naïve CD4+ αβ T cells is determined by both the strength of interaction between TCR and antigen-MHC class II complex and the cytokine environment. For example, a naïve clone that receives a strong TCR signal in the presence of IL-12 and IFN-γ can develop into specific CD4+ effector cells, while a clone that receives a weaker TCR signal can differentiate into a Th1 helper cell. + +The different subsets that are derived from CD4-positive, alpha-beta T cells perform a unique function to orchestrate a comprehensive defense against infections. For example, Th1 cells are responsible for driving cellular immunity by activating cytotoxic T cells and macrophages, a mechanism particularly crucial in fighting intracellular pathogens like viruses or certain bacteria. Th2 cells trigger humoral immunity by inducing B cells to produce antibodies, thus targeting extracellular pathogens such as parasites. Th17 cells contribute to anti-fungal and anti-bacterial responses, but are also implicated in inflammatory and autoimmune conditions. Tregs help maintain self-tolerance and prevent an exaggerated immune response by inhibiting immune reactions against self and non-threatening antigens. + +Overall, CD4-positive, alpha-beta T cells through their various subsets maintain a balance between eradicating pathogens and preventing overactive immune responses that can damage the host's own cells. +" DOI:10.1146/annurev-immunol-103019-085803|DOI:10.3389/fimmu.2017.00019|DOI:10.1038/nri3152|DOI:10.1155/2012/925135|DOI:10.1038/s41577-018-0044-0 +326 CL:0000625 CL_0000625 "CD8-positive, alpha-beta T cells, also referred to as CD8+ T cells, are integral components of the body's adaptive immune system. They are characterized by the presence of the CD8 glycoprotein on their cell surface and the alpha and beta chains in their T cell receptors (TCRs). CD8+ T cells primarily function as cytotoxic T cells (CTLs), their specialized role in the immune response being to detect and eliminate cells presenting foreign or abnormal antigens on their surfaces. + +Naïve CD8+ T cells patrol the central lymphoid organs, checking peptide– MHC class I molecule complexes for the presence of their cognate antigen on antigen-presenting cells. Recognition of the foreign antigen by the TCR and interaction with MHC class I molecules triggers a series of events leading to the activation of the CD8+ T cell. Once activated, the CD8+ T cell divides, matures, and differentiates into effector T cells capable of destroying the target cells. This cytotoxic function is carried out by the release of substances like perforin and granzymes, which induce apoptosis, or programmed cell death, in the target cells. + +In addition to their cytotoxic function, CD8+ T cells are known to release various cytokines, including interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). These are potent mediators of the immune response and have roles in shaping the immune response and the inflammatory reaction. +Following the resolution of an immune response, a small subset of activated CD8+ T cells persists as memory T cells, providing a quicker and more vigorous response upon subsequent encounters with the same antigen. These capabilities make CD8-positive, alpha-beta T cells indispensable for the body's defense against infections and malignant transformations. +" DOI:10.1016/j.immuni.2011.07.010|DOI:10.3389/fimmu.2018.02692|DOI:10.1038/s41577-021-00574-3|DOI:10.3389/fimmu.2018.02826 +327 CL:0000767 CL_0000767 "Basophils are a type of granulocyte. They are the least common of the body's leukocytes, accounting for about 0.5% to 1% of all white blood cells. These cells are produced in the bone marrow and circulate throughout the bloodstream, but they are also found in tissues during allergic reactions. + +Basophils contain large granular structures filled with histamine and heparin. Upon encountering a foreign substance or in response to specific immune signals, basophils degranulate and release these mediators. Histamine is a substance that enhances the body's inflammatory response, leading to symptoms such as swelling, redness, and itching. Heparin, an anticoagulant, helps to prevent blood clotting. + +Basophils are also known to promote type 2 immune responses by releasing cytokines such as IL-4. Basophils thus play a crucial role in fighting parasitic infections and in allergic responses. They are capable of identifying parasites and then releasing a type of antibody known as immunoglobulin E (IgE) which coats the parasite. This action triggers an immune response from other cells, leading to the destruction of the parasite. The ability of basophils to respond to such infections makes them an essential part of the body's immune defense system. The exact triggers that cause basophil activation can vary and may include allergens, particular immune system molecules, or certain drugs." DOI:10.3389/fimmu.2022.1056838|DOI:10.1016/j.jaci.2013.07.046|DOI:10.1016/j.smim.2021.101529|DOI:10.3389/fimmu.2022.902494|DOI:10.1016/j.ejphar.2015.04.049 +328 CL:0000782 CL_0000782 "Myeloid dendritic cells are a subset of dendritic cells derived from the common myeloid progenitor cell. ""Conventional"" and ""myeloid"" DCs are often used interchangeably. In contrast, dendritic cells may also arise from the common lymphoid progenitor. Monocyte-derived dendritic cells may also be induced by inflammatory states. + +Dendritic cells function as antigen-presenting cells and are able to activate naïve T cells to induce the adaptive immune response. Dendritic cells capture, process, and present antigens derived from pathogens to mount a specific immune response against the invading antigen. Dendritic cells also produce a range of cytokines that help in modulating and recruiting other immune cells during an immune response. + +Dendritic cells can contribute to immune tolerance by deleting self-reactive T cells or by inducing regulatory T-cells, thereby preventing autoimmunity. Dendritic cells thus are important in orchestrating the adaptive immune response and are pivotal in combating infections and maintaining tolerance to self." DOI:10.1016/j.imbio.2014.12.010|DOI:10.1016/j.immuni.2007.06.006|DOI:10.1111/imm.12888|DOI:10.1002/jlb.66.2.205|DOI:10.3389/fimmu.2018.03176 +329 CL:0000771 CL_0000771 "Eosinophils are a type of granulocyte derived from myeloid progenitors in the bone marrow; they are a part of the body's immune system. Named for their affinity to eosin, a red acidic dye used in staining procedures, eosinophils contribute to the immune system's response by migrating to inflammation sites, particularly those produced by allergic reactions and infections due to multicellular parasites. They comprise ~1-5% of the white blood cells in circulation. + +Eosinophils play crucial roles in mediating inflammatory responses. They carry granules containing a variety of enzymes and proteins, including major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN). These enzymes and proteins are effective in killing bacteria, parasites, and some cancer cells. When exposed to an antigen, eosinophils degranulate and release these mediators to the site of infection, resulting in the destruction of invading microorganisms. Specifically, in parasitic infections, eosinophils attach themselves to the parasites and release these cytotoxic granules, causing a lethal rupture in the parasite's surface. Eosinphils may also release cytokines to attract other immune cells to sites of infection and to skew the response towards type 2 immunity. + +Eosinophils are also involved in conditions such as asthma and allergic reactions. They secrete chemical mediators such as leukotrienes and prostaglandins that trigger contraction of smooth muscles, causing symptoms such as bronchoconstriction observed in asthma. However, these multifunctional cells, while useful in defending the body, may also inadvertently cause tissue damage if excessively activated. Increased numbers of eosinophils, a condition known as eosinophilia, can indicate a variety of diseases including allergies, skin disorders, parasitic and fungal infections, autoimmune diseases, certain types of cancer, and asthma." DOI:10.1146/annurev-pathmechdis-012419-032756|DOI:10.1016/j.mayocp.2021.04.025|DOI:10.1038/nri3341|DOI:10.1182/blood-2012-06-330845|DOI:10.1128/microbiolspec.mchd-0020-2015 +330 CL:0000766 CL_0000766 "Myeloid leukocytes are a group of immune cells descended from the myeloid lineage. The myeloid lineage constitutes a significant portion of the body's defense system, particularly against microbial pathogens and foreign substances. Myeloid leukocytes originate from hematopoietic stem cells located in the bone marrow. The commitment of a pluripotent hematopoietic stem cell into a myeloid progenitor cell represents the initiation step towards the development of myeloid leukocytes. Once differentiated, these cells contribute diversely to both the innate and adaptive immune responses in the body. + +Myeloid leukocytes include several distinct cell types based on functionality and structure, encompassing monocytes, macrophages, granulocytes (neutrophils, eosinophils, and basophils), and dendritic cells. Each cell type has specialized functions, occupying a unique role in the body's immune response. For instance, neutrophils are prolific phagocytes—cells that engulf and destroy pathogens—while eosinophils are instrumental in combating multicellular parasites and modulating allergic inflammatory responses. Monocytes, in addition to their phagocytic activities, can enter peripheral tissues and differentiate into macrophages or dendritic cells which are crucial for antigen presentation to T cells. + +Another critical function of myeloid leukocytes is their involvement in tissue remodeling and repair. For example, macrophages not only play a key role in defending the body but also perform duties essential for wound healing, such as removing dead cells and stimulating tissue repair. In general, myeloid leukocytes participate in the removal of old and damaged cells, an essential process for maintaining good health and homeostasis. Through the orchestration of complex interactions and signal transductions, myeloid leukocytes provide the body with a robust defense system against foreign invaders and participate in maintaining the body's overall balance and function." DOI:10.1016/j.biocel.2004.01.020|https://www.ncbi.nlm.nih.gov/books/NBK563148/ +331 CL:0000776 CL_0000776 "An immature neutrophil, also known as a band neutrophil or band cell, is an intermediary stage in neutrophilic granulocyte development. Immature neutrophils are formed in the bone marrow then released into the bloodstream where they eventually mature into functional, mature segmented neutrophils. They are characterized by an unsegmented, curved nucleus, a distinguishing factor that differentiates them from mature neutrophils, which possess a multi-lobed nucleus. + +Immature neutrophils can be found in circulation, but their numbers may increase drastically during infection. These cells are released from the bone marrow as a result of emergency granulopoiesis. The role of these cells in infection and acute inflammation remains controversial, and it has been suggested that these cells could possess immunosuppressive or proinflammatory activity. + +An increase of immature neutrophils in the bloodstream, a condition referred to as bandemia or a left shift, can be an important clinical indicator. While low-level presence is typical, an abnormally high count can signal severe or systemic bacterial infection, inflammation, or less commonly, diseases that affect bone marrow function such as leukemia. However, not all bacterial infections will result in a left shift." DOI:10.1016/j.it.2019.04.012|DOI:10.1016/j.it.2019.04.013|DOI:10.3389/fimmu.2020.01259/full|DOI:10.1016/j.cca.2016.03.017 +332 CL:0000784 CL_0000784 "Plasmacytoid dendritic cells (pDCs), initially known as interferon-producing cells, are a unique subpopulation of dendritic cells. Unlike conventional dendritic cells (cDCs), plasmacytoid dendritic cells are characterized by their distinctive plasma cell-like morphology. These cells play vital roles in the innate and adaptive immune response, particularly in the antiviral response. Highly prevalent in the blood and lymphoid organs, pDCs are rare in non-lymphoid tissues, with the exception of inflamed tissues and tumors where they are often recruited. + +A key role of plasmacytoid dendritic cells is their rapid and robust production of type 1 interferons in response to viral infections. This is crucial for antiviral defense as interferon signals to other immune cells to increase their antiviral defenses. pDCs achieve this by detecting viral nucleic acids in the cytosol through Toll-like receptors (TLRs), specifically TLR7 and TLR9. Upon recognition, these cells quickly produce substantial amounts of interferons, which plays a significant role in the containment of viral replication and the development of acquired antiviral immunity. + +The potential of plasmacytoid dendritic cells for antigen presentations to naive T cells is relatively low under steady-state conditions. Upon activation by certain stimuli, such as viruses or CpG oligodeoxynucleotides, they have the ability to differentiate into efficient antigen-presenting cells. This transition to activated cells involves an upregulation of major histocompatibility complex (MHC) class II molecules and co-stimulatory molecules, thus allowing them to effectively present antigenic peptides to naive T cells. This crucial function in linking innate and adaptive immunity underlines the importance of pDCs to the overall immune response." DOI:10.1016/j.immuni.2018.12.027|DOI:10.1038/nri3865|DOI:10.1016/j.immuni.2007.06.006|DOI:10.1016/bs.ircmb.2019.07.004 +333 CL:0000775 CL_0000775 "Neutrophils are an essential component of the human immune system and belong to the category of white blood cells known as granulocytes. They constitute approximately 50-70% of all white blood cells, making them the most abundant type of immune cells in mammals. Neutrophils develop in the bone marrow from hematopoietic stem cells before being released into the bloodstream where they circulate before migration into tissues, thereby exhibiting a multi-step process that includes margination, rolling, adhesion, and transmigration. + +Phenotypically and functionally, neutrophils represent a heterogeneous cell population. They are the immune system’s immediate responders and are the first cells to migrate towards the site of an infection. They play a critical role in defending the body from potential pathogenic bacteria and fungi. Their primary mechanism of action involves phagocytosis, where they engulf and destroy these microbes. Neutrophils are characterized by the presence of large quantities of granules containing antimicrobial proteins and enzymes, including defensins and myeloperoxidase, which are released once the cell has recognized and attached to the microbes. The enzymes and other antimicrobial agents can also be released into the surrounding environment, a process known as degranulation. + +Neutrophils also possess the unique biological ability to eliminate pathogens through a process called neutrophil extracellular trap (NET) formation, or NETosis. In this process, neutrophils release a mixture of DNA, histones, and granule proteins that form a web-like structure which traps and kills microbes. Notably, this process usually leads to the death of the neutrophil itself, referred to as cell suicide or programmed cell death. + +Neutrophils play a crucial role in the immune system by rapidly responding to infections and inflammation, excessive or dysregulated neutrophil activity can contribute to tissue damage and chronic inflammation, exacerbating various diseases such as rheumatoid arthritis, and neutrophils may contribute to tumor growth and progression. +" "DOI:10.1038/s41577-019-0141-8|DOI:10.3389/fphys.2018.00113|DOI:10.1111/febs.15803|DOI:10.1007/s10753-016-0458-4|DOI:10.1038/s41577-021-00571-6 + +" +334 CL:0000791 CL_0000791 "Mature alpha-beta T cells, also known as αβ T cells, are critical components of the adaptive immune system, responsible for a mediated immune response to pathogens and infected body cells. They derive their name from the alpha and beta chains that make up their characteristic T-cell receptor (TCR), a protein complex that binds to antigens. These cells undergo a maturation process in the thymus, where they learn to recognize self-antigens, thus achieving self-tolerance. + +Maturation of alpha-beta T cells takes place in the thymus and is tightly controlled by various transcriptional and epigenetic regulators. They develop through several stages from progenitors to mature T cells, from CD4-CD8- double negative cells to CD4+CD8+ double positive cells, until they eventually become CD4+ or CD8+ single positive cells. + +Once matured, alpha-beta T cells primarily serve as regulators and effectors in an immune response. They are adept at recognizing fragments of antigens, often viruses or bacteria, presented on the surface of other cells via major histocompatibility complex (MHC) molecules. Once they encounter and recognize an antigen, they become activated, proliferate and differentiate into distinct subsets of effector T cells, such as cytotoxic T cells, helper T cells, and Natural Killer (NK) cells, each with a specific role in immune response. + +Cytotoxic T cells, the effector cells for cell-mediated immunity, are adept at killing cells that have been infected, particularly with viruses. They do this by binding to infected cells and releasing cytotoxic substances which induce apoptosis, or cell death, thus eliminating the infected cells. The main function of NK cells is to kill virally infected cells, and to detect early signs of cancer. Helper T cells do not kill infected cells directly but play a key role in modulating or orchestrating the immune response by releasing cytokines that recruit and regulate other immunity cells such as B cells and macrophages. Therefore, the versatile roles of mature alpha-beta T cells are vital for maintaining the body's successful adaptive immune defenses. +" https://www.sciencedirect.com/topics/immunology-and-microbiology/alpha-beta-t-cell|DOI:10.1038/s41392-023-01471-y|DOI:10.1016/j.immuni.2018.01.007|DOI:10.3389/fimmu.2022.884569 +335 CL:0000789 CL_0000789 "Alpha-beta T cells, or αβ T cells, are a subtype of T lymphocytes that play a key role in the adaptive immune system. Found in the vertebrate's system, these specialized T cells are characterized by the expression of alpha (α) and beta (β) chain T cell receptors (TCRs) on their cell surface that enables them to detect and respond to foreign or abnormal antigens presented by major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells (APCs). Named after their αβ TCRs, these cells are trained to recognize specific antigens and respond accordingly to safeguard the body against pathogenic threats. In contrast to their less abundant counterparts, the gamma-delta (γδ) T cells, αβ T cells can only recognize antigen that is bound to an MHC molecule. + +The population of alpha-beta T cells is diverse and these cells are mainly classified into two groups: CD4+ αβ T cells and CD8+ αβ T cells. Naïve CD4+ αβ T cells patrol the central lymphoid organs, checking peptide– MHC class II molecule complexes on antigen-presenting cells for the presence of their cognate antigen. Following antigen recognition by the TCR and activation, these cells differentiate into CD4+ helper T cells or regulatory T cells. In contrast, naïve CD4+ αβ T cells detect antigens presented by MHC class I molecule, and following activation, they differentiate into cytotoxic T lymphocytes (CTLs). + +Depending on the subtype, differentiated αβ T cells have a wide range of different functions. T helper cells produce cytokines after they recognize specific antigens, thereby, providing help to other immune cells like B cells, which are required to produce antibodies, and phagocytes to destroy the engulfed invaders. CTLs, on the other hand, destroy cells infected with viruses or other pathogens and cells that are damaged or dysfunctional. Collectively, they are essential for the body's primary defense against intracellular pathogens, such as viruses and some bacteria. + +While these activated effector cells are usually short-lived, a proportion survive as memory T cells which have the ability to remember specific antigens after an infection, thereby providing long-term immunity against these specific pathogens. +" https://www.sciencedirect.com/topics/medicine-and-dentistry/alpha-beta-t-cell|DOI:10.1038/s41392-021-00823-w|DOI:10.1016/j.it.2018.05.005|DOI:10.1038/s41392-023-01471-y +336 CL:0000790 CL_0000790 "Immature alpha-beta T cells represent a subpopulation of T cells in the thymus that are at a development stage in which they are yet to attain full functional status. The term 'alpha-beta' refers to the two distinct types of chains, alpha (α) and beta (β), which form the T cell receptor (TCR) located on the cell's surface. This T cell receptor enables the cell to identify and bind to specific antigens in order to initiate an immune response. + +Immature alpha-beta T cells arise from lymphoid progenitor cells in the bone marrow and migrate to the thymus, where the maturation of T cells takes place. In the thymus, immature cells (thymocytes) undergo a series of division and differentiation events characterized by the rearrangement of their TCR genes. Upon successful recombination, the cells express a functional alpha-beta TCR on their surface and can then be subjected to a process of selection based on the specificity of the newly expressed receptors. These stages of development are critical to ensuring that only cells with a suitable TCR repertoire survive, ready to be deployed within the immune system. + +Multiple subsets of immature alpha-beta T cells can be distinguished, depending on the developmental and differentiation stage, including CD4+CD8+ double positive thymocytes, CD4+ or CD8+ single positive thymocytes and immature NK T cells. + +Immature alpha-beta T cells are critically important to immune function. They constitute the foundation for the adaptive immune system - a fundamental component in combating pathological agents. Once fully matured, these cells can differentiate further into effector T cell types (like helper, cytotoxic, and regulatory T cells), each having unique functional roles in an immune response. The proper development of immature alpha-beta T cells is fundamental to the overall health and efficacy of the immune system. +" https://www.sciencedirect.com/topics/immunology-and-microbiology/alpha-beta-t-cell|DOI:10.1038/s41392-023-01471-y|DOI:10.1016/j.immuni.2018.01.007|DOI:10.3389/fimmu.2022.884569|DOI:10.1016/j.immuni.2020.03.019 +337 CL:0000792 CL_0000792 "The CD4-positive, CD25-positive, alpha-beta regulatory T (Treg) cell serves as a vital element in the mammalian immune system, playing a pivotal role in maintaining immune homeostasis and preventing autoimmunity. This particular T regulatory cell is characterized by CD4 proteins and a high level of CD25 (the alpha chain of the interleukin-2 receptor) on its cell surface. The T-cell receptor (TCR) of these Treg cells is composed of alpha and beta protein chains, making them a subtype of the alpha-beta T cell population that recognize and bind to antigens presented by MHC class II molecules. + +The primary function of CD4-positive, CD25-positive, alpha-beta Treg cells is regulating immune responses, ensuring that the immune response is proportionate and preventing autoimmunity, maintaining peripheral immune tolerance, and limiting chronic inflammation. They achieve this regulation by suppressing or downregulating the proliferation of effector immune cells, which are activated in response to antigens, to prevent their excessive or uncontrolled activity. + +CD4-positive, CD25-positive, alpha-beta Treg cells can suppress immune responses via a variety of mechanisms, including the release of inhibitory cytokines, in particular IL-10 and TGFβ, or through cytolysis of effector immune cells (e.g. antibody-producing B cells) involving perforin and granzymes. They can also modulate the maturation or function of dendritic cells, which are key antigen-presenting cells, and thereby reduce their ability to stimulate effector T cells. + +This downregulation also suppresses effector T cell functions against self-antigens—proteins that are innate to the body—to prevent autoimmunity. In essence, Treg cells act as a policing force within the immune system to maintain balance and prevent overreaction which can potentially lead to damaging effects. + +Besides their crucial role in preventing autoimmunity, CD4-positive, CD25-positive, alpha-beta Treg cells contribute to other functions such as tumor immune evasion, maternal-fetal tolerance, and transplantation tolerance. By suppressing the cytotoxic T cell response, these cells may inadvertently help tumor cells evade destruction, contributing to cancer progression. However, this characteristic can be potentially manipulated for therapeutic applications in immune-related diseases or transplantation, further highlighting the potential and importance of CD4-positive, CD25-positive, alpha-beta regulatory T cells in immune regulation. + +" DOI:10.3389/fimmu.2019.03100|DOI:10.1038/nri2343|DOI:10.1146/annurev-immunol-042718-041717|DOI:10.3389/fimmu.2021.750542|DOI:10.1016/j.immuni.2019.01.020 +338 CL:0000796 CL_0000796 "CD8-alpha-beta-positive, alpha-beta intraepithelial T cells are subpopulation of αβ intraepithelial lymphocytes (IELs) which are predominately found in the intraepithelial layer of the intestine, skin and lung. They are characterized by the cell surface expression of both αβ T cell receptors (TCRs) and the CD8 αβ co-receptors, which are responsible for recognizing specific antigens expressed on the surface of pathogenic cells. + +The primary function of CD8-alpha-beta-positive, alpha-beta intraepithelial T cells revolves around providing immune protection by targeting and eliminating cells infected with viruses or other pathogens. The TCR-CD8 complex on their surfaces recognizes major histocompatibility complex (MHC) class I molecules on infected cells. After recognition, the T cells bind to the infected cells and release cytotoxic agents that trigger apoptosis, leading to the death of the infected cells and effectively curbing the spread of the invading pathogen. This process also helps create a memory response for the same pathogens, enabling quicker responses in subsequent encounters. + +With a majority of pathogens entering the body through the epithelial surfaces like skin and mucous membranes, having these T cells strategically located in these layers enables an effective first line of defense. Apart from pathogen detection and removal, they also contribute to maintaining tissue integrity and providing a surveillance mechanism against tumorigenic cells. +" "DOI:10.3389/fimmu.2022.1059042|DOI:10.1038/s41385-020-0294-6 + +|DOI:10.1038/s41385-018-0016-5" +339 CL:0000794 CL_0000794 "The CD8-positive, alpha-beta cytotoxic T cell plays a crucial role in the immune response system of vertebrates. A key feature of these cells is the expression of CD8, a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor (TCR). Notably, the alpha-beta refers to the TCR heterodimer on the T cell, utilized to recognize the antigens displayed by Major Histocompatibility Complex (MHC) class I molecules on antigen-presenting cells. + +Functioning primarily to combat intracellular pathogens, CD8+ T cells primarily seek and destroy cells infected by viruses or transformed by cancer. The TCR on the CD8+ T cell recognizes and binds to the antigen-MHC I complex displayed on the infected cell’s surface. Following this interaction, along with the engagement of co-stimulatory molecules, the T cell becomes activated. Upon activation, the CD8+ T cell proliferates and differentiates into cytotoxic T lymphocytes (CTL), ready to survey the body for the recognized antigen. + +CTLs employ two major cytotoxic mechanisms: the release of cytotoxic granules and the expression of death-inducing ligands on their surface. Cytotoxic granules contain perforin, a protein that forms pores in the targeted cell membrane, and granzymes, enzymes that trigger apoptosis inside the targeted cell through the activation of caspases. The Fas ligand and TRAIL death-inducing ligands on CTLs also bind to their respective receptors on the target cell and initiate a caspase cascade leading to cell death of the target. This cytotoxic function of the CD8+ alpha-beta T cell is critical in the control of infections and in cancer surveillance. + +" DOI:10.3389/fimmu.2022.883010|DOI:10.1038/s12276-023-01105-x|DOI:10.3389/fmolb.2021.628332|https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/cytotoxic-t-cell +340 CL:0000798 CL_0000798 "Gamma-delta T cells, also referred to as γδ T cells, are a distinct subset of T lymphocytes that play unique roles in the immune system. They are defined by expression of heterodimeric T-cell receptors (TCRs) comprised of γ and δ chains. They share characteristics with both innate and adaptive immune cells, and unlike alpha-beta (αβ) T cells, they do not require antigen processing and Major Histocompatibility Complex (MHC) presentation for the recognition of antigens. This unique response mechanism allows them to contribute to rapid immune responses, particularly in the context of tissue injury and infection. + +Depending on the γδ TCR and the context, different subsets of gamma-delta T cells perform a variety of functions which range from regulating thermogenesis in adipose tissue to controlling the plasticity of neuronal synapses in the central nervous system. A key function is in tissue homeostasis and surveillance against infectious agents and tumors. + +They can carry out their defense role through several mechanisms, such as cytokine production, killing of target cells, and regulation of other immune cell responses. In response to pathogens, these cells produce a wide range of cytokines, including interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-17 (IL-17), which help recruit and activate other immune cells to the site of infection. Furthermore, gamma-delta T cells can directly kill infected cells or cancerous cells, which is instrumental in preventing the spread of infection or malignancy. + +Despite the broadly generalized role in immunity, the function of gamma-delta T cells can vastly vary depending on their tissue location. In the skin and mucosal tissues, they provide quick response to pathogens, while in secondary lymphoid organs, their regulatory functions shape the adaptive immune response. In recent years, their role in the context of autoimmunity and cancer has gained attention, with emerging studies suggesting their potential for immunotherapeutic interventions. Thus, gamma-delta T cells serve as vital components of the immune system, providing a versatile defense mechanism against a range of pathogenic targets. +" DOI:10.1038/s41577-020-00452-4|DOI:10.1038/s41571-022-00722-1|DOI:10.1146/annurev-immunol-032713-120216|https://www.mdpi.com/journal/cells/special_issues/delta_T|DOI:10.1073/pnas.1818488116 +341 CL:0000797 CL_0000797 "Alpha-beta intraepithelial T cells, often referred to as αβ intraepithelial lymphocytes (IELs), are a distinct population of lymphoid immune cells found predominately along the intestinal epithelial layer. These specialized T cells play a pivotal role in the maintenance of the gut's immune homeostasis. These T cells are characterized by their αβ T cell receptor (TCR) which is responsible for recognizing specific antigens expressed on the surface of pathogenic cells. + +Subsets of αβ IELs are often classified into two main categories based on how the mode of selection in the thymus, and consequently their functional potential: Induced αβ IELs develop from conventional αβ+ T cells that express CD4 or the CD8αβ heterodimer. Once activated in response to peripheral antigens, they migrate to the intestine where they play a crucial role in the adaptive immune response. In contrast to induced, conventional IELs, natural αβ IELs are thought to acquire their phenotype after encountering self-antigen in the thymus. There is some evidence that they are CD4-negative, CD8-negative, alpha-beta intraepithelial T cells and are activated in a TCR-independent manner. In humans, induced CD8-alpha-beta-positive, alpha-beta intraepithelial T cells make up the largest subset of IELs (80%), while in mice, most of the IELs belong to a specific subpopulation of (natural) CD8-alpha-alpha-positive, alpha-beta intraepithelial T cells, a population whose existence in human remains controversial. + +Functionally, alpha-beta intraepithelial T cells are effectively positioned at the body's largest environmental interface, the gut mucosa. This strategic location allows them to act as first responders during pathogenic invasion. Upon activation, these cells can immediately react and eliminate intruding pathogens, thus reducing the chance of systemic infection spreading across the body. They not only contribute to immunosurveillance by detecting abnormal cells or foreign invaders, but they also have regulatory properties, helping to maintain the balance between tolerance and immunity in the intestine. + +Furthermore, alpha-beta intraepithelial T cells play a pivotal role in maintaining tissue homeostasis. They help in epithelial cell repair and renewal, utilize various mechanisms to limit inflammation, and contribute to the immune regulation of the gut microbiota. Apart from the intestinal epithelium, αβ IELs are also present in the skin and lung epithelium, suggesting their widespread involvement in tissue protection. The dysregulation of these cells is associated with several disorders, including inflammatory bowel disease, celiac disease, and cancer, indicating their importance in the health and disease of the gut. +" "DOI:10.3389/fimmu.2022.1059042|DOI:10.1038/s41385-020-0294-6 + +|DOI:10.1038/s41385-018-0016-5|https://www.sciencedirect.com/topics/immunology-and-microbiology/intraepithelial-lymphocyte" +342 CL:0000801 CL_0000801 "Gamma-delta intraepithelial T cells, also known as γδ intraepithelial lymphocytes (IELs), are a unique subset of T cells residing in the epithelial layer of mucosal tissues such as the intestine and skin; more are found in intestinal intraepithelial tissue than in other tissues. They are characterized by their distinct T-cell receptor (TCR) that is composed of one gamma (γ) and one delta (δ) chain, unlike the conventional alpha-beta T cells. Most γδ IELs also express the CD8-alpha-alpha homodimer (Cd8-alpha alpha positive, gamma-delta intraepithelial T cells), although some are lacking both co-receptors CD4 and CD8 (CD4-negative CD8-negative gamma-delta intraepithelial T cells). γδ IELs are though to be ‘natural’ IELs as they acquire their activated phenotype in an ‘alternative’ self-antigen-based maturation process in the thymus. + +Although the function of γδ IELs is still not fully established, current evidence indicates that they serve as a crucial first line of defense against invading pathogens, thus making them an important class of immune cells at the epithelial barrier interfaces. γδ IELs respond to a variety of antigens, including those not recognized by conventional T cells. They are also thought to be involved in recruiting in immune surveillance by promoting homeostasis of host microbiota and in limiting excessive inflammation. + +In addition to their primary role in immunity, γδ IELs also have roles in epithelial cell homeostasis and repair. They assist in maintaining the epithelial barrier by controlling the equilibrium of epithelial cell growth and death. They also contribute to the healing of lesions and the replacement of damaged epithelial cells. The regulative control exerted by γδ IELs over epithelial cell turnover indirectly influences immunity, underlining the complexity and versatility of these cells. +" DOI:10.3390/cells9030686|DOI:10.3389/fimmu.2022.1059042|DOI:10.1038/s41385-020-0294-6 +343 CL:0000802 CL_0000802 "The CD8-alpha alpha positive, gamma-delta intraepithelial T cell are a subset of intraepithelial lymphocytes (IELs), a highly heterogeneous population of immune cell that resides within the epithelial layer of mucosal barriers. CD8-alpha alpha positive, gamma-delta intraepithelial T cell are predominantly found in the gastrointestinal tract. They are characterized by the expression of both CD8-alpha-alpha homodimer and the gamma-delta (γδ) variant of the T cell receptor (TCR). CD8-alpha alpha positive, gamma-delta are thought to represent the most typical γδ IEL subset in the intestine. + +The IELs in the intestines are constantly and directly exposed to antigens in the gut lumen and form the first line of immune defense against invading pathogens. Unlike conventional T cells, IELs in the intestine are antigen-experienced and do not require priming. CD8-alpha alpha positive, gamma-delta intraepithelial T cells fall into a subgroup of ‘natural’ IELs, which acquire their activated phenotype in an ‘alternative’ self-antigen-based maturation process in the thymus. + +CD8-alpha alpha positive, gamma-delta intraepithelial T cell have several key functions. They help maintain the integrity of the epithelium and repair the epithelial barriers in response to physical and inflammatory injury by secreting various factors, including TGFβ1, TGFβ3 and keratinocyte growth factor (KGF). These cells also provide immediate, front-line defense against pathogens. They retain the ability to respond directly to stress-associated and infected cells independent of antigen-presenting cells and major histocompatibility complex molecules. They do this through recognition of antigens present on the surfaces of stressed or infected cells. Once activated, these cells initiate a rapid immune response by releasing cytotoxic granules and engaging death receptors, processes that eliminate harmful cells. Furthermore, CD8-alpha alpha positive, gamma-delta intraepithelial T cells have been implicated in regulatory functions, including in antibody class switching and immunoglobulin A (IgA) production and IL-10-dependent oral tolerance. + +Dysregulation CD8-alpha alpha positive, gamma-delta intraepithelial T cells is linked to several inflammatory disorders including celiac disease, inflammatory bowel disease, and others. Therefore, the CD8-alpha alpha positive, gamma-delta intraepithelial T cell plays a significant role in not only direct pathogen defense but also in the maintenance of epithelial tissue integrity and homeostasis. +" DOI:10.1038/nri3007|DOI:10.3390/cells9030686|DOI:10.1038/nri.2017.101|DOI:10.3389/fimmu.2022.1059042 +344 CL:0000800 CL_0000800 "Mature gamma-delta (γδ) T-cells represent a distinct subgroup within the diverse T-cell lineage. They are rare in secondary lymphoid organs but enriched in many peripheral tissues, such as the intestines, lungs and skin, where they play key immunological roles in the protection against infections and tumors, tissue healing, and immune regulation. They are ‘unconventional’ T cells defined by the expression of T-cell receptors (TCRs) that are heterodimers composed of γ and δ chains. + +Unlike their alpha-beta (αβ) T-cell counterparts, which recognize antigens via Major Histocompatibility Complex (MHC) molecules, γδ T-cells are activated in an MHC-independent manner perceive their targets in a more direct manner, reacting to stress-induced self molecules or unprocessed antigens, providing a more rapid immune response. + +Mature γδ T-cells derive from double-negative CD4− CD8− (DN) thymocytes, which can give rise to either αβ T or γδ T cell lineages. γδ T cells then develop from this precursor following a single selection step mediated by the γδ TCR; unlike cells in the αβ T cell lineage, they do not progress through to a double positive stage. Instead, most γδ T cells remain double-negative and develop into mature γδ T cells before they egress from the thymus. + +Upon maturation, γδ T-cells characteristics of both innate and adaptive immunity and can have both pro- and anti-inflammatory functions. Mature γδ T-cells fall into distinct IFNγ- and IL-17A-producing cell populations that can be distinguished by CD27 and CCR6 expression, respectively. The mature γδ T-cell population also includes γδ intraepithelial T-cells and dendritic epidermal T cells (DETCs), which are only present in the epidermis of rodents. + +These phenotypically different mature γδ T-cells are functionally versatile. In addition to their role in immunosurveillance against microbes and tumor cells, aiding in early defense against invaders. They produce a cytokine and chemokine response and exert cytolysis of infected or transformed target cells (involving perforin and granzymes). They can assist with tissue repair in certain organs like the skin and muscle due to their ability to produce growth factors. In humans, specific γδ T-cells are able to serves as professional antigen presenting cells. Finally, because these cells are able to recognize and lyse tumors in an MHC-unrestricted manner, they have a huge potential for pan-population tumor immunotherapy. +" DOI:10.1016/j.smim.2022.101662|DOI:10.3389/fimmu.2020.00042|DOI:10.3389/fimmu.2023.1106652 +345 CL:0000813 CL_0000813 "Memory T cells are a subpopulation of mature T lymphocyte cells that play a critical role in the immune response system. They develop following exposure to a new antigen: After antigen-driven expansion of naïve T cells and antigen clearance through effector T cells, some of the remaining T cells differentiate into memory T cells. Key to their function is their ability to ‘remember’ this antigen, allowing them to respond more rapidly and effectively upon subsequent exposures. These memory T cells remain in the body long-term, frequently for a lifetime, providing enduring immunity to the diseases caused by specific pathogens. + +Memory T cells can be divided into several main subclasses based on their location and functionality. Central memory T cells (Tcm) reside primarily in lymph nodes and other lymphoid organs. They typically express CCR7 and CD62L, which facilitate homing to secondary lymphoid organs. Upon secondary exposure to the antigen central memory T cells prolifically produce new effector cells, which are capable of rapidly mounting an immune response. Effector memory T cells (Tem) are predominantly present in peripheral tissues. They express chemokine receptors and integrins, allowing them to migrate to inflamed tissues and execute a potent immune response, such as cytotoxic attacks on infected cells, when they encounter a known antigen. Another subclass, tissue-resident memory T cells (Trm), take up long-term residence within a peripheral tissue where they can quickly execute a robust immune response when they encounter a pathogen in non-lymphoid tissue. Furthermore, memory regulatory T cells (Tre), which have been identified more recently, are thought to persist in the absence of antigen expression and may help suppress excessive immunopathological effects upon new exposure to the known antigen. + +The longevity and sensitivity of memory T cells make them integral components of vaccine strategies. Vaccines are essentially designed to elicit a robust pool of memory T cells capable of offering protective immunity against targeted infectious diseases. Disorders of memory T cells, including inadequate numbers and decreased functional capacities, are associated with immunological diseases, aging, and chronic infections. Therefore, a good understanding of memory T cells forms the basis for developing therapeutic interventions against various infectious diseases and immunological disorders. +" "DOI:10.1016/j.immuni.2018.02.010|DOI:10.1038/s41590-023-01510-4 + +|DOI:10.3389/fimmu.2018.02692|https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/memory-t-cell|DOI:10.1111/imr.13229" +346 CL:0000814 CL_0000814 "Mature NK T cells, or natural killer T cells, are a unique subset of alpha-beta T cells that serve as mediators in the immune response. They are named for their distinct ability to express markers typical of natural killer (NK) cells (such as NK1.1) as well as a T cell receptor specific for a limited set of ligands. + +Similar to mature effector T cells, mature NK T cells represent a heterogeneous group of effector cells, which express different transcription factors and cytokines and hence have different effector functions in both innate and adaptive immune responses. They are CD1d-restricted T lymphocytes: they recognize endogenous and exogenous lipid antigens presented by the MHC-like molecule CD1d. They have been classified into two subpopulations based on their TCR usage and specificity for lipid antigen: Type I NK T cells have an invariant TCRα-chain while type II NK T cells have a more diverse TCR repertoire. + +Mature NKT cells have been shown to have both pro- and anti-inflammatory functions and modulate immune responses, including cancer, autoimmunity, allergy, infection and graft-versus-host disease. The primary function of mature NK T cells is to rapidly respond to infections by releasing large amounts of cytokines to aid cell-to-cell communication in immune responses. They also play a role in recognizing and eliminating certain types of cancer cells. Upon activation via their TCRs, mature NK T cells can promptly release a plethora of cytokines including interferon-γ (IFN-γ) and interleukin-4 (IL-4). These cytokines subsequently stimulate other immune cells, such as B cells, T cells and macrophages, to respond to the infection or abnormal cell growth. + +In addition to antibody-mediated responses, NK T cells are capable of cytotoxic responses, a crucial function in managing viral infections. Mature NK T cells can bind to infected cells, inducing cell death and thereby preventing the spread of the infection. Furthermore, they have been found to play an instrumental role in autoimmunity and allergic diseases, highlighting their key part in maintaining the body’s overall immune balance. Continuous research on mature NK T cells informs therapeutic efforts in immunological disorders, infections, and cancer. +" "https://www.ncbi.nlm.nih.gov/books/NBK532332/|DOI:10.3389/fimmu.2018.00367|DOI:10.1128/cmr.00232-20 +|DOI:10.3389/fncel.2019.00245|https://www.sciencedirect.com/topics/medicine-and-dentistry/natural-killer-t-cell" +347 CL:0000839 CL_0000839 "Myeloid lineage restricted progenitor cells are specialized stem cells that sit at a critical juncture in hematopoiesis, the process by which new blood cells are produced. They derive from hematopoietic multipotent progenitors that can differentiate into any type of blood cell. Myeloid progenitor cells are distinguished by their ability to specifically give rise to cells of the myeloid lineage only, including red blood cells, platelets, mast cells, and different types of white blood cells such as neutrophils, eosinophils, basophils, and monocytes. + +The myeloid lineage restricted progenitor cells fulfil a crucial role in maintaining and regulating the body's immune response and blood composition. They accomplish this by renewing and replenishing the diverse assortment of cells in blood and immune system. Their range of differentiation is expansive, allowing them to respond to the varying needs of the body. For instance, an infection or physical injury might require an increased production of neutrophils or monocytes respectively, and the myeloid progenitor cells are primed to produce these specific cell types under the tight regulation of various growth factors and cytokines. + +Despite their potential for wide differentiation, the commitment of these progenitors to particular cell lineages is highly controled and irreversible. Once myeloid progenitor cells progress down a particular developmental path, they lose the capacity to differentiate into other cell types; unlike hematopoietic stem cells they can also no longer self-renew at this stage. Disruptions in their differentiation or proliferation process can lead to several hematological disorders, including myeloid leukemias. +" DOI:10.1111/j.1600-065X.2010.00963.x|DOI:10.1016/j.stem.2007.10.003|DOI:10.1242/dev.083147|https://www.sciencedirect.com/topics/immunology-and-microbiology/myeloid-progenitor-cell|DOI:10.1016/j.cell.2005.02.013 +348 CL:0000838 CL_0000838 "The lymphoid lineage restricted progenitor cell is the common lymphoid progenitor that gives rise to all cells in the lymphoid lineage. These progenitor cells originate from the hematopoietic stem cells (via an intermediate cell – the hematopoietic multipotent progenitor) during hematopoiesis in the bone marrow. + +Lymphoid lineage restricted progenitor cells represent a critical juncture where cells commit to form various types of immune cells - B cells (B-lymphocytes), T cells (T-lymphocytes), natural killer cells (NK cells), and innate lymphoid cells. By providing continual renewal of the body's immune cells, these progenitor cells are essential for maintaining immunological responsiveness and defense. + +Once lineage restriction is 'triggered', common lymphoid progenitor cells have multiple lymphoid lineage potentials (and residual myeloid potential) but have lost the capacity to self-renew. Various stimulatory and inhibitory signals, such as specific cytokines and the cellular environment, guide these progenitor cells down specific lymphoid pathways, resulting in the formation of a diverse array of mature immune cells. + +The progeny of these cells determine the body's capacity to respond to varied pathogens and diseases: B cells secrete antibodies to neutralize pathogens, T cells coordinate immune response and kill infected cells, natural killer cells deal with virally infected cells and tumors, and innate lymphoid cells are involved in the early defense against pathogens and the regulation of tissue homeostasis. Lymphoid lineage restricted progenitor cells therefore play an indispensable role in the body's immune system. +" DOI:10.1242/dev.124.10.1929|DOI:10.1016/j.stem.2007.10.003|DOI:10.1111/j.1600-065X.2010.00963.x|DOI:10.1242/dev.083147 +349 CL:0000837 CL_0000837 "The hematopoietic multipotent progenitor cell is a type of stem cell found primarily in the bone marrow, which is a critical component of the body's hematopoietic system - the complex process involved in blood cell production. These cells maintain the remarkable capability to differentiate into a multitude of different blood cell types needed by the body, including erythrocytes (red blood cells), leukocytes (white blood cells), and thrombocytes (platelets), possessing what is termed as 'multipotency'. They are crucial in maintaining life-long hematopoiesis, ensuring that a constant flurry of diverse blood cells is distributed into circulation. + +Functionally, hematopoietic multipotent progenitor cells act as a critical bridge in the complex hierarchy of the hematopoietic system. Stemming from the hematopoietic stem cell, multipotent progenitors are though to emerge in the middle of this hierarchy, poised to commit to the production of specific blood cell types: While hematopoietic stem cells have long-term self-renewal capacity, multipotent progenitors appear to have low self-renewal capacity and will differentiate into myeloid or lymphoid lineages, depending on the signals they receive. These multipotent progenitors can be considered as transitional entities that response to the body's demands for different types of blood cells. + +Owing to their significant differentiation potential, hematopoietic multipotent progenitor cells play a critical role in immune response and tissue regeneration. When significant blood loss occurs or in hematological disorders, these cells can ramp up the production of specific blood cells to meet increased demand or to replace unhealthy cells. Moreover, they are heavily implicated in bone marrow transplantations where they help restore healthy blood cell production in patients with compromised hematopoietic systems. +" DOI:10.1016/j.stem.2007.10.003|DOI:10.1016/j.stem.2013.08.012|DOI:10.15283/ijsc19127|DOI:10.1038/nature13824|DOI:10.1242/dev.124.10.1929 +350 CL:0000836 CL_0000836 "The promyelocyte is a precursor cell for granulocytes; it is generated from a myeloblast during the process of hematopoiesis - the formation of blood cellular components. These cells are typically found in the bone marrow, where they undergo several stages of maturation before entering the bloodstream. Promyelocytes are larger in size than myeloblasts due to more abundant cytoplasm and have distinctive morphological features including the presence of both primary (azurophilic) granules and distinctive nucleus. + +The primary function of promyelocytes is to differentiate and mature into myelocytes, in a specific part of the hematopoiesis called granulopoiesis. Myelocytes subsequently become granulocytes, the group of white blood cells that includes basophils, eosinophils, neutrophils and mast cells. Granulocytes are crucial to the immune system's function, defending the body against infectious disease and foreign materials. Thus, the main functional role of a promyelocyte is to serve as a key stepping-stone in the production of these essential immune cells. Importantly, the promyelocyte is the last stage of cell in the granulocyte series that can undergo cell division, providing a crucial point of control in the regulation of immune cell numbers. + +Rapid or uncontroled proliferation of these cells can lead to a type of cancer known as acute promyelocytic leukemia (APL). APL is characterized by a build-up of abnormal promyelocytes in the bone marrow, which interferes with the production of normal blood cells. Likewise, deficiencies or mutations in the genes that guide the transition from promyelocyte to myelocyte can also lead to hematological diseases. +" "DOI:10.1038/nrc2943|DOI:10.1016/j.immuni.2010.11.011 +|https://www.sciencedirect.com/topics/medicine-and-dentistry/promyelocyte|https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/granulopoiesis" +351 CL:0000841 CL_0000841 "A mature conventional dendritic cell (cDC) is a specialized subtype of antigen-presenting cell. An immature cDC which has encountered signals indicative of disturbed homeostasis, infection, or host tissue damage will undergo an activation process resulting in a mature cDC with unregulated expression of major histocompatibility complex (MHC) molecules), costimulatory molecules, and cytokine production. + +The predominant function of mature conventional dendritic cells revolves around the recognition, capture, and presentation of antigens to T cells, thereby triggering and modulating the immune responses. They act as essential links between the innate and adaptive immune system, ensuring a tailored immune response to a specific pathogen. cDCs are particularly effective at cross-presentation of antigen, presenting captured antigen in the context of MHC II molecules, thereby activating CD8+ T cells. These cells are therefore important in orchestrating antitumor and antiviral immunity." DOI:10.3389/fimmu.2018.03176|DOI:10.1016/bs.ircmb.2019.07.004|DOI:10.1146/annurev-immunol-061020-053707|DOI:10.3389/fimmu.2018.03176 +352 CL:0000842 CL_0000842 Mononuclear cells refer to blood cells that have a single, round nucleus, including lymphocytes (T cells, B cells, and innate lymphoid cells) and monocytes. These are differentiated histologically from granulocytes (neutrophils, basophils, and eosinophils), which possess multi-lobed nuclei and many cytoplasmic granules. Each subtype of cell plays different roles in the immune system, responding to foreign antigens, injury, and disease. These cells can be found in the peripheral blood, lymph, and tissues, although their count may increase in the bloodstream during infection or inflammation. Mononuclear cells are generally derived from hematopoietic stem cells located in the bone marrow. https://www.ncbi.nlm.nih.gov/books/NBK563148/|https://www.ncbi.nlm.nih.gov/books/NBK500157/|DOI:10.3389/fmolb.2017.00096|https://www.sciencedirect.com/topics/medicine-and-dentistry/mononuclear-cell +353 CL:0000875 CL_0000875 "Non-classical monocytes, also known as patrolling monocytes, are a subtype of monocytes in the circulation, accounting for approximately 5-10% of total human monocytes. These monocytes are characterized by the differential expression of two surface markers, CD14 and CD16, with non-classical monocytes expressing CD14 and high levels of CD16 (CD14+ CD16++). Classical monocytes are released from the bone marrow into the circulation and can transition to intermediate followed by non-classical monocytes. + +Non-classical monocytes patrol the endothelium and, upon sensing inflammation or injury, migrate across it. Non-classical monocytes are also involved in the removal of damaged cells via phagocytosis. This process enables the cells to engulf and destroy pathogens, debris, and apoptotic cells. During homeostasis, these monocytes appear to have an important function in maintaining vascular integrity. + +Non-classical monocytes are also able to induce CD4+ T cell proliferation and sense viruses. They can produce and secrete a wide range of inflammatory cytokines and chemokines to reinforce and shape the immune response. Non-classical monocytes also appear to play a role in different inflammatory diseases states including atherosclerosis, multiple sclerosis, and rheumatoid arthritis." DOI:10.1146/annurev-immunol-042617-053119|DOI:10.1016/j.immuni.2018.10.005|DOI:10.1111/sji.12883 +354 CL:0000915 CL_0000915 "The CD8-alpha-alpha-positive, alpha-beta intraepithelial T cell, often abbreviated as CD8αα IEL, is a specialized immune cell found within the epithelial layer of mucosal surfaces, such as the intestines. CD8αα IEL have been studied extensively in mice, but equivalent cells are thought to be present in humans, albeit at lower numbers. + +These cells represent a subset of intraepithelial T lymphocytes characterized by the expression of both CD8-alpha-alpha homodimer and the alpha-beta variant of the T cell receptor (TCR). Other features shared with intraepithelial T lymphocytes include the expression of T-bet, a master transcription factor that controls expression of proinflammatory cytokines, natural killer cell receptors, and an activated phenotype (high expression of CD69). + +Functionally, CD8αα IELs are thought to play a role in maintaining epithelial integrity, local immune surveillance, and protection against microbial pathogens. Upon detecting alterations associated with infection or inflammation, these cells orchestrate immune responses to restore tissue homeostasis, primarily through the secretion of cytokines and chemokines, and directly eliminating infected cells. + +CD8αα IELs have been shown require β2 microglobulin-dependent MHC class I expression for their generation and/or homeostasis. They share some characteristics with natural killer cells and might have similar suppressive and regulatory roles which they perform through the production of IL-10 and TGFβ. For example, they have been shown the prevent induced colitis, indicating that by modulating immune responses, CD8αα IELs prevent excessive and damaging immune activation that can lead to chronic inflammatory conditions or autoimmunity. +" DOI:10.1016/j.coi.2019.04.010|DOI:10.3389/fimmu.2022.1059042|DOI:10.1093/cei/uxad049|DOI:10.1111/j.1600-065X.2006.00488.x +355 CL:0000990 CL_0000990 "Conventional dendritic cells (cDCs) are primarily responsible for processing antigens and presenting them to T cells to initiate an immune response. Also known as classical dendritic cells, cDCs originate from hematopoietic stem cells in the bone marrow, maturing in peripheral tissues. They are characterized by their distinct morphology, which features a central body with numerous branching extensions known as dendrites. + +These cells have a pivotal role in adaptive immunity, bridging the gap between the innate and adaptive immune responses. They achieve this by capturing, processing, and presenting antigens to naive T-cells in the secondary lymphoid organs. This antigen presentation, in conjunction with co-stimulatory signals provided by the cDCs, instructs the T cells whether to mount an immune response against the antigen. cDCs are also very effective in the cross-presentation of antigens in the context of major histocompatibility complex (MHC) I, thereby activating CD8+ T cells an initiating a cytotoxic T cell response. + +In addition to their role in antigen presentation, cDCs have other important functions in maintaining immune homeostasis. They can perceive signals from the surrounding tissue microenvironment, responding to inflammation, and influencing or even polarizing T cell differentiation into various effector subtypes. Importantly, while cDCs are often associated with immunogenic responses, they also play a crucial role in immune tolerance, particularly towards self-antigens, thereby preventing autoimmune reactions. In conclusion, conventional dendritic cells serve as the sentinels of the immune system, monitoring for threat signals and coordinating the appropriate immune response." DOI:10.1016/bs.ircmb.2019.07.004|DOI:10.1146/annurev-immunol-061020-053707|DOI:10.3389/fimmu.2018.03176 +356 CL:0000988 CL_0000988 "Hematopoietic cells are all cells in the body that are of a hematopoietic lineage. All hematopoietic cells are derived from hematopoietic stem cells, which are the multipotent cells that are able to differentiate into either myeloid or lymphoid progenitor cells, which further develop into specific blood cell types. Throughout life, the large number of different types of cells in the blood are constantly regenerated from hematopoietic stem cells through a series of progenitor stages; blood cell formation (hematopoiesis) primarily takes place in the bone marrow. + +There are many types of specialized cells within the hematopoietic system, each with characteristic features and specific functions: + +Erythrocytes are red blood cells responsible for transporting oxygen from the lungs to the rest of the body tissues and returning carbon dioxide from the tissues to the lungs for exhalation. Granulocytes have a variety of functions including the phagocytosis of bacteria and fungi, critical in the early stages of inflammation (neutrophils), defense against parasites (eosinophils) and release of histamine and other mediators involved in inflammation (basophils). The blood also contains platelets, which are involved in blood clotting and wound healing. They adhere to damaged areas of blood vessels, release clotting factors, and aggregate to form a plug that stops bleeding. + +Myeloid cells include a large variety of specialized immune cell types that originate from hematopoietic precursors. This group includes monocytes, which are involved in phagocytosis, antigen presentation, and immune regulation, macrophages, which have many different functions in tissue homeostasis and inflammation, and dendritic cells, which are antigen-presenting cells that capture, process, and present antigens to T cells, initiating adaptive immune responses. + +Another important group of hematopoietic cells are leukocytes, which include T lymphocytes, which play a central role in cell-mediated immunity, including the activation of other immune cells and direct destruction of infected or abnormal cells, B cells, which produce antibodies recognizing and neutralizing pathogens, and natural killer cells, which target virus-infected and cancerous cells. +" DOI:10.1242/dev.201609|https://www.ncbi.nlm.nih.gov/books/NBK563148|https://www.ncbi.nlm.nih.gov/books/NBK539702/|DOI:10.1101/cshperspect.a008250 +357 CL:0001066 CL_0001066 "Erythroid progenitor cells serve as precursors for mature erythrocytes. These cells sit at a critical juncture in the erythroid lineage, representing the stage of commitment to producing red blood cells. As such, erythroid progenitor cells are a central element in hematopoiesis, the process by which the body replenishes its supply of blood cells. This production occurs primarily in the bone marrow, where erythroid progenitor cells multiply and differentiate into mature erythrocytes. + +Hematopoietic stem cells give rise to the multipotent progenitor (MPP), followed by the common myeloid progenitor (CMP), which further commits to the megakaryocyte-erythroid progenitor (MEP). Commitment to the erythroid lineage proceeds with the burst-forming unit-erythroid (BFU-E), which further differentiates into the colony-forming unit-erythroid (CFU-E), also referred to as the erythroid progenitor cell. + +Erythroid progenitor cells embark on a journey of progressive maturation marked by cellular changes such as reduced cell size, increased cell density, condensed chromatin structure, and hemoglobin accumulation. The final stages of this maturation process leads to loss of the cell nucleus and the acquisition of the characteristic biconcave shape. This process is tightly regulated through a combination of various growth factors, cytokines, and hormones, the most critical of which is erythropoietin. Aberrations in the differentiation and maturation of these progenitor cells can result in blood diseases such as anemia and polycythemia. " DOI:10.1097/MOH.0000000000000328|DOI:10.1083/jcb.96.2.386|DOI:10.1016/B978-0-323-04404-2.10002-8|DOI:10.1002/stem.2834 +358 CL:0001067 CL_0001067 "Group 1 Innate lymphoid cells (ILC1s) are one of five subsets of innate lymphoid cells (ILCs). ILC1s are largely tissue-resident cells and express the transcription factor T-bet and predominantly produce the cytokine interferon-gamma (IFN-γ). ILC1s initially included natural killer (NK) cells and T-bet+ ILC1s, but a 2018 update to the nomenclature proposed to further separate these two cell types based upon differences in development and function. However, it can be difficult to distinguish between these cell types. + +ILC1s are non-cytotoxic or weakly cytotoxic, expressing relatively low levels of perforin, and play an important role in the response to viruses, certain intracellular bacteria and parasites, and fungi. Their release of IFN-γ and tumor necrosis factor (TNF) further shapes the adaptive immune response. Their functionality mirrors Th1 helper cells. + +While ILC1s have been shown to be important in the response to infections, ILC1s have also been demonstrated to accumulate in inflammatory diseases such as Crohn’s disease, chronic obstructive pulmonary disease, and rheumatoid arthritis. " DOI:10.1101/cshperspect.a030304|DOI:10.1038/nature14189|DOI:10.1016/j.cell.2018.07.017|DOI:10.1002/eji.201747294|DOI:10.1038/nri.2017.86 +359 CL:0001071 CL_0001071 "Group 3 innate lymphoid cells (ILC3) belong to the family of innate lymphoid cells. They share a high degree of similarity with T lymphocytes, particularly in terms of their transcriptional program and their cytokine production profiles, but lack the antigen-specific receptors that characterize adaptive immune cells. Originating from common lymphoid progenitors, ILC3s are typically found in mucosal tissues and are especially prevalent in the gastrointestinal tract. The grouping of ILC3s originally included lymphoid tissue inducer (LTi) cells, which have more recently been categorized separately. + +ILC3s play an important homeostatic role in the gastrointestinal tract, contributing to mucosal barrier integrity, lymphoid organogenesis, and controlling the balance between tolerance and immunity to commensal and pathogenic bacteria, respectively. The protective role of ILC3s primarily stems from their capacity to respond to signals of microbial invasion or tissue damage, releasing an array of cytokines such as Interleukin-22 (IL-22) and Interleukin-17 (IL-17) which are dependent upon the RORγt transcription factor. These cytokines in turn mediate protective responses including the enhancement of epithelial barrier function, the promotion of tissue repair, and the control of bacterial infection. + +However, ILC3s can also contribute to the development of inflammatory diseases such as inflammatory bowel disease (IBD) and psoriasis. Therefore, studies have also emphasized the importance of regulatory mechanisms controlling ILC3 activation, providing novel insights into the complexity of immune regulation in maintaining tissue homeostasis. " DOI:10.1101/cshperspect.a030304|DOI:10.1038/nature14189|DOI:10.1016/j.cell.2018.07.017|DOI:10.1002/eji.201747294|DOI:10.1038/nri.2017.86 +360 CL:0001082 CL_0001082 "The immature innate lymphoid cell (ILC) refers to a stage in the development of the innate lymphoid cell, a type of immune cell that plays a pivotal role in the innate immune response. These cells are derived from common lymphoid progenitors and are primarily found in the bone marrow. During their immature stage, they possess the potential to differentiate into various mature innate lymphoid cell subsets that contribute to immune responses. + +Immature Innate Lymphoid Cells are characterized by their lack of antigen specificity, which distinguishes them from adaptive immune cells such as B and T lymphocytes. While they do not have antigen-specific receptors, they are programmed to respond to certain groups of pathogens or cytokine signaling. Immature ILCs display limited effector functions; however, they are critical in the development of effective innate immune responses as they give rise to the diverse array of mature ILC subsets. + +The ILC precursors develop from the fetal liver and the adult bone marrow and, depending upon the transcription factors involved, will give rise to unipotent ILC precursors which then give rise to mature ILC subsets. ILC subsets consist of natural killer (NK), ILC1, ILC2, ILC3, and lymphoid tissue inducer (LTi) cells, each having unique functions in immunity." DOI:10.1101/cshperspect.a030304|DOI:10.1038/nature14189|DOI:10.1016/j.cell.2018.07.017|DOI:10.1002/eji.201747294|DOI:10.1038/nri.2017.86 +361 CL:0001069 CL_0001069 "Group 2 innate lymphoid cells, also known as ILC2 cells, are a subset of the innate lymphoid cell family - a family of immune cells crucial for host defense, immune regulation, and tissue repair especially in the context of infections and inflammatory conditions. These cells are largely tissue-resident, predominantly residing in barrier tissues such as the skin, lungs, and gastrointestinal tract. ILC2s are defined by their expression and reliance on the GATA3 transcription factor. + +ILC2 cells play a significant role in the immune response, especially against parasitic infections and in allergic responses and autoimmune disorders. They predominantly produce type 2 cytokines including interleukin-5 (IL-5) and interleukin-13 (IL-13) in response to stimuli such as cytokines IL-25 and IL-33, which are often produced by epithelial cells in response to tissue damage. IL-5 is crucial for eosinophil activation, a component of the immune system that plays a key role in combating parasitic infections. Concurrently, IL-13 helps in expelling parasites from the body's system, as well as enforcing barrier integrity. + +ILC2s are also instrumental in tissue repair and homeostasis. They help in maintaining body metabolism and fat storage, largely by producing a hormone known as methionine-enkephalin peptides. ILC2 cells also aid in early tissue repair processes, by the secretion of amphiregulin, a growth factor. Despite their protective functions, ILC2 cells can also contribute to pathologies such as asthma and other inflammatory diseases if their actions are not properly regulated." DOI:10.1101/cshperspect.a030304|DOI:10.1038/nature14189|DOI:10.1016/j.cell.2018.07.017|DOI:10.1002/eji.201747294|DOI:10.1038/nri.2017.86 +362 CL:0002010 CL_0002010 "The pre-conventional dendritic cell (pre-cDC) are precursors of mature dendritic cells. They develop from common DC precursors in the bone marrow and exist in a semi-differentiated state. The term 'pre-conventional' denotes the stage of development of these cells prior to their maturation into conventional dendritic cells, which are critical players in immune responses. + +After leaving the bone marrow, pre-cDCs transiently circulate in the bloodstream to colonize lymphoid and non-lymphoid tissues, including skin, mucosa, spleen, and lymph nodes where they differentiate into immature conventional dendritic cells, which undergo further differentiation. In mouse and humans, the population of pre-cDCs has been shown to be heterogeneous with two subpopulations that pre-committed to differentiate into different subsets of dendritic cells (cDC1 and cDC2). + +These subsets of differentiated dendritic cells play a key role in the immune response by bringing about the regulation and initiation of T cell responses, thereby shaping the adaptive immunity. One subset is thought to be specialized in highly efficient activation of CD8+ T cells, while the other subset presents exogeneous antigens to CD4+ T cells. + +The main function of pre-conventional dendritic cells is to constantly replenish conventional dendritic cells. In response to infection additional pre-cDCs are recruited to the site of infection to meet increased tissue demand, and this pre-DC recruitment may be necessary for effective T cell responses. The molecular signals that direct pre-cDC migration remain poorly understood but recent research suggest that it involves specific chemokine receptors expressed on pre-cDCs. +" DOI:10.1002/embj.201488027|DOI:\10.1038/s41423-021-00726-4|DOI:10.1146/annurev-immunol-061020-053707|DOI:10.1111/imm.12888|DOI:10.1084/jem.20161135 +363 CL:0002028 CL_0002028 "The basophil mast progenitor cell, also referred to as the pre-basophil and mast cell progenitor or basophil-mast cell progenitor, is a cell found in the bone marrow or the spleen. These cells can differentiate further into committed basophil progenitors and mast cell progenitors which then differentiate into their respective mature cell types. This progenitor is an important source of innate immune cells which participate in the response to parasites and allergic responses. + +Like other progenitor cells, basophil mast progenitor cells are characterized by their capacity for both self-renewal, which sustains the cell population, and differentiation, which results in the specialized basophils and mast cells. IRF8 induces expression of GATA2, a transcription factor which, together with STAT5, can induce the expression of C/EBPα or MITF, which mutually suppress the expression of the other gene. C/EBPα and MITF induce differentiation into either basophils or mast cells, respectively. + +As they differentiate into basophils and mast cells, basophil mast progenitor cells contribute significantly to the body’s immune responses. Basophils are known to combat parasitic infections and play a crucial role in severe allergic reactions like anaphylaxis, by releasing histamine and other vasoactive amines. Mast cells release a host of inflammatory mediators that further drive immune responses, while their chronic activation can lead to hypersensitivity and persistent inflammation, as seen in conditions such as asthma and eczema." DOI:10.1016/j.alit.2016.01.006|DOI:10.1007/s11882-014-0457-1 +364 CL:0002193 CL_0002193 "A myelocyte is a type of immature granulocyte found in the bone marrow during the production of blood cells, a process known as hematopoiesis. Myelocytes represent an intermediate stage in the development of granulocytes, which are a type of white blood cell essential for the immune system. The three kinds of granulocytes that derive from myelocytes are neutrophils, eosinophils, and basophils, each with distinct properties and functions. Myelocytes possess some functionalities of a mature cell such as the presence of specific granules. + +The main function of myelocytes is to differentiate into mature granulocytes. The process starts with a hematopoietic stem cell, which progressively matures into a myeloblast, and further into a promyelocyte before eventually becoming a myelocyte. At this stage, the cell begins producing granules that carry specific enzymes and other substances used to fight infections. The most common type of myelocyte is the neutrophilic myelocyte, which eventually develops into a neutrophil, the most common type of white blood cell. + +Neutrophilic myelocytes contribute significantly to the body's primary immune response as mature neutrophils are often the first cells to arrive at a site of infection. They ingest and destroy bacteria and other harmful agents to prevent further infection. Eosinophilic and basophilic myelocytes develop into eosinophils and basophils, respectively, playing their role in managing allergic reactions and parasitic infections. Dysfunction in myelocyte development can give rise to various diseases, including different forms of leukemia, where myelocytes undergo uncontrolled proliferation. +" DOI:10.1038/s41375-023-01989-8|DOI:10.1182/blood.V71.3.640.640|https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/myelocyte|https://www.sciencedirect.com/topics/medicine-and-dentistry/granulopoiesis +365 CL:0000738 CL_0000738 "Leukocytes, also commonly referred to as white blood cells (WBCs), are a key constituent of the body's immune system, principally responsible for defense against infections and diseases. They comprise approximately 1% of total blood volume in a healthy individual. They are named after their characteristic white appearance, which is caused by the lack of hemoglobin that imparts a red color to red blood cells. There are five main types of leukocytes, including lymphocytes, monocytes, neutrophils, basophils, and eosinophils, each with different functions which contribute to maintaining the body's immune response. + +Lymphocytes are the cornerstone of the adaptive immune system, responsible for immune response after infection or vaccination. They are subdivided into B cells, T cells, and innate lymphoid cells, each with their distinct roles. B cells produce antibodies, which specifically bind and neutralize foreign substances. T cells execute two key functions - helper T cells aid in the immune responses by releasing cytokines to direct the response, and cytotoxic T cells are responsible for killing infected or neoplastic cells. Natural killer cells and other innate lymphoid cells participate in the earlier innate immune response against tumor formation and response to viral infections. + +Neutrophils, the most abundant type of leukocytes, are the first responders to microbial infection. Their prime function is to ingest, neutralize, and destroy pathogens via phagocytosis. Eosinophils are vital for combating multicellular parasites and certain infections also have roles in allergic reactions. Monocytes, circulating in the bloodstream, rapidly transform into macrophages upon infection or tissue injury and start devouring foreign substances. Basophils constitute the smallest fraction of the leukocyte population and play a critical role in allergy and asthma development, and parasite infections by releasing chemical signals, such as histamine and serotonin, that recruit other leukocytes to the site of inflammation." https://www.ncbi.nlm.nih.gov/books/NBK563148/ +366 CL:0002393 CL_0002393 "Intermediate monocytes, also defined as CD14++CD16+ monocytes, constitute one of the three subsets of human monocytes which also include classical and non-classical monocytes. These cells play a crucial role in the physiological function of the immune system and are particularly significant in the human body's response to inflammation and infection. With a diverse array of functions, intermediate monocytes uniquely contribute to the immune response potency by bridging the gap between the classical and non-classical monocyte subsets. + +Intermediate monocytes exhibit a combined functionality of the two other subsets in terms of their phenotypic characteristics, functional capabilities and gene expression profiles. They express high levels of CD14 (like classical monocytes) and also express CD16 (like non-classical monocytes). These monocytes generally release lower amounts of cytokines compared to classical and non-classical monocytes, but produce the most reactive oxygen species. Intermediate monocytes may also induce T cell proliferation and express high levels of major histocompatibility complex molecules for antigen presentation. + +The relative number of intermediate monocytes in the bloodstream increases under conditions of severe inflammation and infection, although their roles have not yet been clearly defined. Additionally, some studies reported findings on monocytes with a combined population of intermediate and non-classical monocytes, further complicating the understanding of the function of these cells." DOI:10.2147/JIR.S292513|DOI:10.1182/blood-2010-02-258558|DOI:10.1182/blood-2010-12-326355 +367 CL:0002496 CL_0002496 "Intraepithelial lymphocytes (IELs) are a large and diverse population of mainly T cells that reside within the epithelial cell layer of various mucosal tissues in the body, including the skin, intestine, and respiratory tract. These cells represent a substantial amount of the total lymphocyte pool and are most numerous in the intestine. They have distinct phenotypes and functional characteristics compared to lymphocytes residing in other tissues. + +Most intraepithelial lymphocytes express heterodimeric T-cell receptors (TCRs) consisting of αlpha and beta chains (TCRαβ), or less commonly gamma and delta chains (TCRγδ), together with the CD8 co-receptor (αβ or αα); there are also smaller subpopulations of IELs that areCD4+, or negative for both CD4 and CD8. Intraepithelial T cells typically express high levels of activation markers, tissue-homing integrins, and receptors and molecules characteristic of natural killer cells and cytotoxic T lymphocytes. TCRαβ+CD8+ IEL are able to recognize both transformed self antigens via natural killer receptors and foreign antigen via the TCR. + +The primary function of IELs is to maintain the integrity of mucosal barriers against pathogens. Given their strategic location within the epithelial layer, they are often the first immune cells that encounter invading infectious agents, such as bacteria, fungi, or viruses. Upon encountering pathogens, IELs activate and quickly respond by either directly killing the infected epithelial cells or alerting other immune cells. This rapid response, initiated by IELs, helps constrain the infection at the point of entry and is vital to maintaining the integrity of mucosal barriers. + +In addition to their central role in maintaining the integrity of epithelial barriers, IELs also play a crucial role in maintaining the physiological health of the epithelia by promoting repair and regeneration after injury. Furthermore, IELs are pivotal in supporting oral tolerance to dietary antigens and gut microbiota. An imbalance in the number and functionality of IELs is often associated with various human diseases including celiac disease, inflammatory bowel disease, metabolic syndrome, and colorectal cancer. +" "DOI:10.1038/s41385-020-0294-6 + +|DOI:10.1038/s41385-018-0016-5|https://www.sciencedirect.com/topics/immunology-and-microbiology/intraepithelial-lymphocyte|DOI:10.1038/nri3007|DOI:10.1016/j.it.2017.11.003" +368 CL:0008001 CL_0008001 "Hematopoietic precursor cells are multipotent cells that are able to differentiate into specific fully matured blood cell types. They are primarily observed in the red bone marrow, the main site of hematopoiesis in adults. + +The primary function of hematopoietic precursor cells is to maintain a constant supply of new blood cells throughout an individual's life. This is executed through a delicate balance of self-renewal and differentiation: hematopoietic stem cells can either self-replicate to produce more of the same stem cell type or develop into multipotent hematopoietic progenitor cells that differentiate further to form any of the three main types of blood cells - erythrocytes (red blood cells), leukocytes (white blood cells), and thrombocytes (platelets). Such versatility makes these cells critical in maintaining blood cell homeostasis. + +Moreover, hematopoietic precursor cells play a potent role in clinical applications, particularly in the treatment of hematological disorders. Stem cell transplantation is utilized to replace the bone marrow of patients with a healthy one, often after chemotherapy or radiation treatment for diseases such as leukemia, lymphoma, or myeloma. In these scenarios, the transplanted stem cells or precursors can rebuild the patient's blood cells and immune system. +" DOI:10.1242/dev.170571|DOI:10.1038/s41586-022-04571-x|https://www.sciencedirect.com/topics/medicine-and-dentistry/hemangioblast|DOI:10.1101/cshperspect.a008250|DOI:10.1073/pnas.0509314102 +369 CL:1001610 CL_1001610 "Bone marrow hematopoietic cells are a category of blood-forming stem cells located within the bone marrow, the soft, spongy tissue that fills the cavities of bones. The bone marrow contains specialized environments, referred to as the stem cell niche, to nurture and regulate the development of these cells. These cells are vital for the production and development of new blood cells, functioning as the primary source of cellular regeneration throughout a person's life. They are capable of self-renewal and differentiation into every type of mature blood cell. + +Hematopoietic stem cells differentiate into two main lineages: myeloid and lymphoid cells. Myeloid cells can further differentiate into red blood cells, which carry oxygen throughout the body, platelets that contribute to clot formation, and certain types of white blood cells such as neutrophils, eosinophils, basophils, and monocytes. These white blood cells play a crucial role in the innate immune response, helping to fight infection and disease. Lymphoid cells develop into other types of white blood cells: T-cells, B-cells, and innate lymphoid cells, which contribute to the cellular and humoral immune response. + +Furthermore, the bone marrow hematopoietic cells have a unique ability to replace any blood cell in the body that has been destroyed or lost due to illness or injury. Through this regenerative functionality, they are vitally important to the body's defense mechanisms, disease response, and homeostasis. These cells are used in bone marrow transplants and are of interest in regenerative medicine applications." DOI:10.1016/B978-0-323-04404-2.10002-8|DOI:10.1182/blood-2009-11-253534|DOI:10.1016/j.semcdb.2020.05.014 +370 CL:2000001 CL_2000001 Peripheral blood mononuclear cells (PBMCs) refer to a mixture of blood cells that have a round nucleus. These cells are critical components of the immune system and include lymphocytes (T cells, B cells, and natural killer cells), monocytes, and dendritic cells. PBMCs are isolated from whole blood using density gradient centrifugation, separating them from red blood cells and granulocytes. PBMCs are often used as the source of various immune cells or stem cells which may be enriched and activated or differentiated for research purposes. https://www.ncbi.nlm.nih.gov/books/NBK500157/|DOI:10.1186/scrt139|https://www.sciencedirect.com/topics/neuroscience/peripheral-blood-mononuclear-cell +371 CL:2000055 CL_2000055 "Liver dendritic cells (DCs) refer to all dendritic cells found in the liver. Liver DCs, much like other DCs, play a critical role in initiating and directing immune responses. However, they show unique characteristics and functions due to their location in the liver, an organ with an important role in metabolism and immunity. + +The liver contains both conventional or classical and plasmacytoid DCs. Liver DCs generally have an immature phenotype and are thought to aid in the maintenance of hepatic tolerance. The liver is constantly exposed to dietary and gut-derived antigens, which requires the liver to strike a balance to avoid excessive immune response against these substances. Liver dendritic cells play an essential role in this balance through various mechanisms, such as promoting the development of regulatory T cells. In some cases, liver DCs have also been demonstrated to exhibit stimulatory activity. + +Liver DCs play an important role in liver transplantation outcomes and hepatic diseases including viral infections, carcinomas, and primary biliary cirrhosis." DOI:10.1016/bs.ircmb.2019.07.004|DOI:10.1046/j.0818-9641.2001.01058.x|DOI:10.1136/gut.52.2.307|DOI:10.1016/j.bbadis.2013.01.005|DOI:10.1002/hep.21974 +372 CL:0002076 CL_0002076 "Endo-epithelial cells, also known as endothelial cells, constitute a specialized cell type forming the endothelium layer lining blood vessels, lymphatic vessels, and the heart. + +A primary function of endo-epithelial cells is the regulation of vascular permeability, controlling the passage of compounds, including gases, molecules, and cells, between the bloodstream and tissues. They facilitate inflammation by allowing white blood cell migration into tissues for infection defense and regulate blood clotting, producing factors that both inhibit and stimulate clot formation to prevent excessive bleeding or clotting. + +Endo-epithelial cells also play a role in angiogenesis, the formation of new blood vessels. In response to signals, they expand and sprout to create new vessels, addressing tissue needs for oxygen. Consequently, these cells play roles in wound healing, tumor growth, and the regulation of blood pressure, cell growth, and anti-aging processes." https://www.sciencedirect.com/topics/medicine-and-dentistry/endothelial-cell|DOI:10.3390/cells11121935|DOI:10.1007/s00281-011-0285-5|DOI:10.1161/01.RES.0000259593.07661.1e|DOI:10.5455/medarh.2018.72.444-448 +373 CL:0002251 CL_0002251 "Epithelial cells lining the alimentary canal, also known as gastrointestinal tract epithelial cells, compose the innermost layer throughout the digestive tract from mouth to anus. Their main functions include nutrient absorption, waste excretion, and forming a protective barrier against harmful pathogens to uphold overall bodily health. + +These cells display substantial adaptability depending on the specific region of the alimentary canal they are located in. For instance, in the stomach, they form gastric pits, releasing digestive enzymes and juices for food breakdown. In the small intestine, finger-like projections called villi and microvilli increase the surface area, optimizing nutrient absorption. + +Integral to the immune system as part of gut-associated lymphoid tissue (GALT), these cells identify and eliminate harmful entities, coordinating with other immune cells. They also regulate gut microbiota, maintaining a delicate balance between the host and myriad microorganisms in the intestines. In essence, these cells execute multifaceted functions crucial for normal digestive system operation." DOI:10.1155/2018/2819154|https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/small-intestine-absorption|DOI:10.1016/j.psj.2019.12.011 +374 CL:0000101 CL_0000101 "Sensory neurons, also known as afferent neurons, are a specialized type of neuron fundamental to the nervous systems of all multicellular organisms. They transform specific types of environmental stimuli, such as light, sound, heat, or pressure, into internal signals that can be interpreted by the nervous system. The primary role of sensory neurons is to serve as conduits for sensory information, transmitting messages from peripheral sensory organs (such as the skin, muscles, and internal organs) to the central nervous system (comprised of the brain and spinal cord). + +The functionality of sensory neurons depends on their ability to convert specific forms of external energy into electrical energy that can be interpreted by the brain. This process, known as transduction, typically occurs at the specialized sensory endings of the neuron that are designed to detect a particular form of stimulus. Once a stimulus is detected, the sensory neuron generates an electrical signal (an action potential) which it transmits along its axon towards the central nervous system. Different kinds of sensory neurons respond to different stimuli; for instance, photoreceptor cells in the eyes respond to light, while mechanoreceptor cells in the skin respond to touch or pressure. + +Moreover, the organization of sensory neurons plays a pivotal role in how sensory information is processed. Depending on the type of stimulus and where it’s detected, sensory neurons can have different structures. Many have long dendrites extending from the cell body, where the signal is received. The cell body contains the neuron's nucleus and is responsible for maintaining the life functions of the cell. From here, the signal travels down the axon, a long fiber that can reach lengths of up to several feet, toward the central nervous system. The specialized structure and strategic placement of these neurons allow the nervous system to accurately interpret and swiftly react to a wide array of environmental inputs, thereby ensuring the organism’s successful interaction with its environment." DOI:10.1146/annurev.neuro.29.051605.113024|DOI:10.1523/JNEUROSCI.15-12-07757.1995|DOI:10.1038/nrn2993|DOI:10.1016/j.neuron.2013.07.051|DOI:10.1023/B:NEUR.0000010080.62031.f0 +375 CL:0000104 CL_0000104 "A multipolar neuron is a specialized type of neuron that comprises one axon and multiple dendrites, distinguishing it from other varieties in the neuronal family. This cell type is distinctively known for its structural architecture and extraordinary capabilities in information processing. The multipolar configuration enables a wide branching network that supports the reception, integration, and transmission of signals over varying distances, translating into complex functionalities like thought, action, and perception. + +The primary function of a multipolar neuron is to process and transmit information in the form of electrical impulses or action potentials. Each of the multiple dendrites acts as a receiver, collecting synaptic inputs from other neurons and transferring these signals to the neuron's cell body. Here, the information is assembled and, upon reaching a particular threshold, will trigger the generation of an action potential along the axon, the singular elongated projection that results in the neuron's output. This signal propagation, facilitated by the axon's myelination and nodes of Ranvier, leads to highly efficient and fast information transmission to other neurons, muscle cells, gland cells, and other organs. + +The capacity of multipolar neurons to establish vast connections with other neurons makes them the primary constituents of the central nervous system. They play indispensable roles in both sensory and motor pathways, as well as in higher cognitive functions such as memory and learning. These neurons also enrich the autonomic system, contributing to both sympathetic and parasympathetic pathways. Hence, multipolar neurons play an essential role in performing and regulating a plethora of activities, ranging from basic reflexes to intricate cognitive processes." DOI:10.1101/cshperspect.a001644|DOI:10.1523/JNEUROSCI.1610-15.2015|DOI:10.1126/science.3059497|DOI:10.1016/j.autneu.2006.05.003 +376 CL:0000120 CL_0000120 "Granule cells are a class of small neurons found significantly in the cerebellum, olfactory bulb, and the dentate gyrus of the hippocampus in the human central nervous system. Their name derives from the presence of internal granular structures and they are one of the most abundant cell types in the entire brain, with estimates suggesting they likely comprise over half of all neurons. Due to their location, these cells play a vital role in the modulation of motor coordination, the olfactory system, and some aspects of memory and learning. + +Structurally, granule cells differ depending on their location. They have unmyelinated, very thin, T-shaped axons and a few short dendrites in the cerebellum. These dendrites receive information from a variety of sources, while their axons transmit the information to other parts of the brain. In granule cells of the cerebellum, the axons form parallel fibers that run into the molecular layer and synapse onto Purkinje cells, stellate, and basket cells, setting up a neuronal circuit critical for generating precise and fluid movements. + +Functionally, granule cells receive excitatory input from mossy fibers, which deliver sensory and motor information to the cerebellum, and this interaction is fundamental for the timing and coordination of body movements. In the olfactory bulb, granule cells process and modify olfactory information before passing it to the cerebral cortex, thereby aiding smell perception. Meanwhile, in the hippocampus, these cells participate in the formation and sorting of memories, particularly episodic memories. Due to their number, location, and function, the granule cells have a significant influence on cognition and behavior. +" DOI:10.3389/fncir.2020.611841|DOI:10.1016/j.brainresrev.2007.03.005|DOI:10.1016/j.neubiorev.2016.02.021|DOI:10.1016/S0168-0102(97)00099-0|DOI:10.12688/f1000research.15021.1 +377 CL:0000006 CL_0000006 "Neuronal receptor cells, also referred to as sensory neurons or receptor neurons, are specialized types of neurons responsible for converting external stimuli into internal electrical signals. This type of neuron forms the foundation of our five integral senses: touch, taste, smell, sight, and sound. They are particularly crucial as they help organisms interpret their surroundings and react accordingly to adapt for survival. These cells are typically composed of dendrites, an axon, a cell body and a synaptic terminal, with the attributes and responses varying according to the type of physical stimuli they are designed to receive. + +The function of neuronal receptor cells is rooted in their ability to transduce or convert various stimuli, ranging from heat, light, sound waves, chemical substances to mechanical pressure, into electrical signals. These signals are then carried via electrical impulses to the brain or spinal cord where they are interpreted as sensory information. Each receptor cell is usually specialized towards a specific type of stimulus. For example, photoreceptor cells in the retina of our eyes can convert visible light into electrical signals, while mechanoreceptor cells in our skin translate mechanical pressure or vibration. + +The specialized nature of neuronal receptor cells contributes significantly to their role in maintaining homeostasis and enabling interaction with the environment. The responses generated from these cells can lead to various physiological reactions like muscle contraction, glandular secretion or changes in the nervous system to help the body adapt and react appropriately to its surroundings. These cells help organisms make sense of the world around them, from feeling the warmth of the sun to hearing a melodious tune. Thus, neuronal receptor cells form a critical pathway in the perception of our external world, making our everyday interaction with the environment possible and meaningful." DOI:10.1146/annurev.neuro.29.051605.113024|DOI:10.1523/JNEUROSCI.15-12-07757.1995|DOI:10.1038/nrn2993|DOI:10.1016/j.neuron.2013.07.051|DOI:10.1023/B:NEUR.0000010080.62031.f0 +378 CL:0000100 CL_0000100 "Motor neurons, also known as motoneurons, are a type of neural cell that is fundamental to voluntary movement of muscles. Located within the central nervous system (CNS), motor neurons in the motor cortex travel to the brainstem and spinal cord. Motor neurons in the brainstem and spinal cord extend their lengthy axons out to muscles throughout the body. These specialized neurons are an inherent part of the so-called somatic division of the nervous system which mediates conscious control of skeletal muscles. + +The primary function of motor neurons is to relay signals from the CNS to the body's many muscles, controlling both their contraction and relaxation. In response to impulses transmitted from the brain or spinal cord, it creates an electrical signal (action potential), which travels along its axon to cause the controlled movement of specific muscles. Motor neurons can connect with skeletal muscles, cardiac muscles, or glands, leading to three respective types: somatic motor neurons, autonomic motor neurons, and the neurons of the enteric nervous system. + +Key components of motor neurons include the cell body (soma), dendrites, and axons. The cell body houses the nucleus and is the site of the neuron's intrinsic functions. Dendrites are thin structures that branch from the cell body and receive messages (electrical signals) from other neurons. The axon, a long, single tail-like extension, carries these signals away from the cell body towards the targeted muscle. If a motor neuron is damaged or dies, the muscle or gland it controls can lose function, which can result in conditions like motor neuron disease, leading to muscle weakness and atrophy." DOI:10.1016/j.semcdb.2017.11.016|DOI:10.3389/fncel.2014.00293|DOI:10.1249/JES.0000000000000032|DOI:10.1146/annurev.neuro.051508.135722 +379 CL:0000119 CL_0000119 "Cerebellar Golgi cells are a specific type of inhibitory interneuron found within the granular layer of the cerebellum, a major part of the vertebrate brain responsible for motor control, learning, and cognitive functions. Named after the Italian scientist Camillo Golgi, these cells play a unique and important role in modulating electrical signals in the complex cerebellar neural network. + +The distinctive feature of the cerebellar Golgi cells is their dendritic arbor that extends throughout the molecular layer of the cerebellum, in line with the axons of the granule cells. The axons of Golgi cells primarily synapse with the dendrites of granule cells, generating a synaptic feedback loop that plays a vital role in regulating the intensity and timing of signal transmission. They also form synapses with mossy fiber terminals, which provide primary input to the cerebellar cortex. + +Functionally, cerebellar Golgi cells serve as ""gatekeepers"" of the cerebellar cortex. They have a strong inhibitory influence on granule cells, modulating the information flow to the Purkinje cells, the main output neurons of the cerebellar cortex. Thus, Golgi cells play a critical role in controlling the input-output relationship within the cerebellum, shaping the timing and strength of signals originating from various sensory and motor areas of the cerebral cortex. This regulatory function is instrumental for the fine-tuning of motor coordination, timing and learning. Thus, alterations in Golgi cell functions can contribute to a range of neurological and neuropsychiatric disorders such as ataxias and cognitive deficits." DOI:10.1113/jphysiol.2010.189605|DOI:10.1126/science.1215101|DOI:10.3389/fncir.2013.00093|DOI:10.1016/j.neuron.2011.10.030|DOI:10.1016/S0896-6273(00)81126-5 +380 CL:0000122 CL_0000122 "Stellate neurons are a specialized type of interneurons found predominantly in the cerebral cortex and the cerebellum, two major components of the brain's central nervous system. These neurons are named for their distinct star-like shape, characterized by short dendrites that radiate from the cell body in multiple directions. They are a key component of the mammalian neural circuit due to their unique morphology and crucial functions in neural communication. + +Stellate neurons play a pivotal role in the processing and transmission of information within the brain. In the cerebellum, these neurons are predominantly inhibitory and release the neurotransmitter gamma-aminobutyric acid (GABA), effectively regulating the excitability of other neurons within the network and thus fine-tuning the neuron-to-neuron communication. Their extensive dendritic network allows for connections with multiple neurons allowing for the integration of synaptic inputs from various sources in the brain. This widespread connectivity places stellate neurons at the heart of information processing in the central nervous system. + +In addition to their important inhibitory role in regulating and processing information, the role of stellate neurons in the cerebellum differs slightly from their cortical counterparts. The cortical spiny stellate neurons are excitatory and release the neurotransmitter glutamate. They are involved in motor control and responsible for coordinating precise, voluntary movements and maintaining posture and balance. Any dysfunction in these cerebellar neurons can lead to movement disorders, highlighting their significance in our daily activities. " DOI:10.1002/cne.901460304|DOI:10.1126/science.aai8178|DOI:10.1523/JNEUROSCI.2929-06.2006|DOI:10.1038/nn1698|DOI:10.1007/s11055-006-0093-x +381 CL:0000210 CL_0000210 "Photoreceptor cells are specialized types of neurons found in the retina, responsible for the vital task of converting light into signals that can stimulate a visual response. These cells are called photoreceptor cells because they are light-sensitive, enabling vision in conditions ranging from extremely dim to very bright light. There are two main types of photoreceptor cells in the human eye: rods, which are highly sensitive to light and allow for vision in low-light conditions, and cones, which are responsible for color vision and function best in bright light. + +The photoreceptor cells function by absorbing light rays and converting them into electrical signals. These signals are then sent to the brain via the optic nerve and are interpreted as visual images. This process begins when the photopigment (a light-sensitive compound) found in photoreceptor cells absorbs light, which triggers a chemical reaction. This reaction leads to changes in the photopigment's configuration and, consequently, alters its electrical properties. This change initiates a signal that is transmitted through the cell and onwards to connecting neurons. + +Furthermore, photoreceptor cells exhibit a unique and highly specialized structure that reflects their function. Rods, named because of their elongated, rod-shaped structure, consist of an outer segment filled with disks containing rhodopsin, the photopigment responsible for detecting light. Cones, on the other hand, are more conical and have three different types of photopigments, each one sensitive to a different range of wavelengths, allowing for the perception of color. Given the importance of photoreceptor cells in vision, damage or degeneration to these cells can lead to vision impairment or blindness, highlighting their key role in visual perception." DOI:10.1242/jcs.175687|DOI:10.1016/j.cbpa.2008.04.600|DOI:10.1113/JP282058|DOI:10.1016/j.neubiorev.2017.12.006|DOI:10.1038/nrg2717 +382 CL:0000287 CL_0000287 "Eye photoreceptor cells, also commonly known as photoreceptors, are specialized types of cells found in the retina, the light-sensitive layer at the back of the eye. They are integral to the complex process of vision, as they are directly involved in converting light into electrical signals. This process is known as phototransduction. There are two primary classes of photoreceptor cells; rods, which function mainly in dim light and provide black-and-white vision, and cones, which function in brighter light and allow for the perception of color. + +Rods and cones carry out their roles through sophisticated biochemical reactions. The main component of these reactions is a protein called opsin, which binds to a small molecule known as retinal. In the presence of light, retinal changes its shape, leading to a series of chemical reactions that result in changes to the cell’s electrical potential, thus creating an electrical signal that travels to the optic nerve. Rod cells possess only one kind of opsin, called rhodopsin, which only allows them to distinguish between light and dark. Conversely, cone cells have three types of opsins, allowing for the differentiation of various colors. + +The spatial distribution of these cell types throughout the retina also contributes to their function. Rod cells are more numerous and are distributed more at the periphery of the retina, contributing to peripheral and night vision. On the other hand, cone cells are concentrated in the macula, a tiny central region in the retina, and with the highest density in the fovea, a small pit in the macula. This distribution of cones lies at the base of fine detail and color vision in the central visual field. In summary, eye photoreceptor cells carry out the primary function of transforming light into visual signals, a role that is crucial for the overall process of vision." DOI:10.1098/rstb.2009.0051|DOI:10.1186/gb-2005-6-3-213|DOI:10.1146/annurev.biophys.31.082901.134348|DOI:10.1002/cne.902920402|DOI:10.1038/eye.2016.107 +383 CL:0000402 CL_0000402 "Central Nervous System (CNS) interneurons are one of the three major neuron types found within the nervous system and primarily present in the brain and spinal cord. They have a crucial role in transmitting signals between the other two major neuron types: sensory neurons and motor neurons. Unlike sensory and motor neurons, CNS interneurons are confined within the CNS and do not extend to peripheral body parts. In the structure of the neural circuit, these interneurons correspond to a middle link connecting input and output neurons. + +CNS interneurons are incredibly diverse, both in form and function, characterized by distinct morphology, physiology, connectivity, and patterns of gene expression. Interneurons are typically multipolar, having many dendritic projections that collect information from a wider range of input neurons, and one axon to relay the processed information. They participate in creating complex functional circuits, contributing to different types of inhibitory and excitatory signaling phenomenons. The precise balance of excitation and inhibition managed by these interneurons is essential for the proper functioning of neural circuits. + +Functionally, CNS interneurons play critical roles in reflexes and neural processing activities, including interpretative functions of the brain such as sensory perception, motor control, and learning and memory functions. Through their influence over motor neurons, interneurons help regulate and coordinate body movements, including complex sequences and rhythmic patterns. Additionally, these cells play a key role in higher brain functions such as cognition by contributing to the understanding coming from the sensory organs. Abnormalities or malfunctions in interneurons can be associated with various neurological disorders, including epilepsy, schizophrenia, and autism." DOI:10.1038/nature12983|DOI:10.1038/nrn.2017.30|DOI:10.1016/j.tins.2003.12.008|DOI:10.1016/j.tins.2018.07.015|DOI:10.1038/nrn3155 +384 CL:0000397 CL_0000397 "Ganglion interneurons, sometimes classified under 'relay neurons,' are complex cellular structures prominently found in the nervous system across various organisms. These cells serve as intermediaries or connectors, conducting impulses between afferent (or sensory) neurons and efferent (or motor) neurons within the body. They have specialized roles in sensory-motor integration within the nervous system and play a pivotal part in defining the complexity and precision of the nervous system. + +These highly specialized neurons are predominantly located in the spinal cord and brain, particularly abundant in the gray matter of these regions, forming complex neural networks. The increased presence of glial cells around interneurons acts as an insulator enhancing the speed of impulse transmission. Ganglion interneurons receive informational input through dendrites from sensory neurons; this information is then converted into electrical impulses, which are processed and transmitted to other neurons or effectors, such as muscles or glands, through axons. + +Furthermore, these ganglion interneurons have significant roles in the formulation and execution of motor reflexes and serve as integral components of reflex arcs. They also participate in the modulation and filtration of relevant sensory information, ensuring that signals reaching the late-stage processing units (like the brain) are refined and critical to the organism's survival. Consequently, these neurons significantly influence the organism's behavior based on the incoming sensory information. Overall, they are responsible for creating connections amongst various neural circuits, making them pivotal in producing integrated responses and maintaining the proper functioning of the nervous system." DOI:10.1038/nn.2707|DOI:10.1523/JNEUROSCI.5570-03.2004|DOI:10.1371/journal.pcbi.1002626|DOI:10.1152/jn.1992.68.4.1384|DOI:10.1111/j.1748-1716.1962.tb02497.x +385 CL:0000498 CL_0000498 "Inhibitory interneurons, often referred to as local circuit neurons, are integral components of the central nervous system where they play key roles in refining neural circuits and shaping network activity. Known for their inhibitory nature, these neurons form connections mainly within the same region of the brain or spinal cord where they are located. This localization allows them to impact the activities of nearby excitatory neurons by means of inhibitory networks to inhibit or reduce the likelihood of the firing of these excitatory neurons. + +Functionally, Inhibitory Interneurons serve as primary regulators and modulators of the output of nerve cells, orchestrating a balance between excitatory and inhibitory activities in neural networks. It is through their characteristic release of inhibitory neurotransmitters, such as gamma-aminobutyric acid (GABA) and glycine, that they manage to suppress postsynaptic potentials, preventing or reducing the propagation of action potentials. This regulation is not only essential for maintaining equilibrium within the nervous system, but also helps prevent conditions that arise from excessive neuronal activities, such as epilepsy. + +Inhibitory Interneurons, while relatively small in number compared to their excitatory counterparts, exhibit considerable diversity in their structure, function, and neurochemical expression. They are broadly categorized into multiple subtypes, each with its unique influence on neural circuit behavior and role in different behaviors or cognitive processes. For instance, certain subtypes are involved with timing and synchrony of neural activity, while others participate in contrast enhancement in sensory processing or in isolating specific activity patterns. " DOI:10.1152/physrev.00007.2017|DOI:10.1016/j.neuropharm.2014.09.011|DOI:10.1007/s12576-016-0442-7|DOI:10.1523/JNEUROSCI.23-02-00622.2003|DOI:10.1038/nature25999 +386 CL:0000526 CL_0000526 "An afferent neuron, also known as a sensory neuron, is an essential cell type that plays a critical role in the sensory pathway of the nervous system. These neurons are responsible for transmitting signals from sensory receptors, including those in the skin, eyes, ears, tongue, and nose, towards the central nervous system. Afferent neurons work primarily to convert external stimulus information, whether it be light, sound, physical touch, or smell, into internal electrical signals - a process is known as sensory transduction. + +The structure of an afferent neuron follows a layout conventional to most neurons, encompassing a cell body, dendrites, and an axon. Afferent neurons exhibit a pseudo-unipolar structure, meaning the nerve cell's axon and dendrite emanate from the same branch off the cell body before the axon eventually bifurcates, creating two axonal roots. One root extends to the sensory organ, while the other communicates with the spinal cord. This structure aids rapid signal transmission from the sensory organ to the spinal cord, enabling the immediate interpretation of sensory information. + +The operation of afferent neurons is essential for our interaction with and interpretation of our surroundings. When an external stimulus impacts one of our sensory receptors, these receptors generate an electrical impulse. The afferent neuron carries this impulse, via its axon, from the peripheral body to the central nervous system, triggering the appropriate response. Therefore, afferent neurons effectively serve as the biological relay team, connecting the world outside our bodies to the world inside, enabling us to sense and react to changes in our environment." DOI:10.1146/annurev.neuro.29.051605.113024|DOI:10.1523/JNEUROSCI.15-12-07757.1995|DOI:10.1038/nrn2993|DOI:10.1016/j.neuron.2013.07.051|DOI:10.1023/B:NEUR.0000010080.62031.f0 +387 CL:0000555 CL_0000555 "Neuronal brush cells are a unique type of sensorial cell found primarily within the mammalian respiratory and gastrointestinal tracts, especially in the throat and nose regions. Despite their alternative nomenclature, these cells are not neurons per se, but rather, they exhibit neuron-like properties and structure. The name 'brush cell' is derived from their distinctive morphology, characterized by blunt, brush-like microvilli protruding from the apical surface of the cell. + +The primary function of neuronal brush cells is detecting extracellular changes and stimuli, acting as intermediaries between sensory neuronal signals and their targets. They act as chemosensors, responding to changes in the chemical environment. It is thought that brush cells detect chemical contents in the mucosal lining of the nasal and oral cavities and convert this to a chemical signal which is then conveyed to the brain, contributing to the mechanics of smell and taste. This might also suggest a role in monitoring bacterial populations and regulating inflammatory reactions within the respiratory and gastrointestinal tracts. + +Due to their strategic positions within the respiratory and gastrointestinal systems, the neuronal brush cells also play a part in maintaining the balance of physiological processes. In the respiratory system, they may help mediate local immune responses and protect against potential pathogens. In the gastrointestinal tract, they're thought to aid in the control of food intake by sending signals to the brain once they detect certain nutrients. " DOI:10.1164/rccm.200502-203WS|DOI:10.1111/j.1469-7580.2007.00738.x|DOI:10.1254/jphs.11R08CP|DOI:10.1126/sciimmunol.aax7224|DOI:10.1007/s00441-009-0907-6 +388 CL:0000561 CL_0000561 "Amacrine cells are unique types of retinal neurons found in the eye's inner plexiform layer (IPL). They are particularly crucial in the visual system and form part of the complex network of cells that transmit and process signals from photoreceptors to the brain. Morphologically diverse with over 30 types identified, such diversity contributes to their wide range of functions, taking on an intermediary role in the transmission of visual information. For example, the AII amacrine cell, is crucial in enabling low-light vision or 'scotopic vision,' which allows resounding detailed vision in low-light environments, an essential evolutionary adaptation. + +One primary function of amacrine cells is to mediate inhibitory neurotransmission within the retina. This operation occurs via two primary neurotransmitters: glycine and gamma-aminobutyric acid (GABA). These neurotransmitters limit the activity of ganglion and bipolar cells, adding a layer of complexity to the image processing system by refining and modulating the output signals sent to the brain for interpretation. Beyond inhibitory action, these cells also play a role in adaptive processes, like adjusting to different light levels. + +Also, amacrine cells facilitate lateral interactions in the retina, both laterally among themselves as amacrine- amacrine cell interactions and laterally with bipolar and ganglion cells, contributing to signal summation and specific vision properties such as direction selectivity. In summary, amacrine cells play vital roles, emphasizing the importance of local processing within the visual system, enhancing our ability to interpret complex visual stimuli effectively." DOI:10.1017/S0952523811000368|DOI:10.1016/S0896-6273(00)80478-X|DOI:10.1523/JNEUROSCI.12-04-01394.1992|DOI:10.1017/S0952523812000028|DOI:10.1523/JNEUROSCI.4212-09.2010 +389 CL:0000573 CL_0000573 "Retinal cone cells, or simply cone cells, are one out of the two types of photoreceptor cells in the retina, the other being retinal rod cells. They function by converting light into signals that can lead to a visual perception. These cells are less sensitive to light compared to rod cells, but they play a crucial role in our vision system for their ability to perceive color and provide sharp visual acuity. They are responsible for our daylight and color vision, enabling an individual to perceive fine detail and rapid changes in light levels. + +Cone cells are specialized and named based on the absorption spectra of the visual pigments they contain, giving rise to three types of cone cells: short-wavelength S-cones (blue cones), middle-wavelength M-cones (green cones), and long-wavelength L-cones (red cones). The distribution of these cones across the retina differs, with greater densities at the central fovea region, contributing to why our central vision is so sharp and color-detailed compared to peripheral vision. + +The outer segments of retinal cone cells house the photopigments that absorb light and initiate the process of phototransduction, a biochemical event by which the light signal is transformed into an electrical signal. When a cone cell is stimulated by light, an electrochemical reaction triggers nerve impulses, which are then transmitted to the brain by the optic nerve. There, these impulses are processed into the images that we see. Each type of cone responds to different wavelengths of light, enabling us to perceive a spectrum of color. By working in conjunction with rod cells, which are adapted for low-light vision scenarios, the cone cells provide us with a comprehensive and adaptable vision system." DOI:10.1016/j.preteyeres.2009.05.003|DOI:10.1016/j.preteyeres.2010.11.001|DOI:10.1364/JOSAA.10.002491|DOI:10.1126/science.3576186|DOI:10.1113/JP282058 +390 CL:0000604 CL_0000604 "Retinal rod cells, often referred to simply as ""rod cells”, are a specialized type of photoreceptor cells found in the retina. Their primary function is to detect and convert light into electrochemical signals, which are then transmitted to the brain via nerve impulses. Compared to other types of photoreceptor cells, namely retinal cone cells, rod cells are more sensitive to light, and thus play a crucial role in night and peripheral vision. + +Rod cells are named for their long, cylindrical shape, which is distinct from the cone-like shape of retinal cone cells. The structure of a rod cell is complex, with different sections responsible for various aspects of its function. The outer segment contains densely packed, light-sensitive membrane discs filled with a pigment called rhodopsin. When light hits rhodopsin, it prompts a chemical reaction that leads to the generation of electrochemical signals. These signals are processed in the cell's inner segment, which contains the cell's primary organelles, including the nucleus and mitochondria, and transmitted through the cell's synaptic terminal to the secondary neurons in the retina. + +Rod cells are distributed across the majority of the retina, with the highest density found in the peripheral edges. This distribution, coupled with their high sensitivity to light, explains why rod cells contribute significantly to peripheral and low-light vision. However, they do not pick up color and have low spatial acuity, which means that while rod cells can detect the presence of light and movement, the finer details and colors of an image are processed mainly by cone cells. Together, rod cells and cone cells work in concert to enable a wide range of visual capabilities, making vision a complex and intricate biological process." DOI:10.1016/j.preteyeres.2016.06.002|DOI:10.1016/0968-0004(83)90235-9|DOI:10.1113/JP282058|DOI:10.1002/cne.902920402|DOI:10.1038/eye.2015.236 +391 CL:0000598 CL_0000598 "Pyramidal neurons, or pyramidal cells, are a distinctive type of neuron named for the triangular shape of their soma, or cell body. The primary characteristic of these neurons is a large apical dendrite that ascends toward the cortical surface, numerous basal dendrites, and a single axon. These neurons are found within parts of the brain including the cerebral cortex, the hippocampus, and the amygdala, playing a critical role in cortex communication, cognitive function, and the relay of information within the brain's neural network. + +Functional roles of pyramidal neurons depend largely on their localization. However, all types of these neurons serve as principal cells within the grey matter of the brain, transmitting signals over long distances. Primarily, pyramidal cells function as excitatory neurons; they disseminate action potential outputs to other neurons which they are connected to across the synapse. In the cerebral cortex, pyramidal neurons are paramount for sensory perception and motor command, while those located in the hippocampus involve in memory and learning processes. + +Firing properties of these neurons such as regular spiking and bursting are notable features thought to play a role in synaptic plasticity and signaling. Together, their unique anatomical structure and intricate connectivity underpin their critical function in brain neural networks, significantly contributing to human cognitive abilities. In addition, abnormalities in pyramidal neurons have been linked to a range of neurodegenerative and psychiatric disorders, emphasizing their importance in maintaining healthy neural function." DOI:10.1038/nrn2286|DOI:10.1093/cercor/bhg093|DOI:10.1002/jnr.23978|DOI:10.1038/s41583-019-0125-5|DOI:10.1016/S0896-6273(01)00447-0 +392 CL:0000617 CL_0000617 "GABAergic neurons are a vital type of neural cell that is primarily responsible for releasing the neurotransmitter gamma-aminobutyric acid (GABA), from which they derive their name. These neurons are abundant in the brain, forming the main inhibitory network. GABA is imperative for dictating the speed at which neural networks operate, preventing overactivity, and playing a crucial role in tasks involving precision and timing. The balance between the excitatory activity of neurons using the neurotransmitter glutamate and the inhibitory activity regulated by GABAergic neurons is fundamental to the healthy function of the brain and nervous system. + +These neurons have a complex and specific system that synthesizes and packages GABA, ensuring its proper release during neurotransmission. Enzymes convert glutamate, the main excitatory neurotransmitter, to GABA within the neuron. This GABA is then packed into vesicles that await release into the synaptic cleft, the space between communicating neurons. Once released, GABA binds to receptors on the post-synaptic neuron, typically resulting in increased polarization of this neuron’s membrane potential and thereby decreasing its ability to generate an action potential, which is fundamental to the process of neuronal signaling. This inhibitory process keeps the brain's excitatory systems in check, preventing overexcitation that could lead to pathologies like seizures or mood disorders. + +The diverse populations of GABAergic neurons with their specific firing patterns and styles of GABA release enable a wide variety of nuanced effects on network activity, contributing to the finely tuned regulation of behavior and cognition. Alterations in GABAergic neurotransmission can lead to various neurological and psychiatric disorders, including epilepsy, schizophrenia, and depression. " DOI:10.1038/s41583-020-0344-9|DOI:10.1016/j.neuint.2012.02.013|DOI:10.1007/s11064-014-1473-1|DOI:10.1517/14728222.9.1.153|DOI:10.1016/j.neuroscience.2021.06.037 +393 CL:0000644 CL_0000644 "Bergmann glial cells, also known as Bergmann glia or Bergmann astrocytes, are specialized astrocytes located in the cerebellum, specifically in the Purkinje cell layer. They were discovered and named after the German histologist Karl Bergmann and are known for their characteristic morphology. Unique to Bergmann glial cells is their long, fibrous processes, which extend through the molecular layer to the cerebellar surface, aligning parallel to the Purkinje cells' dendrites. These extensions play a detailed role in the structural organization and function of the cerebellum. + +The primary function of Bergmann glial cells is to support and nourish the adjacent neuronal cells, especially the Purkinje cells. Their strategic arrangements around synapses or nerve junctions also indicate their role in facilitating communication between neurons and in modulating synaptic plasticity. The glial cells remove excess neurotransmitters from the synaptic clefts and thus help maintain homeostasis. An additional important role of Bergmann glia is in the guided migration of granule cells during cerebellar development. This guidance is critical for the proper formation and arrangement of the cerebellar circuitry. + +In addition to these roles, recent studies have revealed a vital function of Bergmann glial cells in maintaining the overall health and functioning of the cerebellum. In instances of cerebellar injury or disease, these cells respond proactively and change their morphology and activity, a process known as reactive gliosis. This response seems to protect and restore the neural circuits. However, aberrant activation of Bergmann glial cells has been associated with several neurodegenerative diseases and disorders, such as spinocerebellar ataxia, underscoring their significance in the pathobiology of the nervous system." DOI:10.1016/S0074-7742(08)60530-9|DOI:10.1080/14734220600724569|DOI:10.1002/jnr.10197|DOI:10.1007/s12035-013-8405-y|DOI:10.1038/nn1750 +394 CL:0000636 CL_0000636 "Mueller cells, also referred to as Műller glial cells, are a type of radial glial cell found specifically within the retina, the light-sensitive tissue lining the back interior surface of the eye. They derive their name from Heinrich Müller, who first described these cells in the mid-nineteenth century. These support cells contribute to maintaining the homeostasis and structural integrity of the retina. Mueller cells span the entire thickness of the retina, thus representing the only cell type that traverses all layers. + +Mueller cells play a crucial role in maintaining the metabolic environment of retinal neurons and participating in the visual signal transduction. They have a unique organization and possess a wide range of processes, giving them direct contact with virtually every type of cell in the retina—including photoreceptors, bipolar cells, and ganglion cells. These cells actively uptake and recycle neurotransmitters, modulate chemical levels within the extracellular space, and are involved in potassium siphoning, thus supporting neuronal signaling. Due to these functions, they play a vital role in maintaining the physiological and functional stability of the retina. + +Moreover, Mueller cells are also responsible for maintaining the structural integrity of the retina. They serve as the retinal framework by providing structural support to neurons and blood vessels. They contribute to the formation and maintenance of the inner limiting membrane, comprising their end-feet at the vitreous surface. Additionally, they play an essential role during injury or disease, exhibiting reactive gliosis – a process where these cells undergo morphological and functional changes to aid in repair and protection from further damage. While their protective role is important, it's also worth noting that overactivation of Mueller cells may result in retinal scarring or degeneration, reinforcing their complex and delicate role in retinal health and disease." DOI:10.1016/j.preteyeres.2006.05.003|DOI:10.1002/glia.22477|DOI:10.3389/fendo.2013.00048|DOI:10.1007/s10792-020-01477-3|DOI:10.1038/78774 +395 CL:0000679 CL_0000679 "Glutamatergic neurons primarily utilize the amino acid neurotransmitter glutamate to transmit signals across synapses. Found ubiquitously throughout the brain, these neurons are critical to almost every function of the central nervous system. Glutamate plays a significant role as an excitatory neurotransmitter and is instrumental in cognitive functions like learning and memory. + +Functionally, glutamatergic neurons are responsible for receiving, processing and transmitting information in the brain, and play a vital role in the mechanism of synaptic plasticity. Synaptic plasticity refers to the ability of the connections between two neurons to change in strength in response to modifications in their activity level, a fundamental process of learning and memory formation. This ability to adapt, reshape, and form new synapses greatly affects the overall signaling, behavior, and health of neural networks. + +However, the importance of glutamatergic neurons extends beyond cognitive functions. Dysfunction in glutamatergic systems has been implicated in a plethora of neurological disorders including epilepsy, Alzheimer's and Parkinson's disease, schizophrenia, and mood disorders. The central role of these neurons in both the normal function and dysfunction of the brain underscores their critical role in neuroscience." DOI:10.1016/j.pbb.2011.08.008|DOI:10.1016/S0166-4328(02)00272-3|DOI:10.1155/2016/7607924|DOI:10.1016/j.neuropharm.2021.108719|DOI:10.1038/nrd2462 +396 CL:0000695 CL_0000695 "Cajal-Retzius cells are unique, early-born neurons found within the developing cerebral cortex and hippocampus. They are named after Santiago Ramon y Cajal and Gustaf Retzius, who first discovered them independently in the late 19th century. These neurons are characterized by horizontally oriented bipolar or multipolar cell bodies, facilitating their function in structuring the architecture of the cortex. + +The primary role of Cajal-Retzius cells is to mediate the correct formation of the cortical layers in the developing brain. They accomplish this chiefly through the secretion of the extracellular matrix protein Reelin, which interacts with receptors on migrating neurons to control neuronal migration and position. The Reelin signal provided by Cajal-Retzius cells is essential to establish the cortical plate, where new neurons arising from the ventricular zone accumulate and form the recognizable layered structure of the cortical region. Disruptions in Reelin signaling can lead to reeler-like phenotypes characterized by inversion of cortical layers, demonstrating the importance of these cells during normal brain development. + +In addition to layer formation, Cajal-Retzius cells also play a role in synaptic plasticity, which is a key aspect of learning, memory, and cognitive function. It has been suggested that these cells are involved in establishing the first functional synapses in the developing cortex, providing initial neural network activity. Furthermore, they have been linked to the modulation of gamma-aminobutyric acid (GABA) trafficking, excitatory-inhibitory balance, and thus, the fine-tune of the neural network activity during early postnatal life. Despite their disappearance shortly after birth in rodents and during early adolescence in humans, Cajal-Retzius cells lay the groundwork for the structure and functionality of the brain's cortical region." DOI:10.1016/S0166-2236(97)01164-8|DOI:10.1155/2014/597395|DOI:10.1038/nrn2009|DOI:10.1111/j.1440-169X.2009.01102.x|DOI:10.1523/JNEUROSCI.1407-14.2014 +397 CL:0000708 CL_0000708 "Leptomeningeal cells, often referred to as pia-arachnoid cells or pia mater cells, are a specific type of cells found in the leptomeninges--the inner two layers (the arachnoid mater and pia mater) of the meninges which are the membranes covering the brain and spinal cord. They form a critical structural and functional barrier, playing important roles not only in the protection of the central nervous system (CNS), but also in the regulation of its homeostasis. + +Functionally, leptomeningeal cells display a wide range of activities that contribute to the maintenance and defense of the CNS. These cells are responsible for the production of cerebrospinal fluid (CSF), a clear bodily fluid that fills the subarachnoid space in the brain and spinal cord. The CSF produced by leptomeningeal cells is vital for providing nutrients and removing waste products from the nervous tissue. It also is important for acting as a cushion or buffer for the brain, providing basic mechanical and immunological protection to it. + +In addition to CSF production, leptomeningeal cells also have a role in maintaining the immune privilege of the CNS. They act as physical and immunological barriers, restricting the movement of cells and large molecules from blood into CSF and effectively limiting the exposure of the CNS to the immune system. This protects the delicate brain tissue from damaging immune responses. Furthermore, leptomeningeal cells can also respond to injury or disease by undergoing changes that help contain CNS damage and orchestrate the healing response. This includes proliferation and transformation into a reactive state to facilitate repair, demonstrating their significant role in CNS pathophysiology." DOI:10.1111/j.1365-2990.1991.tb00739.x|DOI:10.1038/nature16939|DOI:10.1046/j.1471-4159.1996.67030964.x|DOI:10.1146/annurev-immunol-102319-103410|DOI:10.1038/s41467-023-42825-y +398 CL:0000751 CL_0000751 "Rod bipolar cells constitute a significant component of the retinal neural network and play a pivotal role in signal transmission from rod photoreceptor cells to the other subsequent neuronal cells within the vision system. They belong to the category of interneurons, or connector cells, effectively conveying visual information under low light conditions. Non-mammalian and mammalian visual systems feature these cells serving as the primary conduit for scotopic (night vision) signals. + +These cells harness their strategic position in the retina's inner nuclear layer to receive information from the rod photoreceptor cells and transmit it to amacrine and ganglion cells. Structurally, they are named bipolar due to their distinctive shape, with dendrites extending towards the outer retina to connect with rod cells, while their axons lead inwards to form synapses with ganglion and amacrine cells in the inner plexiform layer. Each rod bipolar cell tends to interface with several rod cells and several downstream neurons, forming intricate networks. + +Bearing intricate dendritic trees, these cells can integrate responses from multiple rod cells efficiently, amplifying the retinal signal's strength. They employ glutamate, a type of neurotransmitter, to govern synaptic communication between photoreceptor cells and downstream neurons. This stratified arrangement of rod bipolar cells endows them with the capability to translate light signals into neural signals, predominantly maintaining the spatial and temporal resolution of our visual perception in dim lighting. They are key to our night vision and our ability to detect changes in our light environment. +" DOI:10.1038/nrn3783|DOI:10.1016/j.visres.2004.07.043|DOI:10.1002/cne.23370|DOI:10.1038/294592a0|DOI:10.1007/s004410000304 +399 CL:0001031 CL_0001031 "The cerebellar granule cell is a predominant type of neuron located in the granular layer of the cerebellum. These cells are among the smallest neurons in the brain, yet they constitute the bulk of the neural cells in the cerebellum, making cerebellar granule cells the most populous type of neuron in mammals. The granule cells of the cerebellum play an essential role in the functioning of the cerebellar cortex by participating in a complex neuronal network that results in coordination and fine-tuning of motor activities. + +Initiating and controlling movement is the primary functional role of cerebellar granule cells. They achieve this through highly sophisticated neuronal networking. Each granule cell gives rise to an axon that ascends into the molecular layer of the cerebellar cortex, where it bifurcates into T-shape to form parallel fibers that run perpendicular to the Purkinje cell dendrites. This structure allows a single granule cell to make synaptic contact with hundreds of Purkinje cells and thereby influence their output. Cerebellar granule cells contribute to the generation of movement by transforming unstructured input from mossy fibers into organized output to the Purkinje cells. + +Understanding the role of cerebellar granule cells in neural plasticity is an emerging area of study. Recent research suggests that cerebellar granule cells may be involved in learning and memory processes, particularly those related to motor learning. They display unique synaptic plasticity, equipping them with the ability to adjust their response over time, which aids in the learning and storage of motor patterns. " DOI:10.3389/fncir.2020.611841|DOI:10.1038/nn.4531|DOI:10.1152/jn.1998.80.5.2521|DOI:10.1016/B978-0-444-63356-9.00002-9|DOI:10.1038/nrn3312 +400 CL:0000740 CL_0000740 "Retinal ganglion cells (RGCs) are a type of neuron located near the inner surface of the retina, playing a critical role in the visual pathway. There are approximately 1 million RGCs in a typical human eye, each receiving inputs from multiple photoreceptor cells. As the only neurons in the retina that send information to the brain, they are the final output neurons of the vertebrate retina, and their axons constitute the majority of fibers in the optic nerve. + +The primary function of RGCs is to receive visual information from photoreceptors via intermediary bipolar and amacrine cells, process it, and transmit it to the brain through their axons. The information that RGCs relay encompasses various aspects of the visual field, including color, contrast, brightness, and motion. A diverse population of RGCs, up to 30 distinct subtypes, each contributes to a specific aspect of vision, such as object motion, edge detection, or color contrast, illustrating the complexity of visual data processing that occurs already at the retinal level. + +RGCs also play a role in the regulation of circadian rhythms and the pupillary light reflex. Some RGCs contain the photopigment melanopsin and respond directly to light, separately from the retinal rod and cone cells found in the outer retina. These photosensitive RGCs are primarily involved in subconscious vision, particularly the regulation of circadian rhythms and the pupillary light reflex in response to changes in ambient light intensity. Hence, RGCs serve a highly specialized and diverse role in transmitting visual information and regulating light-dependent responses, view modalities, and key physiological processes." DOI:10.1146/annurev-neuro-071714-034120|DOI:10.1002/cne.10652|DOI:10.1038/nature16468|DOI:10.1111/j.1444-0938.2010.00479.x|DOI:10.1016/j.neuron.2019.07.016 +401 CL:0000745 CL_0000745 "Retina horizontal cells are a specialized type of neuron found in the inner nuclear layer of the retina. They play a crucial role in the visual system by integrating and regulating the input from multiple photoreceptor cells, which sense and respond to light. Retina horizontal cells are so named due to their characteristic flat horizontal orientation, with their dendrites and axons coursing laterally in a plane parallel to the retinal surface. + +Retina horizontal cells are synaptically connected with photoreceptor cells (i.e., cones and rods) and bipolar cells. Their primary function is to facilitate the process of lateral inhibition, where an excited neuron reduces the activity of its neighbors. This capability is central to the phenomenon of ""contrast enhancement"" in visual perception, where the borders between light and dark areas are accentuated to better resolve images. Retina horizontal cells receive inputs from these neighboring photoreceptor cells and transmit their inhibitory output to not only photoreceptor cells but also bipolar cells, fine-tuning the responsiveness to changes in light intensity and differences in wavelengths. + +Moreover, retina horizontal cells play a substantial role in adaptation of retinal response to different light levels. In bright light conditions, they aid the reduction of the overall response to light stimuli, thus aiding in the prevention of photoreceptor saturation. These neurons are adept at adjusting the gain and thus the dynamic range of photoreceptors supporting the vision process under variable lighting conditions - from dim moonlight to bright sunshine. Therefore, retina horizontal cells contribute considerably to the adaptability, sharpness, and detail perception of our visual system." DOI:10.3389/fnana.2016.00077/full|DOI:10.1113/JP274177|DOI:10.1073/pnas.88.8.3310|DOI:10.1371/journal.pbio.1001107|DOI:10.1167/5.4.5 +402 CL:0000748 CL_0000748 "The retinal bipolar neuron is an integral part of the eye, specifically located within the retina. They are secondary neurons in the visual pathway and primarily serve to transmit information from photoreceptor cells, which respond to light, to retinal ganglion cells, which carry the signal to the brain. As such, these cells play a pivotal role in our ability to interpret and perceive visual information. + +The structure of retinal bipolar neurons is unique and significant to their function. They are termed ""bipolar"" due to their morphology, having two poles: a single dendrite on one end and an axon on the other. The dendrite end connects to photoreceptor cells (rods or cones), while the axon end synapses with retinal ganglion cells. In the center of the dendrite and axon lies the cell body, which houses the cell's nucleus and other vital organelles. + +At the functional level, retinal bipolar neurons can be categorized into ON and OFF types based on their response to light. 'ON' bipolar cells are depolarized (electrical potential across the cell membrane decreases) under light conditions, thereby increasing their rate of neurotransmitter release onto the downstream ganglion cells. In contrast, 'OFF' bipolar cells are hyperpolarized (electrical potential increases) in light conditions, decreasing their rate of neurotransmitter release. This dual system allows for a fine-tuned response and the ability to perceive differences in light intensity and contrast, thus creating a nuanced and detailed visual world." DOI:10.1038/nrn3783|DOI:10.1016/j.ydbio.2021.09.005|DOI:10.1126/science.201028|DOI:10.1017/S0952523810000209|DOI:10.1016/j.preteyeres.2008.03.003 +403 CL:0002319 CL_0002319 "Neural cells are highly specialized and diverse types of cells that make up the nervous system, which includes the brain, spinal cord, and peripheral nerves. They are integral to the body's communication system, transmitting information to and from the brain and spinal cord to different parts of the body. They play a vital role in various fundamental bodily processes including the perception of sensory stimuli, motor control, regulation of physiological functions, and cognition. + +Neurons are a major type of neural cell composed of a cell body (also known as the soma), which houses the nucleus and most of the cell's organelles, and an intricate network of extensions known as axons and dendrites. These structures allow for communication with neighbouring neurons. Axons are responsible for carrying electrical signals away from the cell body, while dendrites receive information from other neurons and transmit them to the cell body. At the end of each axon are neurotransmitter-filled vesicles, which upon receiving the axon's electrical signals, release their contents into the synapse, the gap between neurons. This neurotransmitter release is how neurons transmit signals to each other. + +Each neuron can be connected to thousands of other neurons, forming interconnected networks that make up the complexity of the nervous system. Their ability to receive and transmit information, process it, and initiate a response on a split-second timescale makes neurons cells essential to the functioning of all multicellular animals. Importantly, neurons are generally non-replicative in nature, meaning they do not undergo cell division. This characteristic underscores their uniquely specialized and enduring identity as individual entities within the nervous system. However, they retain a dynamic ability to adapt and modify their connections and functions, which is at the root of learning and memory." DOI:10.1038/nn.4366|DOI:10.1016/j.neuron.2017.10.007|DOI:10.1038/s41586-021-03941-1|DOI:10.1002/cyto.a.20666|DOI:10.1038/nrn3962 +404 CL:0002453 CL_0002453 "An oligodendrocyte precursor cell (OPC), also commonly referred to as an oligodendrocyte progenitor cell, is an undifferentiated or immature type of cell found in the nervous system that differentiates into a fully mature oligodendrocyte. Oligodendrocytes are known for their role in creating the protective myelin sheath that covers and insulates neurons in the central nervous system, enhancing the speed and efficiency of neurological signal transmission. OPCs contribute to this vital process by providing a consistent source of new oligodendrocytes. + +OPCs are unique for their remarkable flexibility and adaptability, making them a critical element in many neurological processes. They are involved in neurogenesis and reparative functions as they can proliferate and be mobilized to areas of brain injury to aid in tissue repair and regeneration. Particularly, they play a significant role in the recovery and remyelination of damaged neurons, attributing to their prolific distribution in both gray and white matter areas of the brain and spinal cord. + +Recent research has revealed the broader plasticity of OPCs. Studies have shown that OPCs can also differentiate into astrocytes and neurons under certain conditions, enlarging their role from just players in myelination to contributors in maintaining the integrity and adaptability of the central nervous system. Furthermore, these cells have been found to interact directly with neurons and take part in synaptic transmission, implying a more complex role in neural network activity. " DOI:10.1016/j.ceb.2021.05.003|DOI:10.1111/j.1460-9568.2006.04625.x|DOI:10.1016/S0166-2236(00)01691-X|DOI:10.1016/j.neuron.2011.05.013|DOI:10.1101/gad.344218.120 +405 CL:0002608 CL_0002608 "Hippocampal neurons, also known as hippocampal pyramidal cells, specifically reside within the hippocampus, a region of the brain that plays key roles in learning, memory, and spatial processing. The structure of the hippocampal neuron contains a pyramidal cell body from which apical and basal dendrites extend. These dendrites receive synaptic inputs, and the integrated signals are then propagated down the axon to instigate synaptic transmission with downstream neurons. These complex physiological structures allow for intricate connectivity and communication with other neurons. + +Hippocampal neurons have a sophisticated functionality that profoundly influences various cerebral tasks. One foremost role is in learning and memory, particularly episodic memory and spatial memory. Remarkably, these neurons are capable of undergoing long-term potentiation (LTP) and long-term depression (LTD), which are physiological processes thought to be the cellular basis of learning and memory. Additionally, hippocampal neurons play a critical role in the formation of cognitive maps, which are mental representations of spatial relationships that help in navigation and understanding spatial environments. + +The health and activity of hippocampal neurons are of considerable importance. Aberrant functioning of hippocampal neurons has been implicated in several neurological disorders, such as Alzheimer’s disease, epilepsy, and depression. For example, in Alzheimer's disease, these neurons are among the first to be damaged, leading to early memory loss and disorientation. Conversely, the activation of newborn neurons in the hippocampus has been associated with resilience to stress and antidepressant effects. " DOI:10.1038/s41583-019-0125-5|DOI:10.1002/(SICI)1098-1063(1999)9:4<365::AID-HIPO4>3.0.CO;2-T|DOI:10.1016/j.semcdb.2011.07.017|DOI:10.1016/j.neurobiolaging.2003.12.005|DOI:10.1016/j.biopsych.2006.03.082 +406 CL:0002603 CL_0002603 "Astrocytes of the cerebellum, also known as cerebellar astrocytes, constitute a major subtype of glial cells in the cerebellum, an integral region of the brain responsible for regulating motor movements and cognitive processes. These astrocytes are unique to the cerebellum, differing in morphological and functional characteristics from astrocytess located in other parts of the nervous system. They play a crucial role in managing the brain's complex microenvironment by maintaining neuronal health, supporting biochemical pathways, and contributing to targeted neural communication. + +Astrocytes of the cerebellum operate through an interactive network with neurons, blood vessels, and other glial cells. They provide physical and nutritional support for neurons, helping preserve neuronal survival and function. These cells effectively manage the extracellular ion and neurotransmitter balance, pivotal for synaptic transmission. They also contribute to the maintenance of the blood-brain barrier, a semi-permeable membrane that safeguards the brain from harmful substances in the bloodstream, ensuring cerebral homeostasis. + +Furthermore, cerebellar astrocytes are involved in the processing and modulation of synapses, the junctions where neurons exchange information. They regulate the release and uptake of neurotransmitters, which helps in synaptic plasticity, a process that is integral in learning and memory. Moreover, these astrocytes produce and secrete various neurotrophic factors, including brain-derived neurotrophic factor (BDNF), which is crucial for neurogenesis and synaptic plasticity. Therefore, astrocytes of the cerebellum not only execute supportive roles but are also actively involved in modifying neuronal function and enabling neuroplasticity." DOI:10.1016/j.pneurobio.2013.08.001|DOI:10.1007/s12311-019-01046-0|DOI:10.1038/nrn1824|DOI:10.1155/2014/232105|DOI:10.1016/j.brainres.2006.06.008 +407 CL:0002627 CL_0002627 "Mature astrocytes are specialized glial cells found primarily in the central nervous system (CNS), which consists of the brain and the spinal cord. They are named aftertheir star-like shape. Mature astrocytes are derived from radial glia, with the transition from radial glia to immature astrocytes, followed by maturation into the final functionally specialized form. They are further classified into two basic types: protoplasmic astrocytes present mainly in the grey matter and fibrous astrocytes in the white matter. + +Functionally, mature astrocytes play a central role in both the structure and function of the CNS through regulation of neurons. By secreting molecules, such as cytokines, that influence the formation, functioning, and elimination of synapses, they actively participate in the formation and modulation of synaptic connections between neurons. Additionally, they also possess a unique capability known as gliotransmission, referring to the astrocytes' ability to respond to and release neurotransmitters, which impacts neuronal signaling. + +The mature astrocytes also maintain the brain's homeostasis, which includes controlling the chemical environment, providing nutrients to nervous tissues, regulating blood flow, responding to injury, and maintaining the blood-brain barrier, a crucial defense mechanism of the brain. They metabolize neurotransmitters like glutamate to prevent neurotoxicity and help in the detoxification process. Furthermore, these cells play a vital role in neuroinflammation and reactive gliosis, a response to trauma or neurodegenerative diseases, and assist in repairing damaged neural tissues. Thus, the versatile mature astrocytes play multiple roles and significantly contribute to the correct functioning and reparative process of the CNS." DOI:10.1177/1073858409342593|DOI:10.1002/glia.22836|DOI:10.1016/j.neuron.2017.09.056|DOI:10.1002/jnr.24922|DOI:10.1002/glia.23908 +408 CL:0005025 CL_0005025 "Visceromotor neurons, also known as autonomic motor neurons, are an integral component of the body's autonomic nervous system, which controls and regulates internal body processes such as digestion, circulation, and respiration, autonomously from conscious control. These neurons regulate the motor functions of internal organs and glands, and serve as the effector neurons of the autonomic nervous system, conveying the signals from the central nervous system to execute actions.Visceromotor neurons are predominantly subdivided into two main functionally distinct categories: sympathetic and parasympathetic neurons. + +Sympathetic visceromotor neurons tend to stimulate action, conserving energy for times of impending threat or when increased alertness is required. These neurons often act to increase heart rate, expand air passages allowing for greater oxygen flow to the muscles and brain, slow digestion, and produce a surge of glucose (sugar) in the bloodstream to cater to the energy demands during periods of heightened activity or stress. + +Parasympathetic visceromotor neurons typically take effect during periods of calm, and are responsible for what's often termed as ""rest and digest"" activities. They govern a variety of activities collectively aimed at restoring and conserving bodily energy. Parasympathetic visceromotor neurons act to conserve energy by slowing the heart rate, increasing intestinal and gland activity, and relaxing sphincter muscles in the gastrointestinal tract. The complementary functions of these two types of visceromotor neurons enable the body to maintain an overall balance, or homeostasis, responding appropriately under different conditions and demands. Without the dynamic and essential functioning of visceromotor neurons, the body would lose its capability to autonomously regulate essential processes, thereby exposing it to potentially harmful internal conditions. +" https://www.ncbi.nlm.nih.gov/books/NBK554616/|DOI:10.3389/fncel.2014.00293|DOI:10.1016/0165-1838(81)90068-0|DOI:10.1177/0148607108321705|DOI:10.3389/fphys.2021.700129 +409 CL:0007011 CL_0007011 "Enteric neurons, also known as the neurons of the enteric nervous system (ENS), form a vast and complex network within the walls of the gastrointestinal tract. These unique cells constitute the principal component of the ENS, which is often referred to as the ""second brain"" or the gut's brain, due to its autonomy from the central nervous system (CNS). While the ENS does communicate with the CNS, it can function independently, thereby playing an essential role in maintaining the body's homeostasis. + +Enteric neurons are incredibly diverse in function and morphology. Integral to essential processes like peristalsis, secretion, and blood flow regulation, these neurons are further classified into different types based on their roles. The organization of the ENS is characterized by two main ganglionated layers: the inner submucosal (Meissner's) plexus, involved primarily in regulating gastrointestinal blood flow and epithelial cell function, and the outer myenteric (Auerbach's) plexus, which predominantly manages gut motility. + +Enteric neurons play a significant role in sensing and responding to changes within the gut environment. First, they detect physical and chemical changes, for instance, the arrival of food, and respond accordingly by adjusting gut motility and secretions. Second, they communicate information about the state of the gut to the CNS; however, much of the routine detailed management of the digestive system is carried out within the ENS itself. In addition, they also interact with the gut's large microbial population and the immune system, playing a pivotal role in health and disease. Dysfunctions or alterations in the enteric neurons may contribute to various gastrointestinal disorders, such as functional dyspepsia or irritable bowel syndrome, and neurodegenerative diseases such as Parkinson's. +" DOI:10.1038/nrgastro.2012.32|https://www.ncbi.nlm.nih.gov/books/NBK551559/|DOI:10.1038/s41575-020-0271-2|DOI:10.1016/j.immuni.2017.05.011|DOI:10.1038/nrgastro.2016.107 +410 CL:0008031 CL_0008031 "Cortical interneurons are a specialized type of neuron predominantly found in the cerebral cortex, the brain's outer layer responsible for higher cognitive functions. They constitute approximately 20-30% of all cortical neurons and are characterized by their crucial role in inhibiting the activity of other neurons in the brain, adding a critical dimension of control to neural activity and information processing. + +These cortical interneurons are significantly implicated in maintaining the balance of excitation and inhibition in the cerebral cortex, which is essential for normal brain function. This balance allows the brain to respond appropriately to stimuli, modifying behavior and facilitating motor, sensory, and cognitive processes. Furthermore, cortical interneurons are instrumental in the generation of brain oscillations, rhythmic patterns of neuronal activity believed to contribute to various aspects of cognitive processes, such as attention, memory, and consciousness. + +Their unique function and morphology, along with the numerous subtypes distinguished by differences in physiological properties, molecular expression profiles, and connectivity patterns, highlight the complexity and diversity of cortical interneurons. Dysfunction or abnormal development of these cells has been linked to various neurological disorders, including epilepsy, schizophrenia, and autism. " DOI:10.1242/dev.132852|DOI:10.1016/j.conb.2017.08.018|DOI:10.1038/ncomms6333|DOI:10.1016/j.conb.2023.102703|DOI:10.1038/nrn3155 +411 CL:0009004 CL_0009004 "Retinal cells are specialized cell types located in the retina, a thin layer of tissue lining the rear of the eye that plays an integral role in vision. They include multiple categories including amacrine cells, retinal bipolar neurons and others. These cells work in conjunction to perceive and transmit visual information from the environment to the brain. + +For example, bipolar cells receive signals from photoreceptors and process them through electric signals, which are further passed on to the ganglion cells. Amacrine cells play a supporting role in this process. Retinal horizontal cells help to integrate and regulate the input from multiple photoreceptor cells, enabling the perception of contrast and edge, while amacrine cells aid in the early stages of visual processing by inhibiting bipolar and ganglion cells to increase contrast and perception of motion. The retinal ganglion cells, finally, transmit the visual information from the retina to the rest of the brain via their long axons that form the optic nerve. Together, these cells contribute to the vital function of converting light into signals, putting in motion the complex process of vision. +" https://www.ncbi.nlm.nih.gov/books/NBK545310|DOI:10.1017/S0952523811000344|DOI:10.1038/nrn3783|DOI:10.1016/j.neuron.2012.10.002 +412 CL:0010009 CL_0010009 "The camera-type eye photoreceptor cell is a highly specialized type of nerve cell found in the retina of the vertebrate eye. These cells contribute to the complex process of vision by transducing light into electrical signals that can be interpreted by the brain. This category includes two distinct subtypes of photoreceptor cells, retinal rod cells and retinal cone cells, which serve different roles in vision. + +Retinal rod photoreceptor cells are responsible for peripheral and night vision. They are highly sensitive to light and allow for low-light visibility, however, they are incapable of discerning color. Retinal cone photoreceptor cells, on the other hand, are essential for color perception and provide the high spatial acuity involved in central and daylight vision. These cone photoreceptors are further divided into three categories based on the type of light sensitivity: short-wavelength (S; blue), middle-wavelength (M; green), and long-wavelength (L; red). The human eye typically contains approximately 120 million rods and 6 million cones. + +The camera-type photoreceptor cells contain a photosensitive pigment called an opsin (rhodopsin in rods, and iodopsin in cones), which undergoes a structural change when it absorbs light, triggering a chemical cascade that alters the cell's membrane potential and leads to a change in its rate of neurotransmitter release. This signal is then transmitted to other retinal neurons, before being sent onwards to the brain. Complex interactions between the different types of photoreceptor cells and the brain eventually result in the perception of visual images. Rod and cone cells degrade and regenerate their photopigments at a constant rate, allowing the eye to continuously adapt to changes in light levels." DOI:10.1387/ijdb.041900wg|DOI:10.1016/j.preteyeres.2016.06.002|DOI:10.1038/eye.2015.236|DOI:10.1364/JOSAA.10.002491 +413 CL:0010011 CL_0010011 "The cerebral cortex GABAergic interneuron is a type of neuron found primarily in the brain's cerebral cortex. These neurons are distinguished by their primary inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) which plays a crucial role in managing the excitability of neurons. Interneurons, in general, function as primary regulators of data flow in the nervous system. They manage the communication between sensory and motor neurons, influencing our responses to environmental stimuli. + +The cerebral cortex GABAergic interneurons are particularly essential for the proper functioning of cerebral cortical networks. These neurons generate diverse inhibition patterns, creating a balance between excitation and inhibition in neuronal networks. This balance is fundamental in ensuring normal cortical processes such as sensory perception, memory, and cognitive functions. The diverse range of GABAergic interneurons contributes to generating distinct cortical rhythms which are linked with specific behavioral states, mental health, and neurological diseases. + +Alterations or disruptions in the function of cerebral cortex GABAergic interneurons can have serious implications, and have been associated with various neurological and psychiatric conditions such as epilepsy, schizophrenia, and autism. The heterogeneity of cerebral cortex GABAergic interneurons, in terms of their morphology, connectivity, and physiology, contribute greatly to the functional diversity of the cerebral cortex." DOI:10.1038/nrn2402|DOI:10.1016/j.neuron.2013.01.011|DOI:10.1038/nrn3155|DOI:10.1016/j.neuron.2018.10.009|DOI:10.1016/j.conb.2023.102703 +414 CL:0010022 CL_0010022 "Cardiac neurons are a specialized type of neuron found within the heart tissue. They are the primary constituents of the intrinsic cardiac nervous system, also known as the cardiac plexus or intrinsic cardiac ganglia, which is responsible for the regulation of the heart's rhythmic contractions and overall functioning. This group of neurons is integral to the autonomic control of the heart and plays a crucial role in modulating cardiac activity, thereby playing an essential role in maintaining cardiovascular homeostasis. + +These neurons are responsible for both the sympathetic and parasympathetic regulation of the heart’s function. In terms of sympathetic control, cardiac neurons respond to the release of norepinephrine, which increases heart rate, strength of contractions, and blood pressure. Conversely, with regards to parasympathetic control, these neurons respond to the neurotransmitter acetylcholine, which decreases heart rate, blood pressure, and the strength of contractions. Thus, the balance between these sympathetic and parasympathetic inputs regulated by cardiac neurons is essential for normal heart function. + +Cardiac neurons also partake in the transmission of pain signals during conditions such as myocardial ischemia, contributing to the symptomatology of ischemic heart disease. Additionally, abnormal function or pathological alterations in these neurons could lead to various cardiac dysfunctions, including arrhythmias and heart failure." DOI:10.1016/j.autneu.2016.08.006|DOI:10.1002/cphy.c150046|DOI:10.3390/jcdd7040054|DOI:10.1161/01.RES.84.8.921|DOI:10.1152/ajpregu.00183.2004 +415 CL:0010012 CL_0010012 "A cerebral cortex neuron, also known as a cortical neuron, is a unique type of cell found in the cerebral cortex, which is the outer covering of the brain. This region is critical to cognitive functions, sensory input processes, memory formation, attention, and consciousness. These neurons are one of the most abundant cell type in the cortex and allow for the intricate capabilities of the human brain due to their diverse characteristics and complex connectivity. + +The primary function of cortical neurons is to manage and interpret the sensory input being received by the brain, generating suitable motor output responses. They play a critical role in processing information and communication within the brain. These neurons are involved in the exchange of direct synaptic communication with thousands of other neurons. Due to the wide extent of their dendritic and axonal arbors, these neurons present a broad receptive field for incoming information and an expansive projecting field to convey integrated information. + +Cortical neurons further define the functional structure of the cerebral cortex by their type and connection. They can be broken down into two categories: excitatory projection neurons and inhibitory interneurons. The excitatory projection neurons are the principal neurons of the cerebral cortex and utilize glutamate as a neurotransmitter. They form the connections between the cerebral cortex and other brain regions, hence their tag as ""projection"" neurons. Conversely, inhibitory interneurons are local to the cerebral cortex and use gamma-aminobutyric acid (GABA) as a neurotransmitter, serving to regulate the activity of the projection neurons. Through these intricate interconnections, cerebral cortex neurons play a significant role in the higher cognitive functions of the human brain." DOI:10.1038/nrn2151|DOI:10.1016/j.tics.2022.08.012|DOI:10.1186/s13064-018-0104-y|DOI:10.1016/j.neuron.2011.01.015|DOI:10.1038/s41586-021-04230-7 +416 CL:0011005 CL_0011005 "GABAergic interneurons, a major subtype of neurons, are characterized by the secretion of gamma-aminobutyric acid (GABA) – the primary inhibitory neurotransmitter in the central nervous system (CNS) of mammals. These cells play a crucial role in balancing the excitatory and inhibitory neurotransmission within neural networks. GABAergic neurons are particularly important for maintaining homeostasis within the brain, and any imbalance in GABAergic neurotransmission is often associated with neurological disorders such as epilepsy, schizophrenia, and mood disorders, highlighting their significance in the nervous system. + +The primary function of GABAergic interneurons is to inhibit neural transmission or modulate the degree of activation of other neurons. They achieve this task by releasing GABA neurotransmitter, which binds to GABA receptors on other cells, resulting in a decrease of neuronal excitability. They form extensive circuits and are intricately involved in various neural processes including learning and memory, sensory perception, and motor control among others. Additionally, subsets of GABAergic interneurons serve as pacemakers in various brain rhythms thus contributing to cognitive processes such as attention and sensory perception. + +GABAergic interneurons are not a homogenous group, they vary in terms of morphology, distribution, and function in the brain. For example, interneurons in the hippocampus regulate the transmission of information by inhibiting the flow of excitatory signals as part of a feedback loop. Other types, found predominantly in the cerebral cortex (like basket cells), exert control over a larger network of cells. Thus, despite being inhibitory in nature, their impact on neuronal circuitry broadens the diversity of information flow within the brain, hence potentiating information processing and ensuring proper nervous system function." DOI:10.1016/j.neuron.2013.01.011|DOI:10.1016/S0893-133X(01)00225-1|DOI:10.1016/S0074-7696(02)13011-7|DOI:10.1038/s41583-019-0195-4|DOI:10.1152/physrev.00007.2017 +417 CL:1001474 CL_1001474 "Medium spiny neurons, constituting the main type of neurons found in the striatum of the brain, are key players in various pathways that facilitate a multitude of cognitive functions. Projecting dendrites laden with spines, these cells are equipped to receive a wide range of synaptic input, mainly from the cerebral cortex and the thalamus. The ""medium"" and ""spiny"" descriptive parts of the name stem from the neurons' size, which is intermediate when compared to other neurons, and the presence of numerous spines on the dendrites, which serve as critical points for synaptic connections. + +The primary function of medium spiny neurons lies within motor control and reward pathways, which are fundamental aspects of the basal ganglia circuitry. They act by receiving and integrating various excitatory and inhibitory inputs to generate a resultant inhibitory output, generally towards other basal ganglia structures. This inhibitory output is crucial to the balance within the basal ganglia system, which regulates voluntary movements, habitual behaviors, and cognitive and emotional functionalities. The medium spiny neurons act through the use of the neurotransmitter gamma-aminobutyric acid (GABA) and express high levels of dopamine D1 or D2 receptors, which facilitate communication within the brain's dopamine system. + +Disruptions or malfunctions in medium spiny neurons have been associated with several neurological and psychiatric disorders. For instance, in Huntington's disease, these neurons display a specific vulnerability, leading to motor control issues, cognitive decline, and psychiatric symptoms. Similarly, these neurons play critical roles in substance addiction, as the neurons' reward pathways can become sensitized or desensitized due to drug abuse." DOI:10.1523/JNEUROSCI.3833-10.2011|DOI:10.3389/fnbeh.2011.00047|DOI:10.1007/978-3-7091-0932-8_18|DOI:10.1016/j.tins.2007.03.008|DOI:10.1007/s13311-012-0112-2 +418 CL:1001509 CL_1001509 "Glycinergic neurons are a specialized type of neuron that primarily utilizes the inhibitory neurotransmitter glycine to transmit signals within the nervous system. Originating from the term 'glycine' and 'ergic' (pertaining to activity), glycinergic neurons contain and release glycine which acts on specific receptors, known as glycine receptors, found on the surface of neuron cells. Glycinergic neurons are predominantly found in the spinal cord and brainstem, but also exist in the retina and other parts of the brain. + +These neurons are critical to the inhibitory control of neuronal networks, helping to regulate excitation and maintaining neuronal stability. They play a primary role in modulating and controlling motor and sensory information within the nervous system. In general, when a glycinergic neuron fires, it releases glycine, which binds to glycine receptors on a nearby neuron. This binding causes the neuron membrane to hyperpolarize, subsequently reducing the probability of the neuron firing an action potential, which in essence dampens or inhibits the neuron from transmitting further signals. This function plays a vital role in preventing overexcitation, which may lead to neuronal damage or neurodegenerative conditions. + +Moreover, glycinergic neurons are integral to certain sensory processes and motor coordination. In the auditory system, these neurons aid in the localization of sound, and in the spinal cord, they are involved in the regulation of motor reflexes and rhythms. Any dysfunction in the glycinergic system can cause serious neurological conditions, such as hyperekplexia, characterized by increased startle responses and periodic bouts of rigidity, and some forms of chronic pain. +" DOI:10.1016/j.pneurobio.2010.04.008|DOI:10.1111/j.1399-6576.2005.00786.x|DOI:10.1042/NS20160009|DOI:10.1007/BF02740653|DOI:10.1093/brain/awx289 +419 CL:1001611 CL_1001611 "Cerebellar neurons represent a distinctive class of neurons found in the cerebellum, a crucial region of the brain that plays a pivotal role in motor control and coordination. They are the most abundant type of neuron in the human brain and play an integral part in the complex cerebellar neuronal network. + +Functionally, cerebellar neurons serve as the primary conveyors of sensory and motor information in the cerebellum. Cerebellar granule cells are a type of cerebellar neuron that receive inputs from mossy fibers originating from various parts of the central nervous system, including the spinal cord and the brainstem, processes that information, and relay motor commands to the cerebellar nuclei. Moreover, these neurons form extensive synaptic connections with Purkinje cells, the other principal neuron type in the cerebellum, thus helping to integrate and fine-tune the output signals. As such, modifications in the structure or function of cerebellar neurons often lead to disorders of balance, coordination, and motor learning. + +Cerebellar neurons also are known for their role in various cognitive functions. For example, cerebellar granule cells play various roles, including attention, language processing, and fear response." DOI:10.1523/JNEUROSCI.2759-13.2013|DOI:10.3389/fncir.2020.611841|DOI:10.1002/dneu.20875|DOI:10.12688/f1000research.15021.1|DOI:10.1016/j.neubiorev.2015.09.019 +420 CL:2000032 CL_2000032 "Peripheral nervous system (PNS) neurons, also known as peripheral nerve cells, are a key type of cell found in the PNS. The PNS includes all the nerves and ganglia outside of the brain and spinal cord. The PNS neurons transmit information between the central nervous system (CNS) and the rest of the body, playing a pivotal role in the body's communication system. + +PNS neurons are mainly responsible for relaying sensory and motor information. They help to transmit information about sensory stimuli, such as heat, touch, and pain, from the body to the CNS. This sensory function is crucial in enabling an organism to interact optimally with its environment. Additionally, these neurons mediate motor responses by transmitting signals from the CNS to muscles or glands, thereby controlling their function. + +There are three main types of PNS neurons - sensory neurons, motor neurons, and autonomic neurons. Sensory neurons convert external stimuli from the organism's environment into internal electrical impulses and carry these impulses from the sensory organs to the brain and the spinal cord. Motor neurons, conversely, carry signals from the spinal cord and brain to the muscles and glands, enabling movement and secretion respectively. Autonomic neurons, on the other hand, control involuntary functions such as heart rate, digestion, and breathing. These diverse functions underscore the critical role of PNS neurons in maintaining and regulating body functions." DOI:10.1016/B978-0-444-52902-2.00003-5|DOI:10.1177/0300985820959231|DOI:10.1038/nrn2057|DOI:10.3389/fncel.2014.00293|DOI:10.3389/fimmu.2021.679055 +421 CL:2000029 CL_2000029 "Central nervous system (CNS) neuron is a specialized cell type found within the structures of the brain and spinal cord. As a fundamental unit of the CNS, these cells are critical to its overall function to process and transmit information via electrical and chemical signals to facilitate communication between different parts of the body. + +CNS neurons are characterized by a complex structure which includes the cell body, dendrites, and the axon. The cell body houses the nucleus and other organelles essential for the cell's survival, whereas the dendrites and axon are dedicated to the facilitation of signal transduction. Dendrites serve to receive incoming signals from other neurons, while the axon is responsible for transmitting these signals to other neurons or to effector cells such as muscle or gland cells. + +Functionally, CNS neurons are critically involved in numerous aspects of human physiology and behavior. They play a vital role in processing sensory information, controlling motor function, and coordinating higher cognitive processes such as learning and memory. Moreover, these cells participate in the execution of complex tasks such as decision-making, attention, and awareness. The vast diversity and high degree of connectivity between CNS neurons give rise to an intricate network capable of processing enormous amounts of information, which forms the basis of the extraordinary computational power of the human brain. Therefore, any damage to these cells may lead to conditions such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis, emphasizing their importance in maintaining overall neurological health." DOI:10.1016/j.neuron.2015.12.008|DOI:10.1016/j.cub.2004.06.035|DOI:10.1177/1073858417703030|DOI:10.3892/ijmm.7.5.455 +422 CL:2000049 CL_2000049 "Primary motor cortex pyramidal cells (PMCPs) are a specific type of neuron found predominantly in the primary motor cortex of the brain, which holds a vital role in controlling voluntary movements. These cells are characterized by their distinct pyramidal - triangularly - shaped cell bodies, large size, and long branching dendrites that facilitate extensive interneuronal connectivity. PMCPs, along with other cortical pyramidal cells, are excitatory neurons, meaning they carry electrical impulses away from the cell body, facilitating communication between different areas of the brain and the spinal cord. + +The principal function of PMCPs revolves around motor control. PMCPs in the primary motor cortex are responsible for mapping and planning complex movements, from the intention to move to the actual execution. For example, Betz cells are a type of PMCPs that extend their long axons, collectively known as the Corticospinal Tract (CST), which descends from the cortex to the spinal cord, synapsing with neurons in the spinal cord that control muscles throughout the body. This information transmission allows PMCPs to control precise, skillful, and independent movements of both proximal and distal muscles. + +Aside from controlling voluntary movement, PMCPs contribute to motor learning and adaptation by establishing new neuronal connections and strengthening existing ones. Studies using techniques like optogenetics and two-photon imaging have revealed that PMCPs undergo significant synaptic plasticity during motor learning, indicating their role in modifying motor outputs in response to training and experience. Overall, PMCPs provide a biochemical and anatomic basis for translating thoughts into actions, an essential process for the organism's interaction with the environment." DOI:10.1038/s41586-021-03950-0|DOI:10.1093/cercor/bhw134|https://www.ncbi.nlm.nih.gov/books/NBK540976|DOI:10.1046/j.1469-7580.2001.19960699.x +423 CL:4023121 CL_4023121 "The sst chodl GABAergic cortical interneuron is a specific rare type of inhibitory neuron found within the cortex of the brain. Specifically, sst refers to somatostatin, which is a peptide hormone produced by this cell. Chodl on the other hand, refers to chondrolectin, a protein highly expressed by this particular subtype of interneurons. GABAergic denotes the neurons' use of gamma-aminobutyric acid (GABA), a prominent inhibitory neurotransmitter, playing a crucial part in reducing neuronal excitability throughout the nervous system. + +GABAergic cortical interneurons expressing both sst and chodl markers play an instrumental role in balancing excitatory neural activities. Their inherent inhibitory polarity primarily functions to fine-tune the excitatory signals facilitated by the majority of cortical neurons, the pyramidal cells. Smooth dendrites and a propensity to innervate multiple targets allow these sst chodl GABAergic interneurons to control the output of many principal neurons simultaneously. This regulation results in a balanced state of neuronal activities, preventing any possibility of excess excitations that can potentially lead to brain disorders like epilepsy. + +In a broader scope, sst expressing GABAergic cortical interneurons play a pivotal role in the higher cognitive processes. By controlling the timing and synchronization, they play an essential part in shaping the dynamic cortical network activities underlying complex brain functions, such as learning, memory, and attention. These interneurons are also likely involved in specific brain oscillatory patterns. Recent studies suggest that the dysfunction or misplacement of these interneurons can lead to neurological disorders such as schizophrenia or autism." DOI:10.1038/nn.4216|DOI:10.1016/j.neuron.2023.05.032|DOI:10.1038/s41593-019-0417-0|DOI:10.3389/fncir.2016.00076|DOI:10.1093/schbul/sbaa184 +424 CL:4023011 CL_4023011 "The lamp5 GABAergic cortical interneuron, also known as Lamp5 interneuron, is a specialized subtype of cortical interneurons predominantly found in cortical layers of the brain. These cells are principally identified by the expression of the lamp5 gene. This specific subclass of GABAergic cortical interneurons are among five subclasses recently defined for their marker gene expression, which include Sst, Pvalb, Vip, Lamp5, and Sncg. In addition, these interneurons synthesize and release gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, which gives them their GABAergic characteristic. + +Within the cortical microcircuitry, the lamp5 GABAergic cortical interneurons play crucial roles in modulating neuronal excitability and synaptic transmission. GABA release from these interneurons results in the inhibition of post-synaptic neurons, effectively controlling their activity rates and preventing unchecked excitatory responses, ultimately helping in regulating the balance between excitation and inhibition. This balance is vital for maintaining normal brain functions and its disruption often leads to neuropathological conditions, such as epilepsy and Alzheimer's disease. +" DOI:10.1016/j.cell.2020.09.057|DOI:10.1371/journal.pone.0157052|DOI:10.1007/s00401-022-02457-w|DOI:10.1038/s41467-020-18752-7 +425 CL:4023013 CL_4023013 "The corticothalamic-projecting glutamatergic cortical neuron is a specific glutamatergic neuron found primarily in the cerebral cortex of the brain. These neurons are named for their synthesis of glutamate, the most abundant excitatory neurotransmitter in the nervous system. They play a pivotal role in supporting fundamental neural processing and communication by transmitting nerve signals to the thalamus from the cortex. These signals contribute to various high-level functions such as sensation, cognition, and motor commands. + +Corticothalamic-projecting glutamatergic cortical neurons are significant components of a larger corticothalamic circuit. They receive sensory information relayed from peripheral organs and integrate the data to ensure a coordinated and appropriate behavioral response. These types of neurons project their axons to different regions of the thalamus, creating a network that is crucial for sensory processing. + +The functionality of these neurons is central to maintaining the brain's rhythmic activity, as their critical role in signal transmission affects almost all sensory experiences except for smell. Malfunction of these neurons can lead to disruption in information integration and processing, which is seen in various cognitive, neurological, and psychiatric disorders such as schizophrenia, Parkinson's disease, epilepsy, and Alzheimer’s disease." DOI:10.1152/jn.2001.86.1.1|DOI:10.1523/JNEUROSCI.4023-14.2015|DOI:10.3389/fnins.2012.00053|DOI:10.1016/j.conb.2008.09.002|DOI:10.1016/j.brainres.2017.09.014 +426 CL:4023012 CL_4023012 "The near-projecting glutamatergic cortical neuron is a critical functional unit of the mammalian cerebral cortex, predominantly found in the brain's cortical layers. This neuron employs glutamate as its principal neurotransmitter, implying its role is primarily excitatory as glutamate is the chief excitatory neurotransmitter within the mammalian central nervous system and is essential for instigating action potentials. Unlike other glutamatergic projecting neurons, these neurons project their axons over shorter distances, usually within the same region of the brain, to communicate with nearby neurons or neural circuits, giving them their 'near-projecting' nomenclature. This local propagation ability allows for fine-tuned transmission of signals, supporting the enhancement of sophisticated neural mechanisms like sensory processing, learning, and memory. + +The specific functions of near-projecting glutamatergic cortical neurons are determined by which cortical layers they are located in and which neurons are their main postsynaptic targets. As a fundamental component of the complex cortical circuitry, they act interdependently with their neighboring cells, modulating the delicately balanced excitation and inhibition system. Dysfunction of these glutamatergic neurons can contribute to neurological conditions like epilepsy, Alzheimer's, or other manifestations of neurotoxicity." DOI:10.1038/s41586-018-0654-5|DOI:10.1016/j.neuron.2015.11.002|DOI:10.1016/j.conb.2014.01.015|DOI:10.1038/nrn3586 +427 CL:4023015 CL_4023015 "The sncg GABAergic cortical interneuron belongs to a subclass of diverse interneurons that populate and function within the cerebral cortex. Predominantly found in the mammalian brain, they play a crucial role in maintaining the balance between excitation and inhibition. The naming of these interneurons follows the sncg gene they express, which stands for synuclein gamma. This specific subclass of GABAergic cortical interneurons are among five subclasses recently defined for their marker gene expression, which include Sst, Pvalb, Vip, Lamp5, and Sncg. + +Generally, GABAergic cortical interneurons utilize gamma-aminobutyric acid (GABA) as their chief neurotransmitter. GABA, a potent inhibitory neurotransmitter within the mammalian central nervous system, works by reducing neuronal excitability, thereby contributing to the overall regulation of the brain's intricate signaling network. This inhibitory function is of utmost importance, as it ensures the correct functioning of cortical networks and prevents excessive neural activity that could lead to disorders such as epilepsy. + +Sncg GABAergic cortical interneurons have a highly diverse morphology and physiology. They are categorized as 'local circuit' neurons due to their limited influencing range which typically encompasses only nearby neurons. Their roles include, but are not limited to, sensory perception, encoding behavioural state, regulating neural oscillations, coordinating network synchrony, controlling the timing of cortical information processing, and shaping synaptic plasticity. Specifically, sncg GABAergic cortical interneurons are inhibited by visual stimuli. " DOI:10.1038/s41586-018-0654-5|DOI:10.1038/s41586-022-04915-7|DOI:10.1016/j.cell.2020.09.057|DOI:10.1016/j.neuron.2021.01.003|DOI:10.1016/j.neuron.2018.10.009 +428 CL:4023016 CL_4023016 "The vip GABAergic cortical interneurons are a specific subset of inhibitory neurons found in the mammalian cerebral cortex. Named after the neuropeptide they typically release, vasoactive intestinal peptide, these neurons are also characterized by producing and releasing gamma-aminobutyric acid (GABA), which is the primary inhibitory neurotransmitter in the mammalian central nervous system. This specific subclass of GABAergic cortical interneurons are among five subclasses recently defined for their marker gene expression, which include Sst, Pvalb, Vip, Lamp5, and Sncg. These interneurons play a critical role in shaping the dynamics of neural circuitry and modulating the balance between excitation and inhibition in neuronal networks. + +Regarding their function, vip GABAergic cortical interneurons serve as integral regulators of cortical activity. They primarily target other inhibitory interneuron populations such as the somatostatin-expressing sncg GABAergic cortical interneuron and the parvalbumin-expressing pvalb GABAergic cortical interneuron. By inhibiting these neuron populations, vip GABAergic cortical interneurons indirectly promote the activity of excitatory neurons, thereby serving as key facilitators of cortical activation and plasticity. They become particularly engaged during complex cognitive tasks and sensory experiences, highlighting their role in information processing and adaptation to environmental changes. + +Furthermore, vip GABAergic interneurons have a unique feature of long-range axonal projections, allowing their influence to spread over wide cortical areas. Additionally, these cells display diversity in morphological, electrophysiological and molecular properties, indicating their multifunctional role in cortical functioning. Disruptions in the function of vip GABAergic interneurons have been associated with various neurological and psychiatric disorders, including schizophrenia and autism spectrum disorder, underscoring the importance of these cells for normal brain function." DOI:10.3389/fncel.2022.811484|DOI:10.1038/s41586-018-0654-5|DOI:10.1038/s41467-018-07162-5|DOI:10.1093/cercor/bhy227|DOI:10.1016/j.celrep.2023.112628 +429 CL:4023018 CL_4023018 "The pvalb GABAergic cortical interneuron, named for its expression of parvalbumin (pvalb) and its use of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), plays an essential role in the intricate circuitry of the brain. This specific subclass of GABAergic cortical interneurons are among five subclasses recently defined for their marker gene expression, which include Sst, Pvalb, Vip, Lamp5, and Sncg. Predominantly found within the cortex, this subset of interneurons exhibits a significant influence on the behavior of the local network due to their robust inhibitory capabilities. Sampling input from the surrounding pyramidal neurons while concomitantly providing feedback inhibitory connections makes pvalb cortical interneurons a crucial constituent of cortical homeostasis. + +Functionally, pvalb GABAergic cortical interneurons are responsible for shaping neuronal activity and facilitating precisely timed and reliable information transfer within the brain. They offer inhibitory control over the excitatory neurons they synapse, allowing these cells to temper and shape the overall neuronal firing pattern in the cortical regions, thereby promoting functional efficiency and reliability. Moreover, these interneurons, by rapidly and repetitively firing, contribute to generating brain rhythms, particularly gamma oscillations, essential for cognitive functions, like perception, attention, and memory. + +Disruptions in the function of pvalb GABAergic cortical interneurons are linked to a broad spectrum of neurological and psychiatric disorders, including epilepsy, autism, and schizophrenia, indicating their central role in maintaining cortical functionality. Moreover, the distribution, density, and interconnectedness of these complex neuronal networks may vary depending on the specific cortical region, further influencing their functionality and consequently the global neuronal output of the cortical area." DOI:10.1038/s41380-023-02153-5|DOI:10.1126/science.1255263|DOI:10.1038/s41586-018-0654-5|DOI:10.3389/fpsyt.2021.679960|DOI:10.1038/s41386-020-0778-9 +430 CL:4023042 CL_4023042 "The L6 corticothalamic-projecting glutamatergic cortical neuron, often simply referred to as L6 CT neurons, is a vital component of the complex neuronal network within the brain. It is a specific type of neuron located within the sixth layer (L6) of the neocortex, the uppermost layer of the brain, specifically dedicated to higher processes like sensory perception, spatial reasoning, and conscious thought. It is identified by its ability to release glutamate, which is the principal excitatory neurotransmitter in the central nervous system.Their role in this corticothalamic pathway marks them as crucial for relaying high-level, processed information back from the cortex to the thalamus. This information relay is pivotal for the modulation of consciousness and the integration of sensory and motor information. + +Furthermore, L6 CT neurons, through their projection of axons into the thalamus, aid in the bi-directional communication, and reciprocal influence, between the cortex and the thalamus. This is essential for the fine-tuning of sensory information from the thalamus before it is relayed to the cortex. Thus, it is implicated in a number of important functions such as the regulation and maintenance of oscillatory activity in the cortex, attentional selection of sensory stimuli, and the generation of conscious perception. Therefore, L6 corticothalamic-projecting glutamatergic cortical neurons are foundational to the normal functioning of the brain, specifically in higher-order cognitive processes and sensory integration in the neocortex." DOI:10.1523/JNEUROSCI.1325-14.2014|DOI:10.1016/j.neuron.2017.05.019|DOI:10.1016/j.neuron.2014.02.021|DOI:10.3389/fncir.2021.721186 +431 CL:4023017 CL_4023017 "Sst GABAergic cortical interneuron or somatostatin-expressing GABAergic cortical interneuron, is a type of inhibitory neuron that regulates the activity of other neurons in the cerebral cortex, specifically in the mammalian neocortex. This cell type is named after the inhibitory neurotransmitter it releases, gamma-aminobutyric acid (GABA) and the particular neuropeptide it expresses, somatostatin (sst). Sst GABAergic cortical interneurons make up around 30% of all GABAergic neurons in the cortex and play a critical role in shaping cortical network dynamics and function. This specific subclass of GABAergic cortical interneurons are among five subclasses recently defined for their marker gene expression, which include Sst, Pvalb, Vip, Lamp5, and Sncg. + +Sst GABAergic cortical interneurons are known for their diverse morphology, axonal projection pattern and electrophysiological properties, but they are most characterized by sst neuropeptide expression. Sst is a hormone that helps regulate the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-coupled somatostatin receptors. These interneurons typically make synapses onto the dendrites of excitatory pyramidal cells and other interneurons, controlling the input they receive. In doing so, they are primarily responsible for inhibiting and fine-tuning the output of cortical circuits. + +The function of sst GABAergic cortical interneurons is essential to various cognitive processes, as they play influential roles in controlling the timing and spatial aspects of information processing in the brain. For instance, these cells modulate oscillatory rhythms, a key component of cognition and perception, and help mediate long-range cortico-cortical communication. Interestingly, dysfunctions associated with this cell type have been implicated in several neurological and psychiatric disorders including schizophrenia, autism, and epilepsy. +" DOI:10.1038/s41586-018-0654-5|DOI:10.3389/fncir.2016.00048|DOI:10.1016/j.neuron.2023.05.032|DOI:10.1038/s41583-021-00443-x|DOI:10.1093/schbul/sbaa184 +432 CL:4023041 CL_4023041 "The L5 extratelencephalic projecting glutamatergic cortical neuron is a highly specialized neuron located in layer 5 (L5) of the cerebral cortex. The cerebral cortex, the outermost shell of the brain, is divided into six layers based on the types of neurons they contain and the functions they perform. L5 is known for its characteristic large pyramidal neurons, among which L5 extratelencephalic projecting glutamatergic cortical neurons reside. + +Functionally, the primary role of the L5 extratelencephalic projecting glutamatergic cortical neuron is to send signals from the cerebral cortex to other parts of the brain or body apart from the telencephalon - the largest part of the brain that encompasses both cerebral hemispheres. These neurons accomplish this task through their long axons that form connections or synapses with neurons in other subcortical regions. Notably, these neurons are glutamatergic, meaning they release the neurotransmitter glutamate, which is crucial for signaling in the brain as it is the primary excitatory neurotransmitter and plays a crucial role in neural plasticity, learning, and memory. + +The L5 extratelencephalic projecting glutamatergic cortical neuron is pivotal in carrying out complex motor activities as the signals they transmit are often directed to areas of the brain responsible for the initiation and modulation of motor functions, such as the spinal cord or the brainstem. Alterations in their structure or function can lead to various neurological disorders like autism, epilepsy, and schizophrenia." DOI:10.3389/fnsyn.2022.1006773|DOI:10.1016/j.neuron.2021.08.030|DOI:10.1093/cercor/bhx012|DOI:10.1038/s41467-020-14952-3|DOI:10.1523/JNEUROSCI.0150-18.2018 +433 CL:4023038 CL_4023038 "The L6b glutamatergic cortical neuron, also known as the Layer 6b glutamatergic neuron, is a specific subtype of neuron predominantly located in layer 6b of the cerebral cortex. This region is the deepest layer of the grey matter in the brain, containing various types of neurons. The L6b glutamatergic cortical neurons are named for their primary excitatory neurotransmitter, glutamate, which they use to transmit signals across the synapse. A key feature of L6b glutamatergic cortical neurons is their distinctive morphological and molecular characteristics. They express various genes that are not commonly found in other types of cortical neurons, illustrating their unique genetic make-up and they also have a distinct morphology, with dendrites that span across multiple layers of the cortex. These neurons are specific to mammals and play a critical role in modulating the brain's various functions including sensory perception, motor commands, spatial reasoning, conscious thought, and language. + +Functionally, L6b glutamatergic cortical neurons are heavily involved in information processing and transmission. Using glutamate as its primary neurotransmitter, these neurons can excite or stimulate other neurons, contributing to the overall activity of the cortical circuit. Their most notable role lies within their ability to communicate between cortical and subcortical structures, as the axons of L6b neurons extend out of the cortex and towards various subcortical areas, including the thalamus and cortex. Hence, these neurons can modulate the output of cortical information to these subcortical destinations." DOI:10.1016/j.celrep.2020.02.044|DOI:10.1093/cercor/bhy036|DOI:10.3389/fncel.2023.1257803|DOI:10.1093/cercor/bhs254|DOI:10.1016/j.neuron.2011.06.039 +434 CL:4023043 CL_4023043 "The L5/6 near-projecting glutamatergic neuron of the primary motor cortex, also known as the M1 layer 5/6 intratelencephalic pyramidal cell, is a subcategory of excitatory neurons primarily found in layers 5 and 6 of the primary motor cortex (M1), an area of the cerebrum responsible for executing voluntary motor functions. The term “glutamatergic” refers to these neurons releasing the neurotransmitter glutamate, which is a major excitatory neurotransmitter in the mammalian central nervous system. This function contributes to the propagation of nerve signals, playing a crucial role in learning and memory procedures. + +These specialized neurons project close to their site of origin, specifically within the telencephalon or the largest previous division of the forebrain. These near projections are primarily involved in forming intratelencephalic connections. This particular characteristic distinguishes them from the long-range projecting neurons, which can bridge distant regions of the brain. + +Functionally, the L5/6 near-projecting glutamatergic neurons play important roles in various aspects of cognitive performances, including motor control, decision making, and sensory processing. Studies have implicated these neurons in action selection and execution, due to their powerful excitatory influence on other neurons within the motor cortex and other parts of the telencephalon. Additionally, the near-projecting neurons play a significant role in the modulation of local cortical circuit dynamics, through their intra-cortical and cortico-striatal projections, further influencing both motor and cognitive functions. " DOI:10.1523/JNEUROSCI.0150-18.2018|DOI:10.1523/JNEUROSCI.1188-17.2017|DOI:10.1038/s41586-018-0642-9|DOI:10.1523/JNEUROSCI.0428-23.2023 +435 CL:4023040 CL_4023040 "The L2/3-6 intratelencephalic projecting glutamatergic cortical neurons, often referred to by the shorthand L2/3-6 IT neurons, are essential variants of the most numerous types of excitatory neurons in the cerebral cortex. These neurons are found in layers 2, 3 to 6 of the cerebral cortex and are specifically classified under the glutamatergic neurons due to their ability to release the neurotransmitter. Therefore, they are primarily involved in producing excitatory responses, which serve as a significant component in the intricate pathways of neuronal communication and information processing within the brain. + +These L2/3-6 IT neurons project intratelencephalically, implying that their axons interconnect regions within the cerebral hemispheres or between the two hemispheres, particularly to other cortical areas, the striatum, and the claustrum. This feature aids in vital brain functions such as perception, cognition, voluntary motor control, and learning. Importantly, these neurons possess a characteristic pyramidal morphology, which endows them with a high degree of connectivity to other neurons - thereby playing a crucial role in the formation and function of neural networks. + +Each specific cortical layer's glutamatergic neuron subtype bears a different function; for instance, neurons in the upper layers (L2/3) generally project to other cortical areas, ultimately assisting in the integration of sensory and motor information across diverse cortical regions. Conversely, the deeper layer neurons (L6) are associated with the modulation of thalamo-cortical input and output, in addition to projecting to the thalamus, reinforcing the complexity and bilateral communication within the cerebral cortex. Thus, the L2/3-6 intratelencephalic projecting glutamatergic cortical neuron, beyond its role as an excitatory neuron, critically influences a myriad of higher brain functions, reinforcing its importance in studying neurological processes and disorders." DOI:10.1523/JNEUROSCI.0150-18.2018|DOI:10.1038/nrn3469|DOI:10.1038/s41586-021-03813-8|DOI:10.1016/j.neuron.2018.10.032|DOI:10.1038/nn.3917 +436 CL:4023048 CL_4023048 "The L4/5 intratelencephalic projecting glutamatergic neuron of the primary motor cortex is a specific type of neuron found within layer four (L4) and layer five (L5) of the primary motor cortex in the brain, predominantly in mammals. These neurons have the unique distinction of being involved extensively with intratelencephalic projections, which refers to projections within the telencephalon, the forward part of the brain, encompassing the cerebral hemispheres that are responsible for higher cognitive functions. + +These neurons are glutamatergic, meaning they use glutamate as their primary neurotransmitter, which is involved in excitatory signaling in the nervous system. It plays a fundamental role in synaptic plasticity, a process that is significant for memory function and learning. Hence, these neurons are essential components accounting for cognitive ability, memory functions, and learning progression. It is also worth noting that disturbances in glutamatergic neurotransmission can be linked to several neurological and psychiatric disorders. + +On a functional level, the L4/5 intratelencephalic projecting glutamatergic neurons predominantly contribute to the communication between different regions of the telencephalon. The various connections these neurons form play a key role in integrating sensory stimuli with motor responses, which is critical for successful interaction with the environment. By connecting different regions within the telencephalon, these neurons facilitate complex cognitive processing, thereby playing a pivotal role in voluntary movement, motor learning, and decision-making processes." DOI:10.1038/nn.3917|DOI:10.1093/cercor/bhx012|DOI:10.1038/s41586-021-03950-0|DOI:10.3389/fpsyt.2018.00767 +437 CL:4023051 CL_4023051 "Vascular leptomeningeal cells (VLMCs) are specialized fibroblasts that form part of the framework of the central nervous system, specifically within the leptomeninges. The leptomeninges are the two innermost layers of the meninges, namely the arachnoid mater and pia mater, which cover the brain and spinal cord. These critical structures are the site of cerebrospinal fluid (CSF) circulation. VLMCs are structured around the blood vessels nestled in these tissues, hence the term 'vascular'. + +VLMCs have several key functions related to brain physiology, cerebrospinal fluid dynamics, and immune responses. Firstly, they play a pivotal role in regulating water and ion exchange between the cerebrospinal fluid and the brain parenchyma, contributing to the homeostatic balance of the central nervous system. Additionally, these cells actively contribute to the formation and maintenance of the blood-brain barrier and blood-CSF barrier, both of which are critical for protecting the brain from harmful substances." DOI:10.1038/nature25739|DOI:10.1016/j.jneuroim.2021.577727|DOI:10.1016/j.neuron.2023.09.002|DOI:10.1016/j.cell.2018.06.021 +438 CL:4023050 CL_4023050 "The L6 intratelencephalic projecting glutamatergic neuron of the primary motor cortex is a specialized neuron situated in layer 6 (L6) of the primary motor cortex, a region of the brain that enables voluntary muscle control, planning of movements, and execution of complex motor tasks. The word 'intratelencephalic' denotes its pattern of connectivity, projecting within the telencephalon, the anterior part of the brain which contains both the cerebral cortex and subcortical structures. These neurons are classified as glutamatergic, as they use glutamate as their main excitatory neurotransmitter. Glutamate is a key player in mediating excitatory synapses in the mammalian central nervous system. Morphologically, these untufted neurons have short apical dendrites and with fewer branches compared to other neurons. + +The L6 intratelencephalic projecting neurons play a critical role in motor function and cognitive processes. By releasing glutamate, they stimulate other neurons to which it is connected, directly impacting processes of memory, learning, and synaptic plasticity. The glutamatergic neurotransmission from these neurons shapes the output of the intrinsic cortical microcircuitry and its interaction with other brain regions, subsequently influencing the timing, coordination, and strength of motor commands. + +Functionally, the L6 intratelencephalic projecting neurons integrate and transmit the afferent signals coming from the cortical layers above, particularly from the apical dendrites of the pyramidal neurons in layers 2 and 3. As the deepest layer in the six-layered neocortex, L6 contributes extensively to the feedback circuitry, both locally and across distal cortical areas. Despite the limited knowledge available on specific L6 neuron subypes owing to their heterogeneity, it is clear that L6 intratelencephalic projecting glutamatergic neurons serve as crucial components in the cortex's role as the canonical center for sensorimotor integration and cognition. " DOI:10.1523/JNEUROSCI.0150-18.2018|DOI:10.1523/JNEUROSCI.2254-10.2010|DOI:10.3389/neuro.04.003.2010|DOI:10.1093/cercor/bhs254|DOI:10.3389/fnana.2010.00013 +439 CL:4023056 CL_4023056 "Vascular leptomeningeal cells (Mmus) refer to specific types of cells located within the vasculature system of the leptomeninges of Mus musculus, or the common house mouse. These cells function by enveloping capillaries and microvessels and act as integral components of the blood-brain barrier (BBB). + +Vascular leptomeningeal cells contribute to maintaining homeostasis within the cerebral microenvironment. By regulating the diameter of the blood vessels, they control cerebral blood flow and ensure proper oxygen and nutrient supply to the brain tissue. Additionally, these cells are involved in the regulation of immune responses in the central nervous system as they help in controlling the passage of immune cells through the BBB. They also participate in several angiogenesis processes, which involves the formation of new blood vessels from pre-existing ones. + +Notably, vascular leptomeningeal cells have a direct relationship with certain neurological pathologies. Research suggests that alterations or damage to these cells may contribute to the onset and progression of neurological disorders, including stroke, Alzheimer’s disease, and multiple sclerosis. " DOI:10.1038/nature25739|DOI:10.1124/dmd.112.050344|DOI:10.1016/j.neuron.2023.09.002|DOI:10.1016/j.jneuroim.2021.577727|DOI:10.1007/BF00296738 +440 CL:4023057 CL_4023057 "The cerebellar inhibitory GABAergic interneuron is a specialized type of neuron located within the cerebellum, a region of the brain that plays a vital role in motor control and coordination. These cells are classified as interneurons because they facilitate communication between sensory neurons and motor neurons. As their name suggests, these interneurons primarily utilize gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter within the mammalian central nervous system. + +Functionally, cerebellar inhibitory GABAergic interneurons play a crucial role in modulating the overall output of the cerebellum through inhibiting the activity of other neurons. Specifically, when a GABAergic interneuron releases GABA, it binds to GABA receptors on the postsynaptic neurons, making them less likely to fire. This inhibition function helps to maintain balance in the cerebellar neuronal networks and controls the fine-tuning of motor commands, contributing to the smooth and precise execution of movements. + +The cerebellar inhibitory GABAergic interneurons can be further subdivided based on their morphological and physiological characteristics, including cerebellum basket cells, cerebellar stellate cells, and cerebellar Golgi cells, each of which has a unique role within the cerebellar networks. For instance, cerebellum basket cells mainly interact with Purkinje cells – the primary output neurons of the cerebellar cortex, while cerebellar stellate cells modulate the synaptic input to these Purkinje cells. Cerebellar Golgi cells, on the other hand, regulate the activity of granule cells, the most numerous neurons in the cerebellum. Despite these differences, all these subsets of GABAergic interneurons share the common feature and central role of inhibiting neuronal activity, thereby contributing critically to the overall function of the cerebellum." DOI:10.1038/nrn2188|DOI:10.1523/JNEUROSCI.3656-06.2006|DOI:10.3389/fncir.2012.00123|DOI:10.1007/s12311-008-0079-z|DOI:10.1007/s00418-023-02251-z +441 CL:4023058 CL_4023058 "The mesothelial fibroblast of the leptomeninx is a specialized type of cell typically located in the leptomeninx or leptomeninges, a portion of meninges consisting of the arachnoid mater and pia mater. The meninges are protective layers surrounding the brain and spinal cord, with the leptomeninx being the delicate inner two layers. These fibroblasts play a critical role within the central nervous system, contributing to the structure, maintenance, and overall functionality of the leptomeninx. + +Generally, mesothelial fibroblasts are characterized by their spindle-shaped morphology and their function, which pertains primarily to the production of the extracellular matrix (ECM). The ECM provides structural support, contributes to tissue repair, and influences various cellular activities such as growth and differentiation. Mesothelial fibroblasts are highly involved in collagen production, which is an integral protein in the ECM. Consequently, these cells play a vital role in physical and biological scaffolding and in maintaining the stability and resilience of the leptomeninges. + +Under pathological conditions, mesothelial fibroblasts of the leptomeninx may undergo changes and contribute to disease progression. For example, in cases of meningitis, these cells can mount an inflammatory response to help fight off the infection. When the ECM is damaged due to trauma or disease, mesothelial fibroblasts of the leptomeninx can also become activated, migrating to the site of injury to aid in tissue repair and remodeling. Therefore, the mesothelial fibroblasts of the leptomeninx reflect a crucial multidimensional role in both normal physiological and disease-related processes within the leptomeninges of the central nervous system." DOI:10.1016/j.neuron.2023.09.002|DOI:10.1126/science.adc8810|DOI:10.3892/mmr.2016.5411|DOI:10.1371/journal.pone.0080463|DOI:10.1148/rg.230039 +442 CL:4023065 CL_4023065 "The meis2 expressing cortical GABAergic cell is a unique and specialized type of neuron found within the complex architecture of the cerebral cortex. Specifically, these neurons originate from a region bordering the pallium and subpallium. Meis2 refers to the gene that codes for the Meis homeobox2 protein, which is a crucial transcription factor that regulates neural development. Most importantly, the GABAergic characteristic of these cells refers to their function in relation to the release of the neurotransmitter gamma-aminobutyric acid (GABA), which carries inhibitory signals to help maintain stable and controlled communication between neurons. + +One of the essential roles that the meis2 expressing cortical GABAergic cell plays in the organism is in establishing a balance between excitation and inhibition in neuronal signaling. The primary neurotransmitter that this cell synthesizes and releases is GABA, the main inhibitory neurotransmitter in the mammalian central nervous system. It acts to reduce neuronal excitability and prevents over-firing of neurons, effectively preventing excessive neuronal activity that could lead to seizures or overstimulation. By countering excessive excitatory signals, GABAergic cells work to stabilize the intricate dynamics of the brain and maintain physiological homeostasis." DOI:10.1038/s41586-018-0654-5|DOI:10.1038/ncomms14219|DOI:10.1242/dev.200035|DOI:10.1016/j.stemcr.2018.03.010|DOI:10.1038/s41598-022-21496-7 +443 CL:0011103 CL_0011103 "Sympathetic neurons are a distinct class of neurons that are an integral part of the autonomic nervous system, specifically within the sympathetic division. They play a critical role in the body's 'fight or flight' responses and are primarily involved in regulating involuntary physiological processes, such as heart rate, blood pressure, body temperature, and metabolic processes. These neurons are essential for homeostatic mechanisms, working to ensure a balanced state is maintained within the body amidst changing environments. + +Structurally, sympathetic neurons are characterized by their relatively long axons, which allow them to relay signals from the central nervous system to various peripheral organs and tissues. They typically originate within the spinal cord's thoracic and lumbar regions, extending their axons to connect with various targets, including cardiac muscle, smooth muscle, and glands. These neurons often utilize noradrenaline (norepinephrine) as a neurotransmitter, which binds to adrenergic receptors on the target cells to exert their effects. + +Functionally, the sympathetic neurons help the body respond to stressful or threatening situations. When activated, they provoke a cascade of processes that ready the body for quick action. This includes accelerating the heart rate, dilating the pupils, slowing digestion, and increasing blood flow to muscles. Conversely, when the threat has passed, they encourage a return to normalcy by inhibiting these same processes. Beyond this 'fight or flight' response, sympathetic neurons also function to help regulate body temperature by inducing sweating or shivering, influence the dilation of blood vessels to control blood pressure, and can stimulate the release of glucose from the liver to provide energy. Overall, sympathetic neurons are key mediators of the body's response to various internal and external stimuli, maintaining homeostasis and preparing the body for diverse challenges." DOI:10.1146/annurev.neuro.22.1.541|DOI:10.1038/s41583-021-00523-y|DOI:10.1023/A:1009889922985|DOI:10.1161/HYPERTENSIONAHA.111.00633|DOI:10.1152/physrev.00005.2023 +444 CL:0013000 CL_0013000 "Forebrain radial glial cells are specialized cells in the central nervous system known for their essential role in the formation of the brain during neurodevelopment. These cells are primarily located in the ventricular zone of the developing forebrain, which is composed of the cerebrum and the diencephalon. Radial glial cells are named for their unique morphology, specifically their elongated cell bodies, which extend radially from the ventricular surface to the pial surface, acting as a scaffold for newborn neurons to migrate along during the development of the brain. + +Functionally, forebrain radial glial cells serve as both progenitor cells and guide cells for neurons. They proliferate to increase their population and produce neurons or glial cells through asymmetric division, contributing to the complexity and diversity of cell types in the brain. During neurogenesis, an important process in brain development, radial glial cells provide physical and biochemical guidance to newborn neurons, helping them migrate from their birthplace in the ventricular zone to their final destination in the cortical plate. + +Furthermore, forebrain radial glial cells play a critical role in the formation of the cerebral cortex layers through their interaction with newborn neurons. They are involved in the establishment of the six-layered architecture of the cerebral cortex, crucial to higher cognitive functions, sensory processing, and control of motor behavior. After completing their roles in neurogenesis and the formation of cortical layers, most radial glial cells transform into astrocytes or oligodendrocytes, the main glial cell types in the mature brain. Thus, from their contribution to the proliferation and differentiation of neurons to the establishment of cortical layering, forebrain radial glial cells perform several fundamental roles in brain development." DOI:10.1002/glia.10244|DOI:10.1016/S0070-2153(05)69004-7|DOI:10.1038/35055553|DOI:10.1016/j.biocel.2013.11.013|DOI:10.1016/j.neuron.2016.09.005 +445 CL:0000057 CL_0000057 "Fibroblasts are a type of mesenchymal cell which constitute the most common cells of connective tissues in mammals. They maintain the structural integrity of connective tissues by continuously secreting precursors of the extracellular matrix. The matrix keeps tissues structurally sound, offers a scaffolding for cells and serves as a medium for the exchange of nutrients and waste between cells. Fibroblasts play a critical role in wound healing as well, where they migrate towards the site of injury and produce a new extracellular matrix. + +Fibroblasts are resilient and versatile, revealing diverse variation in their shape and size, often reflecting their function and location in the body. They exhibit a spindle-like morphology, with a flat and elliptical nucleus located at the center. Characteristically, fibroblasts contain a large rough endoplasmic reticulum and abundant Golgi apparatus to facilitate protein synthesis for the extracellular matrix. + +In addition to producing the extracellular matrix, fibroblasts possess the ability to differentiate into other cell types, showcasing their importance in tissue repair. For instance, when a tissue injury occurs, fibroblasts can transform into myofibroblasts, cells with features of both fibroblasts and smooth muscle cells, to aid in the wound healing process. They also play a role in immune response, as they can present antigens to T-cells and produce a variety of cytokines and chemokines. " DOI:10.1016/j.cell.2021.06.024|DOI:10.1038/s41536-021-00153-z|DOI:10.3389/fphar.2014.00123|DOI:10.1016/S0074-7696(07)57004-X|DOI:10.1038/s41577-021-00540-z +446 CL:0000005 CL_0000005 "Fibroblast neural crest-derived cells are a specific type of cells originating from the neural crest. The neural crest is a transient structure during embryonic development from which multipotent cells arise that migrate throughout the body to give rise to a wide array of cell types, including fibroblasts. + +Fibroblast neural crest-derived cells are of mesodermal origin and play a critical role in various biological processes. The differentiation of these cells contributes in the formation of diverse anatomical structures in the vertebrate body, particularly the peripheral nervous system, the facial skeleton, and certain vascular tissues. Due to their migratory nature, fibroblasts can move to specific areas of the body where they participate in healing mechanisms through production of the extracellular matrix and collagen, thereby aiding in wound healing processes and tissue repair. + +Furthermore, these cells serve a significant role within the skin, forming the dermis layer and contributing to skin homeostasis and repair. These cells are also vital in the development of the craniofacial cartilage and bone. Given their broad developmental potential, fibroblast neural crest-derived cells have been the focus of much scientific research, particularly in the fields of developmental biology and regenerative medicine. " DOI:10.1242/dev.01429|DOI:10.1016/j.ydbio.2011.12.042|DOI:10.1002/wsbm.1224|DOI:10.1038/cr.2012.11|DOI:10.1016/j.ydbio.2018.05.011 +447 CL:0000062 CL_0000062 "Osteoblasts are a type of bone cell primarily responsible for bone formation. Osteoblasts are derived from mesenchymal stem cells, which differentiate into osteoblasts under the influence of various growth factors, including bone morphogenetic proteins (BMPs). These multipotent cells play a critical role in the bone formation process known as ossification. + +The primary function of osteoblasts is to synthesize and deposit bone matrix, a mixture of organic substances and inorganic materials. This included producing a mix of collagen and non-collagenous proteins, which they secrete to create the organic portion of the extracellular bone matrix. The osteoblasts also initiate the mineralization process by depositing calcium and phosphate ions onto this organic matrix, generating a material that is incredibly strong and resilient, which we recognize as bone. + +Furthermore, osteoblasts are intricately involved in bone remodeling. They communicate with other specialized bone cells, like osteoclasts (involved in bone resorption) and osteocytes (derived from osteoblasts and important for bone maintenance), helping to maintain skeletal health and homeostasis. Dysregulation of osteoblast function can lead to various bone diseases, illustrating the importance of these cells in skeletal health and development." DOI:10.3390/ijms19020360|DOI:10.1038/s41580-020-00279-w|DOI:10.1089/ten.teb.2016.0454|DOI:10.1038/s41574-019-0246-y|DOI:10.1038/nrm3254 +448 CL:0000186 CL_0000186 "Myofibroblasts are specialized cells predominantly found within the connective tissues of the body, most notably in areas of injury or wound healing. They carry out a crucial role in many biological processes, including tissue repair and fibrosis, wound contraction, and organogenesis. Though similar to fibroblasts, myofibroblasts can be differentiated by their unique morphological features and the presence of specialized protein bundles called stress fibers. + +Myofibroblasts originate from several cell types based on the physiological condition or the injury context, including local fibroblasts, epithelial cells, and endothelial cells, shedding light onto their plasticity. Upon tissue injury or wound creation, myofibroblasts activate and undergo a transformation process whereby they develop contractile features. They express a type of protein called alpha-smooth muscle actin (α-SMA), allowing them to contract and aid in wound closure. These cells also produce extracellular matrix (ECM) components, primarily collagen, to support and provide structural integrity to the healing tissue. + +However, while myofibroblasts play a critical role in normal wound healing, their function can be detrimental in certain pathological conditions. For instance, in chronic diseases such as fibrosis or scarring, the extended presence or overactivity of myofibroblasts can lead to the excessive production of ECM and fibrous tissues, leading to hardened, rigid tissues and organ dysfunction. " DOI:10.1038/nrm809|DOI:10.3390/biom11081095|DOI:10.2147/CCID.S50046|DOI:10.7860/JCDR/2014/7820.4231|DOI:10.1002/path.4104 +449 CL:0000448 CL_0000448 "White fat cells, also known as white adipocytes, are cells found primarily in the white adipose tissue, a specialized type of connective tissue that functions as the major storage site for energy in the form of lipids. This type of adipose cell is characterized by its large droplets of liquid fat, called triglycerides, which almost completely fill the cell pushing the nucleus and other organelles to the periphery. They appear white or yellowish in color due to their high cytoplasm lipid content. + +White fat cells are involved in lipogenesis, the metabolic process where excess glucose and other energy-rich compounds are converted into neutral fats for storage. Conversely, these cells also play a pivotal role in lipolysis, the breakdown of triglycerides to release glycerol and fatty acids, when required by the body. Moreover, these cells act as thermal insulators, helping to maintain the body's temperature. + +Importantly, white fat cells are crucial for the proper functioning of numerous physiological processes including appetite regulation, inflammatory response, and immunity. They are also known to secrete various hormones and cytokines, such as leptin and adiponectin, which are instrumental in regulating metabolic activities and maintaining overall metabolic homeostasis. Dysregulation of these cells, along with an accumulation of excess white fat, has been linked to several health issues including obesity, metabolic syndrome, and type 2 diabetes." DOI:10.1038/s41574-021-00471-8|DOI:10.1146/annurev.nutr.27.061406.093734|DOI:10.1038/s42255-021-00493-6|DOI:10.1016/j.arcmed.2008.09.005|DOI:10.1038/s41574-019-0230-6 +450 CL:0000432 CL_0000432 "Reticular cells are a category of stellate or star-shaped cells that are found largely within the reticular connective tissue. This type of tissue forms the framework or stroma of several organs, predominantly among the lymph nodes, spleen, and bone marrow, which are components of the immune system. The primary role of reticular cells is to provide infrastructure by producing the fibrous network that provides structural support to these organs and contribute to the formation of a specialized environment crucial for the development and maturation of immune cells. + +Reticular cells are also key players in immune regulation and homeostasis. Reticular cells serve as antigen-presenting cells, a behavior which alerts other immune cells, such as lymphocytes, to the presence of the foreign substance, instigating an immune response. This makes reticular cells crucial in the body's defense against diseases and infections. Additionally, reticular cells actively contribute to the nurturing of developing lymphocytes. They excrete several substances including cytokines, which are regulatory proteins that influence cell development and response to various stimuli. This feature is crucial in the bone marrow where reticular cells, along with others, form part of a unique micro-environment that enables the maturation of B lymphocytes, a type of cell responsible for producing antibodies. " DOI:10.1038/nri3846|DOI:10.1093/ptj/79.3.308|DOI:10.4049/jimmunol.1402520|DOI:10.1084/jem.20040254|DOI:10.1038/ni.2965 +451 CL:0000449 CL_0000449 "Brown fat cells, also known as brown adipocytes, form a type of adipose tissue that regulates energy by thermogenesis (heat production). These cells are rich in mitochondria, which lends them their characteristic brown colouring. Mitochondria are crucial to the brown fat cell's function since they contain an integral protein called uncoupling protein 1 (UCP1). This protein permits protons to leak across the mitochondrial inner membrane, disrupting the usual pathway of ATP production. Instead of generating ATP, the energy derived from glucose and fatty acids is dissipated as heat. This unique function makes brown fat cells an important biological tool for regulating body temperature, especially in infants and hibernating animals. + +While historically believed to be primarily relevant in newborns, recent findings highlight a role of brown fat cells in adults as well. They provide significant health benefits by metabolising excess glucose in the body and burning unwanted fat, and thereby raising the possibilities of using brown fat cells therapeutically for conditions like obesity or diabetes. Furthermore, stimulation of brown fat activity in adults is linked with improved overall metabolic health and lower risk of metabolic syndrome. " DOI:10.4161/adip.18951|DOI:10.1042/BJ20130457|DOI:10.1074/jbc.M000547200|DOI:10.1007/164_2018_118|DOI:10.1097/MED.0b013e328337a81f +452 CL:0000499 CL_0000499 "Stromal cells constitute a significant portion of the structural cellular milieu (stroma) that supports the function of parenchymal (functional) cells within an organ. The stroma is the connective, supportive framework of biological tissues with various functions depending on the specific organ and cell type. Stromal cells, derived from the mesenchymal lineage, play crucial roles in creating, maintaining, and repairing the tissue microenvironment in virtually all mammalian organs, making these cells indispensable to biological function. + +Additionally, stromal cells secrete growth factors, cytokines, and extracellular matrix (ECM) molecules to constitute an interactive cellular network and ensure an optimal environment for the functional cells. Beyond mere structural support, these cells are instrumental in wound healing, inflammation, and maintaining tissue integrity. They may also influence the behavior of other cell types through direct cell-cell interactions or paracrine signaling. + +Clinically and in research, stromal cells often draw attention due to their interaction with tumors in the cancer microenvironment. Over the past years, the role of stromal cells as facilitators of tumor growth and metastasis has been recognized increasingly. They contribute to cancer progression not only by modulating the ECM but also through the secretion of various bioactive molecules and interacting with immune cells, thereby influencing the immunologic responses to tumors. " "DOI:10.1038/s41536-019-0083-6|DOI:10.1634/stemcells.2007-0637|DOI:10.1186/s13058-016-0740-2 +|DOI:10.3389/fcell.2020.555378|DOI:10.1038/nri2588" +453 CL:0000503 CL_0000503 "Theca cells are specialized stromal cells found within the ovaries, more specifically in the follicles that house and nurture the developing ovum. They exist in two forms: theca interna cells and theca externa cells, both playing significant roles in ovarian function and the reproductive system as a whole. Found in all mammalian species, these cells allow intricate processes like ovulation and hormonal control to function seamlessly. + +Theca interna cells are highly vascularized and specialized to produce androgens, specifically androstenedione, a precursor to estradiol. When the follicle-stimulating hormone (FSH) stimulates granulosa cells to produce aromatase, this enzyme then converts the androgens into estrogens. Consequently, the hormonal interaction between theca interna cells and granulosa cells supports the production of estrogen necessary for the reproductive cycle. + +Theca externa cells, on the other hand, are mechanically supportive cells. They form an outer protective layer around the follicle. While they do not directly influence hormone production, they play an essential role in structural integrity and act in concert with the granulosa and theca interna cells during the rupture of the mature ovarian follicle, releasing the egg for potential fertilization. Simultaneously, these cells participate in the formation of the corpus luteum, which secretes progesterone to prepare the uterus for potential implantation." DOI:10.1038/ncomms7934|DOI:10.1016/j.biocel.2005.01.016|DOI:10.1210/er.2017-00164|DOI:10.1097/CM9.0000000000000850|DOI:10.1155/2015/925691 +454 CL:0000632 CL_0000632 "Hepatic stellate cells (HSCs) are a unique cell type found in the liver, residing in the space between the sinusoidal endothelial cells and the hepatocytes, known as the space of Disse. Despite constituting only 5-8% of the total number of liver cells, they play a significant role in the maintenance of liver health. They have a star-shaped (stellate) structure, hence their name and their principal function is the storage of vitamin A in their cytoplasm as retinyl esters. + +HSCs become highly active when the liver is damaged or diseased. They play a crucial role in the liver's response to injury and wound-healing process, converging into myofibroblasts, the cells responsible for scar tissue formation (fibrosis). They are also involved in maintaining the extracellular matrix balance by producing matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), which break down and inhibit the breakdown of collagen respectively. HSCs also play a part in regulating blood flow through the liver’s blood vessels, help fight infections, and are involved in interactions among different types of liver cells. Recent research has implicated them in regulating liver regeneration and in the development of liver cancer. " DOI:10.1172/JCI66369|DOI:10.1016/S0083-6729(06)75006-3|DOI:10.1038/s41598-019-43759-6|DOI:10.1002/hep4.1628 +455 CL:0000650 CL_0000650 "Mesangial cells are specialized cells that primarily reside in the middle layer, or mesangium, of the renal glomerulus within the kidney. The primary function of mesangial cells is to maintain the structural stability and function of the glomerular capillary tuft. They achieve this by providing structural support to the capillary loops, controlling the surface area available for filtration in response to physiological alterations in blood pressure, and removing trapped material and proteins from the basement membrane, which otherwise could cause damage. Moreover, mesangial cells regulate the glomerular blood flow by contracting and relaxing, similar to smooth muscle cells. They also synthesize extracellular matrix components, including collagen and fibronectin, that form the structural framework of the glomerulus. + +Beyond their structural and regulatory roles, mesangial cells are involved in several immunologic functions. They express a variety of receptors that can recognize immune complexes and subsequently mediate an inflammatory reaction. Their role in the immune response includes the production of a variety of cytokines and growth factors, which make them a key cellular component in the progression of several renal diseases. " DOI:10.1038/s41581-021-00474-8|DOI:10.3389/fmed.2021.740527|DOI:10.1681/ASN.2019070724|DOI:10.1007/BF00180754|DOI:10.3389/fimmu.2022.1063497 +456 CL:0000669 CL_0000669 "Pericytes, also known as Rouget cells, are a type of cell embedded in the wall of small blood vessels such as capillaries and venules. Not only do these cells share a basement membrane with endothelial cells, but they also have a direct physical contact with them, forming the blood-brain and blood-retinal barrier. They are an essential component of the neurovascular unit, a structure critical for maintaining brain homeostasis and a consistent neural microenvironment. + +Pericytes play a crucial role in the regulation of microvascular blood flow and permeability. They dynamically respond to changes in blood flow and can relax or contract like smooth muscle cells, thereby controlling capillary diameter and blood flow to the tissues. Moreover, pericytes contribute significantly to the regulation of endothelial cell proliferation and migration, implying their vital role in angiogenesis and the stability of blood vessels. Their ability to differentiate into multiple cell types, including fibroblasts, macrophages, and smooth muscle cells, reveals their importance in tissue repair and remodeling. + +Furthermore, pericytes have demonstrated functions in regulating immune and inflammatory responses. Pericytes also collaborate with endothelial cells in preserving the integrity of the blood-brain barrier, thus protecting the central nervous system from potential damage due to harmful substances and pathogens. " DOI:10.3389/fncel.2019.00282|DOI:10.1016/j.cjtee.2020.02.006|DOI:10.1007/978-1-60761-938-3_2|DOI:10.1177/0271678X15610340|DOI:10.3390/biomedicines11020600 +457 CL:0002132 CL_0002132 Stromal cells of the ovary, also known as ovarian stromal cells, form a significant portion of the ovarian tissue. They are non-epithelial cells that primarily make up the supportive or connective tissue—similar to the stroma of other organs—in the ovaries. These cells play vital roles in folliculogenesis, including in the activation of primordial follicles and in the differentiation of theca cells. They are crucial for maintaining the structure, function, and overall health of the ovaries. In addition to roles in hormone production and follicle maturation, stromal cells of the ovary play a role in ovarian aging and age-related diseases such as ovarian cancer. They participate in cell-to-cell communication with oocyte and other ovarian cell types through gap junctions and paracrine signaling and help maintain the ovarian microenvironment. DOI:10.1530/REP-19-0501|DOI:10.1371/journal.pone.0205494|DOI:10.1038/s42003-022-04384-8|DOI:10.1017/CBO9780511921896.037|DOI:10.1186/s13578-017-0163-5 +458 CL:0002241 CL_0002241 "Pulmonary interstitial fibroblasts, or lung fibroblasts, are a specific type of cell located within the lungs. They are predominantly located in the connective tissue or interstitial space of the lung that is in close proximity to the alveolar epithelium and pulmonary capillaries. These cells play a crucial role in maintaining lung structure and function through the synthesis and remodeling of the extracellular matrix, which provides structural support to the lung tissues. + +These cells ensure effective gas exchange by providing a scaffold for the epithelial structure. In addition to providing support, the extracellular matrix acts as a binding site for various molecules that can directly influence cell behavior and the local microenvironment. Fibroblasts not only secrete the extracellular matrix themselves but also have the capacity to remodel the matrix by producing matrix metalloproteinases (MMPs). This ability of synthesis and degradation makes fibroblasts essential for normal lung homeostasis and repair following lung injury. + +Under pathological conditions such as pulmonary fibrosis, the function of pulmonary interstitial fibroblasts becomes deregulated. They become overly active and produce excess extracellular matrix, notably collagen, resulting in the thickening and stiffening of lung tissues that compromise its function. Furthermore, these cells can transform into myofibroblasts, cells that are more active in producing matrix proteins and contribute to scar formation or fibrosis. Understanding the biology and regulation of pulmonary interstitial fibroblasts is thus essential for devising therapeutic strategies for diseases characterized by abnormal tissue remodeling and fibrosis, such as idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease (COPD)." DOI:10.1002/sctm.20-0526|DOI:10.1016/j.heliyon.2023.e19428|DOI:10.3390/ijms20061461|DOI:10.1164/rccm.200706-929OC|DOI:10.1513/AnnalsATS.201605-341AW +459 CL:0002335 CL_0002335 "Brown preadipocytes are a type of precursor cell vital in the development and function of brown adipose tissue (BAT). These immature cells are capable of proliferating and differentiating into mature brown adipocytes. Brown preadipocytes are distinct in their thermogenic potential due to their capacity to become brown adipocytes, known for heat generation, which is especially crucial in maintaining body temperature in cold environments. These cells are primarily found in mammalian organisms, particularly those that need to adapt to lower temperatures. + +Functionally, brown preadipocytes play an instrumental role in the process of adipogenesis, which is the formation of adipose (fat-storing) tissue. When subjected to specific stimuli or under the appropriate conditions, these cells can differentiate into mature brown adipocytes. These adipocytes contain a high volume of mitochondria and have the unique ability to burn energy and release it as heat, a process known as thermogenesis. This unique energy expenditure process is chiefly due to the presence of a mitochondrial protein called uncoupling protein 1 (UCP1). + +The study of brown preadipocytes and their subsequent conversion into mature brown adipocytes is of significant interest in tackling obesity and related metabolic disorders. Since their thermogenic activity contributes to energy expenditure, they provide an attractive target for approaches looking to increase energy consumption in the body. Emerging research suggests that enhancing the number or activity of brown adipocytes could be a possible avenue for therapeutic interventions against obesity and type 2 diabetes. " DOI:10.1152/physrev.00015.2003|DOI:10.3109/07853890.2010.535557|DOI:10.1038/nrendo.2016.136|DOI:10.3389/fphys.2015.00004 +460 CL:0002334 CL_0002334 "A preadipocyte is an immature precursor to adipocytes, which are specialized cells primarily tasked with the storage of energy in the form of lipids, making them key in metabolic regulation and overall energy homeostasis. Preadipocytes are present in the stromal vascular fraction of adipose tissues and can be identified by their fibroblastic morphology and the expression of specific markers such as Pref-1, CD24, CD34, and CD29. + +The primary function of preadipocytes is to proliferate and differentiate into mature adipocytes upon receiving the appropriate physiological and hormonal stimuli. The process of adipogenesis, involving the differentiation of preadipocytes, is controlled by a complex network of transcription factors, including the peroxisome proliferator-activated receptor gamma (PPARγ) and members of the CCAAT/enhancer-binding proteins (C/EBPs) family. Through adipogenesis, preadipocytes contribute to the body's energy storage and insulation capabilities and act as a buffer to control the levels of free fatty acids in the bloodstream. When the energy balance of the body alters, for example during fasting or overnutrition, preadipocytes can respond by modulating adipogenic differentiation and lipid storage, illustrating their dynamic role in metabolic regulation. + +Additionally, research has shown that preadipocytes also contribute to endocrine function. They produce and secrete several adipokines such as leptin, adiponectin, and resistin. These adipokines impact a variety of physiological processes, including appetite regulation, insulin sensitivity, inflammation, and immune responses. Dysregulation of preadipocyte function and adipogenesis is associated with obesity and related metabolic disorders, such as type 2 diabetes and cardiovascular disease." DOI:10.3389/fendo.2023.1199589|DOI:10.1007/s12015-017-9774-9|DOI:10.1128/MCB.01344-13|DOI:10.1186/s12950-018-0185-8 +461 CL:0002363 CL_0002363 "Keratocytes, also referred to as corneal fibroblasts, are specific cell types that primarily reside in the stromal layer of the cornea. Highly specialized, these cells play an essential role in the maintenance and repair of corneal tissue, thereby contributing to clear, distortion-free vision. As fibroblasts, their function often involves synthesis and secretion of the extracellular matrix, which gives the corneal stroma its structural integrity. + +Keratocytes are primarily responsible for the synthesis of collagen and proteoglycans, the principal components of the stromal extracellular matrix (ECM). The high optical clarity of the cornea is largely attributed to the unique arrangement of collagen fibrils, and keratocytes play a fundamental role in maintaining this arrangement. In response to corneal wounds or injuries, the keratocytes near the wound site become activated and undergo a transformation into a specialized phenotype, often referred to as repair keratocytes or activated keratocytes. + +During corneal repair, these activated keratocytes proliferate and migrate to the wound site, where they differentiate into myofibroblasts. Myofibroblasts play a significant role in wound contraction and synthesis of an alternative ECM required for wound closure. However, the overzealous activity of myofibroblasts can lead to corneal haze, a condition that impairs vision, and numerous studies suggest that optimal wound healing involves a delicate balance between repair and the pro-scar actions of myofibroblasts. " DOI:10.1016/j.exer.2020.108228|DOI:10.1016/j.biocel.2006.03.010|DOI:10.1111/j.1463-5224.2009.00742.x|DOI:10.1038/s41598-019-53123-3 +462 CL:0002410 CL_0002410 "Pancreatic stellate cells, also known as PSCs, are a specific type of cell comprising 4-7% the pancreas, specifically the exocrine glandular tissue. In their quiescent state, these cells are characterized by a star-like appearance with long cytoplasmic processes, and store vitamin A droplets in their cytoplasm. The primary roles of pancreatic stellate cells are related to the production, degradation, and reorganization of the extracellular matrix in the pancreas. When activated by injury or stress, they transform into myofibroblast-like cells, beginning to proliferate, migrate and produce large amounts of extracellular matrix proteins that can lead to the fibrosis seen in chronic pancreatitis. Pancreatic stellate cells are also responsible for the synthesis of various growth factors, cytokines, and chemokines, each playing a significant role in the complex network of paracrine and autocrine signaling pathways within the pancreatic tissue. + +These cells have been implicated in the progression of pancreatic cancer. Activated PSCs can stimulate the growth, invasion, and metastasis of pancreatic cancer cells. They also help form a dense, fibrous 'shield' around cancer cells, known as desmoplasia, which can make it more difficult for anticancer drugs to reach their target. Thus, a lot of research is being conducted on how to control or modify the behavior of pancreatic stellate cells to treat chronic pancreatitis and pancreatic cancer. " DOI:10.1007/s00424-017-1968-0|DOI:10.1136/gut.2008.170233|DOI:10.1038/labinvest.2012.161|DOI:10.1007/s00535-009-0013-2|DOI:10.1158/1078-0432.CCR-14-1051 +463 CL:0002503 CL_0002503 "Adventitial cells, also known as adventitial fibroblasts, are a cell type located in the outermost connective tissue layer of blood vessels, known as the adventitia. They are found throughout the body wherever blood vessels are present and constitute a significant part of the vessel wall structure. The adventitia is a loosely woven layer consisting of various cell types, collagen fibers, nerves and tiny blood vessels, and it is within this diverse environment that adventitial cells reside. + +Adventitial cells play a significant role in the maintenance and repair of blood vessels. When vessels endure mechanical stress or damage, these cells can differentiate and proliferate into myofibroblasts, contributing to vascular remodeling and tissue repair. They produce and release a variety of substances such as extracellular matrix components, including collagen, to provide structural support. Additionally, they have a strong influence on inflammation and immune responses within the vessel wall through their production of chemokines, cytokines, and adhesion molecules, thereby attracting leukocytes to the site of injury. Recent studies have demonstrated that adventitial cells may also play a role in disease progression, particularly in vascular diseases such as atherosclerosis and hypertension. In these settings, adventitial cells can proliferate excessively and contribute to vessel wall thickening, reduced flexibility, and narrowing of the lumen. " DOI:10.1146/annurev-physiol-030212-183802|DOI:10.1016/j.ajpath.2019.10.021|DOI:10.1155/2012/597439|DOI:10.1016/j.cardiores.2007.06.023|DOI:10.1161/CIRCRESAHA.111.263186 +464 CL:0002521 CL_0002521 "Subcutaneous fat cells, also known as adipocytes, reside under the skin, in the subcutaneous layer of our body. These cells primarily function as reserves for energy due to their ability to store lipids, particularly triglycerides, efficiently. Subcutaneous fat cells make up the most significant part of the adipose tissue, which provides insulation, cushioning, and serves as an energy reserve for individuals. The location of these cells varies with gender; typically, in males these cells are found in the area of the abdomen, whereas, in females, they are found in the thighs and the buttock region. + +These cells play an integral role in maintaining metabolic homeostasis. Beyond energy storage, subcutaneous fat cells are also engaged in numerous physiological processes such as maintaining body temperature, protecting the body from mechanical trauma, and functioning as an endocrine organ. They produce and secrete various bioactive molecules known as adipokines which have wide-ranging impacts on various bodily processes, including regulation of appetite, insulin sensitivity, inflammation, and immune function. + +Subcutaneous fat cells have a characteristic shape, being large, spherical, and filled with a large lipid droplet, unlike other cell types that contain smaller lipid droplets scattered throughout the cytoplasm. The diameter of these cells can range from 30 to over 300 micrometers, significantly larger than most other cells in the body. Of note, these cells also demonstrate a unique property called plasticity. They are able to change their volume dramatically, expanding to store more fat as it is taken up from the bloodstream, and shrinking when fats are released to provide energy. " DOI:10.1038/nature05483|DOI:10.1016/j.cell.2021.12.016|DOI:10.5114/aoms.2013.33181|DOI:10.1152/ajpregu.00257.2017|DOI:10.3389/fcvm.2020.00022 +465 CL:0002553 CL_0002553 "Fibroblasts of the lung, part of the connective tissue framework of the organ, are a specialized type of cells significant in maintaining the structure and function of respiratory tissues. They are spread throughout the interstitial spaces, providing structural support and elasticity to the lungs. Fibroblasts are essential for repairing and replacing damaged tissues, contributing to the lungs' resilience against mechanical stresses and injury. + +The primary function of lung fibroblasts is the synthesis and deposition of the lung extracellular matrix (ECM), a complex network of proteins and polysaccharides that form fibrous tissues. The ECM is crucial for the structural and biochemical properties of lung tissues, including their tensile strength, elasticity, and interface for cell-to-cell interactions. By producing key ECM proteins such as collagen, elastin, fibronectin, and proteoglycans, lung fibroblasts play a crucial role in maintaining the structural integrity and facilitating regular lung function. + +Furthermore, lung fibroblasts are involved in the lungs' wound healing and fibrotic processes. Upon injury, these cells can transition into an ""activated"" state, becoming myofibroblasts that produce significant amounts of collagen to form a scar tissue matrix for wound closure. However, overproduction of ECM by activated fibroblasts in chronic diseases can lead to fibrosis, a condition characterized by excessive lung tissue hardening and compromise of normal function. " DOI:10.1002/sctm.20-0526|DOI:10.1513/AnnalsATS.201406-240MG |DOI:10.1183/13993003.01805-2016|DOI:10.1513/pats.200708-146DR|DOI:10.1172/JCI93557 +466 CL:0002555 CL_0002555 "Fibroblasts of the mammary gland, often referred to as mammary fibroblasts, are a specialized type of cell located within the connective tissue of the mammary glands. These cells are integral to the structure and composition of the gland and are one of its primary cell types, specializing in the production of the extracellular matrix and collagen. They are involved in tissue remodeling, shaping the structure and maintaining the integrity of the mammary tissue by providing necessary rigidity and elasticity through their production of structural proteins. + +These cells also play a crucial role in mammary gland development and lactation. During mammary gland development, fibroblasts play a significant role in the induction of branching morphogenesis, which is vital for establishing proper ductal architecture. They also support the immune response within the mammary gland by producing and secreting cytokines and growth factors. + +Importantly, mammary fibroblasts are important in the context of breast cancer. Changes in the characteristics and behavior of these fibroblasts, often spurred by interactions with tumor cells, can promote cancer progression and metastasis. " DOI:10.1016/j.canlet.2012.06.014|DOI:10.3390/jcm11030799|DOI:10.1089/jir.2014.0026|DOI:10.1038/onc.2017.65|DOI:10.1016/j.bbadis.2012.10.013 +467 CL:0002548 CL_0002548 "Fibroblasts of cardiac tissue, or cardiac fibroblasts, are critical cells involved in the normal function and repair of the heart. They are essentially a type of non-muscle cell that are integral to the connective tissue and structural integrity of the heart. The primary role of cardiac fibroblasts is the synthesis and deposition of extracellular matrix (ECM) components. They synthesize a variety of ECM proteins, such as collagen, fibronectin, and elastin, forming a distinctive three-dimensional network that provides both mechanical and biochemical support for the cardiomyocytes. + +Cardiac fibroblasts also participate in crucial cellular communication within the myocardium - the muscular tissue of the heart responsible for pumping blood. They engage in intense cross-talk with cardiomyocytes and endothelial cells, influencing cell survival, growth, differentiation, and tissue repair processes. Particularly notable is their role in cardiac response to injury, such as myocardial infarction, where they proliferate intensely, and subsequently differentiate into myofibroblasts, contributing to scar formation and remodeling of cardiac tissue post-injury. + +Moreover, during pathological conditions of the heart, including cardiac fibrosis and heart failure, these fibroblasts can undergo phenotypic transformation into myofibroblasts, leading to an overproduction of ECM components and resulting in stiffening of the cardiac tissue. Over time, this diminishes the heart's ability to pump efficiently, sometimes leading to heart failure. Recent studies have also implicated abnormal behavior of cardiac fibroblasts in arrhythmogenesis. " DOI:10.1253/circj.CJ-16-1003|DOI:10.1161/CIRCRESAHA.109.209809|DOI:10.1186/1755-1536-5-15|DOI:10.1093/cvr/cvaa324|DOI:10.1126/science.adh9925 +468 CL:0002620 CL_0002620 "Skin fibroblasts specialized cells found in the dermis, the middle layer of the skin, where they play critical roles in maintaining skin health and functionality. Characterized by an elongated, spindle-like shape, skin fibroblasts are the principal active cells in the connective tissue of the skin. The primary function of skin fibroblasts is the maintenance and regeneration of the extracellular matrix, which provides structural and nutritional support for other skin cells, particularly keratinocytes and epithelial cells. These cells contribute to the production of collagen, elastin, and glycosaminoglycans - key proteins that maintain the elasticity, strength, and resilience of the skin. Through this function, skin fibroblasts help prevent skin aging and maintain tissue integrity, contributing to the skin's overall health and appearance. + +In addition, skin fibroblasts are implicated in the skin's wound healing process. Following injury, fibroblasts migrate to the wound site where they start proliferating and laying down new connective tissue. They play a vital role in the repair, regeneration, and healing of the skin; in the final stages of wound healing, skin fibroblasts help contract the healing tissue to minimize scar formation. Furthermore, recent research highlights their role in the immune response, with some studies indicating that skin fibroblasts can react to, and have a role in dealing with, pathogen invasion." DOI:10.3389/fimmu.2020.00648|DOI:10.1016/j.cell.2021.06.024|DOI:10.1016/j.stem.2022.07.006|DOI:10.2217/rme-2018-0073 +469 CL:0002617 CL_0002617 "Adipocytes of the breast, commonly known as breast fat cells, serve crucial structural, protective, and metabolic roles. These specialized cells, ubiquitously found within the breast's adipose tissue, primarily contribute to the organ's overall shape and cushioning, providing physical support to surrounding structures. + +Adipocytes are highly active metabolically and play a key role in lipid homeostasis, acting as principal sites for energy storage and release. These cells store excess energy in the form of triglycerides during times of energy surplus, releasing it during periods of energy deficit as free fatty acids and glycerol into the bloodstream. Therefore, regulation of breast adipocytes' size and number is critical to maintain overall energy balance. Moreover, during lactation, these fat cells assist in providing lipid molecules necessary for the production of breast milk. + +Moreover, breast adipocytes notably function in the endocrine system, secreting a wide array of hormones, growth factors, and cytokines, collectively referred to as adipokines. While adipokines have a wide range of effects, some are believed to exert crucial influence on breast cancer physiology. Indeed, excessive adipose tissue, leading to a state of chronic low-grade inflammation, is associated with an increased risk of several types of cancer, including breast cancer. " DOI:10.1007/s11154-021-09633-5|DOI:10.1016/j.phrs.2020.104741|DOI:10.1038/s41467-018-05911-0|DOI:10.3390/ijms21165760|DOI:10.1038/s41523-017-0015-9 +470 CL:1000299 CL_1000299 "The fibroblasts of connective tissue of the prostate are responsible for the production and maintenance of the extracellular matrix in the stromal region of the prostate gland. Fibroblasts, in general, are ubiquitous in the body's connective tissues, playing vital roles in wound healing and tissue repair. However, within the prostate, these cells exhibit unique characteristics targeted at the organ's health and function, permitting dynamic interactions with other cell types and fostering tissue architecture. + +Fibroblasts found in the prostate contribute significantly to the organ's function, particularly in maintaining tissue health and structure. These cells synthesize major structural proteins, such as collagen, elastin, and glycosaminoglycans—components of the extracellular matrix that provide structural support to the prostate tissue. This ensures the prostate's smooth muscle maintains its capability to contract and expand, thereby enabling proper function during urination and ejaculation. Furthermore, as the prostate gland undergoes adaptive alterations in response to ageing, fibroblasts play an integral role in coordinating these changes through their ability to modulate the extracellular matrix. + +Beyond maintaining tissue structure, the fibroblast of connective tissue of the prostate also participates actively in paracrine signaling—communication with other cell types within the prostate. Such cross-talk is especially significant in settings of inflammation, tissue injury, and in the pathogenesis of diseases such as benign prostatic hyperplasia and prostate cancer. In disease states, these fibroblasts can transition to a reactive phenotype characterized by increased proliferation and secretion of growth factors and pro-inflammatory cytokines. This transition excessively modulates the extracellular matrix, contributing to the diseased state. " DOI:10.1002/pros.23867|DOI:10.1101/cshperspect.a030510|DOI:10.1530/ERC-12-0085|DOI:10.1038/s41416-022-02085-x|DOI:10.3390/jcm7040068 +471 CL:1000304 CL_1000304 "Fibroblasts of connective tissue of nonglandular part of the prostate, also referred to as prostatic stromal fibroblasts, are specialized cells that are instrumental in maintaining the structure and function of the prostate. These cells constitute a crucial part of the non-glandular or stromal compartment of the prostate, which is composed largely of connective tissue and smooth muscle fibers. Being the most abundant cell type in the prostate stroma, fibroblasts are responsible for the production and maintenance of the extracellular matrix (ECM) via synthesis of collagen and elastin, structural proteins that provides crucial supportive and adhesive framework for the glandular elements of the prostate. These proteins provide tensile strength and elasticity, respectively, contributing to the healthy architecture of the prostate tissue. These cells also play a significant role in coordinating intercellular communication within the prostate by interacting with adjacent epithelial cells, endothelial cells, immune cells, and nerve cells, affecting cell growth, differentiation, and function. + +Prostatic stromal fibroblasts are actively involved in modulating local immune responses and tissue repair. Acting as local immunomodulatory cells, they can secrete a variety of cytokines and chemokines, influencing the functions of immune cells in the prostate microenvironment. Similarly, under pathological conditions, such as tissue injury or inflammation, these fibroblasts can transition into a more activated state, known as myofibroblasts, driving wound healing and tissue remodeling processes. It's worth noting that aberrant activation and proliferation of these fibroblasts can contribute to pathological situations, such as prostatic hyperplasia and prostate cancer, underscoring their importance in both health and disease." DOI:10.1038/s41416-022-02085-x|DOI:10.1101/cshperspect.a030510|DOI:10.3892/ijmm.18.5.941|DOI:10.1016/j.ajpath.2013.11.015|DOI:10.1210/me.2010-0340 +472 CL:1000305 CL_1000305 "Fibroblasts of the connective tissue of the glandular part of the prostate are fibroblasts found within the connective tissue encapsulating and supporting the glandular tissues in the prostate. These cells are responsible for producing and maintaining the extracellular matrix (ECM), a critical component of any connective tissue. The ECM provides a crucial scaffold or architecture for the tissue and plays a pivotal role in cell behavior and function. + +Fibroblast cells in the prostate, in particular, are involved in the regulation of the glandular activities, contributing to the homeostasis of this organ, primarily through their ability to secrete various growth factors, cytokines, and enzymes. They help regulate the growth and differentiation of prostatic epithelial cells, thus playing a role in maintaining proper glandular structure and function. Furthermore, these cells serve as a key conduit of intercellular communication due to their reciprocal interaction with the surrounding epithelial and stromal cells, influencing various aspects of cellular function such as proliferation, differentiation, and migration. + +Additionally, these cells have a significant part in pathological conditions that hit the prostate including prostate cancer and benign prostatic hyperplasia (BPH). In particular, when the prostate is afflicted by cancer, the fibroblasts are known to undergo a reactive change, transforming into myofibroblasts. These altered fibroblasts then exacerbate the disease by encouraging cancer cell growth and invasion, and promoting angiogenesis. Conversely, in BPH, the fibroblasts contribute to the excessive growth of prostatic tissue. " DOI:10.1016/j.diff.2011.05.007|DOI:10.3390/cancers12071887|DOI:10.1101/cshperspect.a030510|DOI:10.1016/j.ucl.2016.04.012 +473 CL:1000309 CL_1000309 "Epicardial adipocytes are a type of specialized cell found in the epicardial adipose tissue (EAT). This specific adipose tissue is located between the myocardium (the heart muscle) and the visceral pericardium (the innermost layer of the pericardium). Epicardial adipocytes store energy in the form of lipids; specifically, triglyceride droplets. These cells can rapidly mobilize and release these fatty acid molecules, when required, providing an effective and efficient energy source to the body. This energy is particularly important to the heart, which is one of the highest energy-demanding organs. The proximity of these specialized cells to the myocardium allows for direct and rapid transmission of these fatty acid molecules to meet the heart’s energy needs. + +Beyond their primary role in energy storage and regulation, epicardial adipocytes also play a pivotal role in providing a protective cushioning to the heart, releasing several beneficial adipokines which impacts cardiac function, along with acting as a source of stem cells. Adipocytes also contribute significantly to cardiac health and function in other ways. They have been found to secrete multiple bioactive molecules, known as adipokines, which can influence local cardiac function and overall cardiovascular health. Adipokines such as adiponectin, leptin and resistin regulate aspects of cardiac metabolism, inflammation, and contractility. Additionally, studies have also pointed towards epicardial adipocytes as a potential reservoir of adult epicardial progenitor cells, which can give rise to smooth muscle cells, endothelial cells and more adipocytes, thus contributing to cardiac repair and regeneration. Despite these important functions, an excess of epicardial adipose tissue has been associated with cardiovascular disease, indicating the importance of understanding and managing the balance of these unique cells in the body." DOI:10.1038/s41569-022-00679-9|DOI:10.3978/j.issn.2223-3652.2014.11.05|DOI:10.1016/j.tem.2011.07.003|DOI:10.3390/biology11030355|DOI:10.1038/ncpcardio0319 +474 CL:1000311 CL_1000311 "Adipocytes of the epicardial fat of the left ventricle are specialized cells localized within the epicardial adipose tissue, which is found enveloping the heart's outer layer, particularly the left ventricle. The primary function of these adipocytes is the storage and release of energy in the form of lipids, which facilitates efficient energy transfer to the myocardium when necessary. They are mesenchymal-derived cells filled with lipid droplets, giving them a unique and distinct appearance when compared to other cell types. + +The secondary, yet critically important function of these adipocytes revolves around their role as endocrine cells. They're involved in the production and secretion of various bioactive molecules, such as adiponectin, resistin, leptin, cytokines, and other adipocytokines, which play crucial roles in local and systemic metabolism, inflammatory responses, and myocardial protection. Furthermore, these adipocytes serve as a thermal insulation layer for the heart, protecting it from hypothermia and potentially mitigating the risk of arrhythmias caused by abrupt temperature changes. + +Dysregulation of the adipocytes of the epicardial fat of the left ventricle in their functions can lead to pathological conditions such as obesity, diabetes, and cardiovascular diseases like coronary artery disease and heart failure. For instance, it has been observed that increased volume of epicardial adipose tissue could be linked to the development of coronary atherosclerosis. " DOI:10.1038/ncpcardio0319|DOI:10.1038/s41598-023-41779-x|DOI:10.3390/ijms24076838|DOI:10.1093/eurheartj/ehab724.1266|DOI:10.1186/s12933-017-0528-4 +475 CL:1000692 CL_1000692 "The kidney interstitial fibroblasts are crucial cells found predominantly in the interstitium of the kidneys. These cells play a significant role in maintaining kidney structure and orchestrating key physiological procedures related to kidney function. The interstitium forms a complex network with other cells, capillaries, and the renal tubules, which are crucial for maintaining kidney functions. + +Functionally, these cells participate in renal homeostasis by synthesizing and secreting vital extracellular matrix (ECM) components, such as collagen, proteoglycan, and fibronectin, which contribute to the structural integrity of the kidneys. Additionally, these fibroblasts provide supportive tissues to nephrons (structural and functional units of kidneys), help in regulating fluid and electrolyte balance, along with providing an arena for immune response in case of any infection or damage. They are also integral to the regulation of kidney blood flow and maintenance of tubular structures by stabilizing capillaries through synthesis of angiogenic factors. + +Under pathological conditions, such as renal fibrosis, kidney interstitial fibroblasts can transform into myofibroblasts, which speed up the production and deposition of extracellular matrix proteins. This overproduction can lead to scar formation and affect the kidney's functionality, often leading to a chronic and progressive loss of renal function." DOI:10.1152/ajprenal.00284.2023|DOI:10.1111/j.1365-2613.2011.00764.x|DOI:10.1007/s00418-008-0452-5|DOI:10.3389/fphys.2016.00061|DOI:10.1038/s41598-019-38691-8 +476 CL:1001318 CL_1001318 "Renal interstitial pericytes are specialized mesenchymal cells that are located within the renal interstitium, forming an intricate network around the renal tubular and vascular structures. They are structurally and functionally interconnected with the other elements of the renal interstitial environment, contributing to overall tissue homeostasis. + +Functionally, renal interstitial pericytes act as crucial regulators of microvascular stability, providing physical support to the vasculature and maintaining the integrity of the blood-renal barrier. The pericytes' unique location, in close proximity to the endothelial cells, allows them to communicate and respond to cues from both the vascular and tubular compartments, assisting in the adjustment to physiological alterations. + +Additionally, renal interstitial pericytes have immunomodulatory properties, playing a key role in the local inflammatory response that follows renal injury. They influence immune cell recruitment and activation, and the production of growth factors, cytokines, and chemokines. In pathological conditions, such as the onset of kidney disease, these cells can transition to myofibroblasts, contributing to the pathogenesis of renal fibrosis." DOI:10.1038/s41581-018-0032-4|DOI:10.1093/ndt/gfs134|DOI:10.1111/acel.14075|DOI:10.1038/s41598-022-09331-5|DOI:10.2147/IJNRD.S37892 +477 CL:1001609 CL_1001609 "Muscle fibroblasts contribute indispensably to the maintenance, repair, and regeneration processes in the muscles tissue of the body. They are a subtype of fibroblasts, which are generally known as the 'builders' of the animal body's extracellular matrix (ECM) and are crucial players in wound healing. Occupying the connective tissues of muscles, muscle fibroblasts partake in the synthesis of the ECM components, including collagen, fibronectin, and laminin, that give the muscle its structure and flexibility. + +Interestingly, muscle fibroblasts metamorphose functionally during the process of muscle repair following injury. In this circumstance, they react to signals from injured muscle fibers and inflammatory cells, transforming into myofibroblasts. These newly-transformed myofibroblasts showcase contractile properties similar to smooth muscle cells and play a significant role in wound contraction during the healing process while continuing to produce ECM components to ensure reparative scaffolding. Furthermore, muscle fibroblasts secrete various growth factors, primarily those belonging to the 'Transforming Growth Factor-β' (TGF-β) family, to stimulate muscle repair and regulate immune responses. " DOI:10.1016/j.diff.2016.05.007|DOI:10.1002/cbin.10725|DOI:10.3389/fphys.2020.00253|DOI:10.3389/fimmu.2022.918223|DOI:10.1113/JP274403 +478 CL:4028006 CL_4028006 "The alveolar type 2 fibroblast cell, also known as AT2 cells, are specialized cells predominantly found in the alveolar lining of the lungs. Functionally, these cells play a dual role in maintaining lung homeostasis; they carry out the biomechanical regulation of the lungs and are active participants in the synthesis and secretion of surfactant, a substance essential for lung function. AT2 cells maintain elasticity and integrity of the lung tissue along with alveolar type 1 cells. Known for their distinctive cuboidal shape, they possess lamellar bodies in their cytoplasm which store and secrete pulmonary surfactant - a complex mixture of proteins and lipids. This surfactant reduces surface tension in alveoli and prevents their collapse, enabling efficient gas exchange process. + +Additionally, AT2 cells exhibit regenerative properties and serve as progenitor cells for the alveolar epithelium. In the event of lung injury, they proliferate and differentiate to restore the damaged epithelium, including the regeneration of type 1 cells. Recent research also indicates that AT2 cells are crucial in immune responses pertaining to the lung, contributing to defense against pathogens and mitigating inflammation. It's important to note that the dysfunction or abnormal conditions in AT2 cells are associated with several pulmonary diseases, including pulmonary fibrosis, acute lung injury, and lung cancer. " DOI:10.1165/rcmb.2016-0426PS|DOI:10.1038/s41420-019-0147-9|DOI:10.3390/ijms22052566|DOI:10.1038/s41556-021-00809-4|DOI:10.1038/s41598-018-30234-x +479 CL:4023054 CL_4023054 Mesothelial fibroblasts primarily originate from mesothelial cells, which form a protective layer known as mesothelium covering certain internal organs such as the heart, lungs, and abdominal cavity. Functionally, mesothelial fibroblasts excel in their capacity to synthesize and secrete extracellular matrix (ECM), a complex network of proteins that provides structural and biochemical support to surrounding cells. The ECM produced by mesothelial fibroblasts acts as a scaffold for tissue growth and remodeling, which is particularly important in wound healing and tissue repair processes. Additionally, these cells participate in immune response modulation within the mesothelium layer, interacting with various immune cells and mediating inflammatory processes. However, in certain diseases like fibrosis, these cells can excessively proliferate and produce ECM, leading to tissue thickening and organ malfunction. They also play a role in the progression of mesothelioma, a type of cancer that affects the mesothelium. DOI:10.1016/j.cell.2018.06.021|DOI:10.3747/pdi.2014.00188|DOI:10.3389/fphar.2015.00113|DOI:10.1016/j.ccell.2022.04.011|DOI:10.1038/s42003-018-0180-x +480 CL:0010006 CL_0010006 "Cardiac blood vessel endothelial cells are a specialized type of endothelial cells that constitute the innermost layer, or endothelium, of blood vessels within the heart, namely the arteries, veins and capillaries. They function as a semi-permeable barrier, regulating the exchange of nutrients, ions, and small molecules between the blood and surrounding cardiac tissues. Additionally, they control the trafficking of white blood cells into the myocardium, playing a vital role in immune surveillance and response to pathogens. + +An important feature of cardiac blood vessel endothelial cells is their contribution to vessel tone and blood pressure regulation. Endothelial cells release nitric oxide, a potent vasodilator, which helps to modulate blood vessel diameter as per the cardiac demands and maintain homeostasis. Moreover, these cells are active participants in the blood clotting process by expressing a variety of proteins and receptors that interact with platelets and plasma clotting factors. + +In pathological conditions, the function of cardiac blood vessel endothelial cells can change dramatically, leading to various cardiovascular diseases. In response to injury or disease, these cells can proliferate and migrate contributing to vessel repair or aberrant remodelling, promote inflammation, and contribute to the formation of atherosclerotic plaques. Their ability to switch from a quiescent, anticoagulant phenotype to a more active, procoagulant state is a principal factor in thrombosis. " DOI:10.1038/s41569-022-00770-1|DOI:10.1146/annurev.physiol.68.040104.124629|DOI:10.1161/ATVBAHA.117.310549|DOI:10.1161/circulationaha.105.602532|DOI:10.1016/j.ajpath.2020.10.001 +481 CL:0008019 CL_0008019 "Mesenchymal cells are a type of undifferentiated cell that possess the ability to develop into a wide variety of other cells. These cells originate from the mesoderm during embryonic development, which gives rise to tissues such as muscles, the skeletal system, and connective and vascular structures. Mesenchymal cells primarily function as progenitor cells with exceptional renewal capabilities and are characterized by their ability to migrate, aiding in tissue repair and regeneration. + +Mesenchymal cells play a critical role in the development and maintenance of various biological systems throughout the body due to their versatility and adaptability. They can differentiate into more specialized cells, including osteoblasts, adipocytes, and chondrocytes, which are essential for bone, fat, and cartilage tissues, respectively. Furthermore, they contribute to the vascular and lymphatic systems through the formation of pericytes and lymphatic endothelial cells, securing the integrity of the circulatory system. + +In the field of regenerative medicine, mesenchymal cells, particularly mesenchymal stem cells (MSCs), are of great interest due to their unique therapeutic potential. MSCs, for instance, have been implicated in wound healing and tissue repair because of their capacity to modulate the immune response. They can secrete a range of proteins and growth factors that aid in angiogenesis, the formation of new blood vessels, and the stimulation of resident progenitor cells to aid in tissue restoration. " DOI:10.1038/s41536-019-0083-6|DOI:10.21037/sci.2019.08.11|DOI:10.1016/S0076-6879(06)20016-8|DOI:10.1089/scd.2016.0109|DOI:10.1155/2016/1314709 +482 CL:0009099 CL_0009099 "Fibro/adipogenic progenitor (FAP) cells are a type of mesenchymal progenitor cell found commonly within skeletal muscle tissue. These versatile cells have a dual differentiation potential, which allows them to either mature into fibroblasts, which are responsible for connective tissue generation, or transform into adipocytes, which are fat-storing cells. FAP cells are instrumental in healthy tissue regeneration and remarkable for their flexibility, with their exact function varying based on the physiological state of the body and the surrounding microenvironment. + +In healthy tissue maintenance and regeneration, FAP cells respond to injury or damage by accelerating the healing process. Post-injury, FAP cells proliferate and facilitate the removal of necrotic debris, which in turn assists in the inflammatory response enabling the restoration of the tissue’s original architecture. Notably, FAP cells provide critical support to satellite cells, another cell type in the muscle tissue, which are primarily responsible for muscle growth and repair. The secretory profile of FAP cells, including growth factors like IL-6 and IGF-2, stimulates satellite cell proliferation and differentiation to restore muscle tissue. + +However, under pathological conditions, such as in muscular dystrophies or when subjected to chronic injury, the activity of FAP cells can be maladaptive. These altered conditions can lead FAP cells to differentiate into adipocytes rather than fibroblasts. This shift leads to fatty infiltration and fibrosis in the muscle tissue, exacerbating the disease and further diminishing muscle function. " DOI:10.1098/rsob.210110|DOI:10.3389/fphys.2019.01074|DOI:10.3390/cells8030232|DOI:10.1038/s41467-022-35524-7|DOI:10.1038/s41467-019-10438-z +483 CL:0008034 CL_0008034 "Mural cells are a type of cell found in the walls of blood vessels, particularly in capillaries and small arteries. There are two main types of mural cells: pericytes and vascular smooth muscle cells (VSMCs). These are specialized cells that have a crucial role in the maintenance of blood microvascular stability, and are heavily involved in angiogenesis, blood flow regulation, and vascular permeability. + +Pericytes ensure capillary stability by inhibiting endothelial cell proliferation, as well as controlling the diameter of blood vessels, interacting closely with endothelial cells to facilitate vascular contraction or dilatation, consequently regulating blood flow and pressure. Given their specialization, these cells are critical in maintaining the blood-brain barrier. + +Vascular smooth muscle cells are found in the walls of larger arteries and veins, as well as in some smaller vessels. These cells are also contractile and play a crucial role in regulating blood vessel tone and diameter. The contraction and relaxation of smooth muscle cells help control blood pressure and blood flow distribution. VSMCs are essential for the structural integrity of blood vessels and contribute to vascular remodeling in response to changes in blood flow or pressure. + +The interactions between endothelial cells and mural cells are critical for maintaining the proper functioning of the vascular system. Together, these cells form the vascular wall, and their coordinated activities are essential for various physiological processes, including blood circulation, tissue perfusion, and the response to injury or inflammation. Abnormalities in mural cell function can lead to a variety of diseases, including but not limited to diabetic retinopathy, Alzheimer's disease, and stroke. In tumor biology, these cells have been found to contribute to cancer growth and metastasis, highlighting their importance in maintaining vascular homeostasis. " DOI:10.1530/VB-22-0021|DOI:10.1215/S1152851705000232|DOI:10.3389/fcvm.2018.00078|DOI:10.3390/cells10030593|DOI:10.3389/fnins.2022.1010164 +484 CL:0009002 CL_0009002 "Inflammatory cells are a critical class of leukocyte (white blood cells) that play a pivotal role in the body's immune response against harmful substances, foreign material, infections, and injury. They originate from hematopoietic stem cells in the bone marrow, and upon maturation, they circulate in the bloodstream until they are activated and drawn towards sites of inflammation in the body, a process known as chemotaxis. These cells are vital participants in acute and chronic inflammation, crucial processes in the body's defense mechanism. + +The primary types of inflammatory cells include neutrophils, macrophages, eosinophils, basophils, dendritic cells, and lymphocytes, each specializing in a different aspect of the inflammatory response. For instance, neutrophils and macrophages are the first responders that primarily engulf and destroy pathogens. This is made possible through the process of phagocytosis, producing pro-inflammatory substances and communicating with other immune cells. Eosinophils and basophils are particularly effective against parasites and allergic reactions, releasing substances that combat these threats. Dendritic cells act as messengers between the innate and the adaptive immune system, capturing antigens and presenting them to T cells, a type of lymphocyte. Lymphocytes (T cells and B cells) carry out specific immune responses and produce antibodies, which neutralize pathogens. + +In one capacity or another, all inflammatory cells participate in the carefully orchestrated inflammation process. They can either promote inflammation, such as releasing inflammatory mediators or cytokines to recruit more immune cells to the site of inflammation or mitigate inflammation, aiding in the resolution of infection or injury. It is through this delicate balance between promotion and resolution that the inflammatory response can successfully protect the host from harm without causing excessive collateral damage. Dysregulation in this balance, such as an overactive or chronic inflammatory response, can result in various pathological conditions, including autoimmunity, allergies, and chronic inflammatory diseases. + +" DOI:10.18632/oncotarget.23208|DOI:10.1038/ni1275|DOI:10.1016/j.jaci.2009.12.980|DOI:10.1186/s13223-018-0278-1|DOI:10.1038/s41577-020-0391-5 +485 CL:0009005 CL_0009005 "Salivary gland cells are part of the complex cellular system that constitutes the salivary glands located in and around the oral cavity. These glands are responsible for the production and secretion of saliva, an essential component within the digestive process. Salivary gland cells can be broadly classified as acinar cells, which primarily produce the saliva, and ductal cells, which are involved in the modification and transportation of saliva. + +Acinar cells are the main secretory cells in the salivary glands and they exist in two types: serous or mucous. Serous acinar cells produce a watery, protein-rich saliva that contains digestive enzymes such as amylase, essential for the breakdown of starches. Mucous acinar cells produce a thicker, mucus-based saliva which helps lubricate the oral cavity and assists in the formation of the food bolus for easier swallowing - a critical part of digestion. The serous and mucous acinar cells exhibit specific morphology: Serous cells appear spherical or pyramidal with granule-rich cytoplasm, while mucous cells looks more tubular and have less granules, but more lipid droplets. + +Ductal cells present in salivary glands, also classified into either striated or intercalated cells, play a critical role in the modification and transportation of the saliva. The intercalated duct cells are nearest to the acinar cells and have a role in the initial modification of the ionic content of the saliva. Meanwhile, the striated duct cells, characterized by their infolded basolateral membranes, which give them a ‘striated’ appearance, are chiefly responsible for the resorption and secretion of electrolytes, leading to the further modification and conditioning of the saliva. This ductal modification process ensures that the saliva reaching the oral cavity performs optimal lubrication, digestion, and other protective functions." DOI:10.1038/s41536-020-00115-x|DOI:10.3390/cells8090976|DOI:10.1002/ar.23569|DOI:10.1067/mpr.2001.113778 +486 CL:0002584 CL_0002584 "Epithelial cells in the renal cortex play a crucial role in the structure and function of the kidneys. The renal cortex is the outer region of the kidney, and it contains various types of epithelial cells that are integral to the nephrons, the functional units of the kidney responsible for filtering blood and forming urine. Key epithelial cells located in this region include epithelial cells within the Bowman’s capsule, proximal convoluted tubule (PCT) cells, distal convoluted tubule (DCT) cells, and collecting duct cells. + +Bowmans’ capsule is located within the renal cortex and is composed of two layers of epithelial cells: the visceral layer which is made up of highly specialized cells known as podocytes that wrap around the capillaries of the glomerulus, playing a crucial role in forming the selective filtration barrier, and parietal layer, a single layer of simple squamous epithelium which is not involved in filtration. Together, these cells create the structural framework for the initial filtration of blood in the renal corpuscle, allowing the formation of the primary urine filtrate. This filtrate then proceeds through the renal tubules for further processing and modification before becoming urine. + +PCT cells are part of the nephron and play a significant role in reabsorbing water, ions, and nutrients from the filtrate back into the bloodstream. DCT cells are important for further ion regulation and excretion of waste, thereby contributing to the final adjustments in electrolyte balance and acid-base regulation. Collecting duct cells are found in both the renal cortex and the renal medulla. Collecting ducts receive urine from multiple nephrons and play a role in the final concentration or dilution of urine. Principal cells and intercalated cells within the collecting ducts are types of epithelial cells that contribute to water and electrolyte balance. Principal cells play a role in water and sodium reabsorption and potassium secretion, contributing to the concentration and composition of urine whereas intercalated cells are involved in maintaining acid-base balance by secreting hydrogen ions or bicarbonate ions. + +Thus, epithelial cells in the renal cortex collectively contribute to the filtration, reabsorption, and secretion processes that occur within the nephrons, helping regulate the body's water and electrolyte balance, blood pressure, and the excretion of waste products." DOI:10.1146/annurev-physiol-052521-121841|DOI:10.1016/j.semnephrol.2012.06.007|DOI:10.1007/s42452-019-1840-2|DOI:10.1681/ASN.2019040415|DOI:10.2215/CJN.08880914 +487 CL:0002681 CL_0002681 "Kidney cortical cells are cells located within the renal cortex, the outer part of the kidney which contains the renal corpuscles and the renal tubules excluding the nephron loop. The kidney is essentially divided into two major sections, namely, the outer cortex and the inner medulla, with the cortical cells crucially constituting the cortex. + +Kidney cortical cells' primary function is significant for the renal system's physiological balance. These cells play a pivotal role in contributing to primary renal functions such as the filtration of blood, reabsorption of water and crucial electrolytes, and secretion of wastes. Essentially, the processes of blood filtration, solute reabsorption, and waste excretion, which ensure our blood remains clean and chemically balanced, are all carried out in the microscopic units comprised predominantly of cortical cells. + +The kidney cortical cells are unique due to their structural and functional adaptation to aid in both passive and active transportation of molecules. Their contribution to the kidneys' essential function necessitates resilience to toxic substances, adaptive reabsorption mechanisms, and efficient waste secretion. Any damage or disease that impinges on these cells, such as Chronic Kidney Disease (CKD), can seriously hamper the renal process, consequently affecting overall bodily functions. " DOI:10.1146/annurev-physiol-052521-121841|DOI:10.1001/jama.2019.14745|DOI:10.1002/cphy.c110061|DOI:10.1016/S0140-6736(21)00519-5 +488 CL:1000452 CL_1000452 "Parietal epithelial cells (PECs) are key constituents of the renal glomerulus, a microscopic structure in the kidney where blood is filtered to produce urine. These cells form a flat, mono-layered cellular structure that lines the Bowman's capsule, an integral part of the nephron - the functional unit of a kidney. They facilitate the initial step of nephron filtration by forming the outer wall of the renal corpuscle and enveloping the capillaries of the kidney's glomerulus. Additionally, these cells connect to the basal lamina, a layer of extracellular matrix secreted by epithelial cells, which serves as a filter for diffusion of soluble molecules. + +Functionally, parietal epithelial cells are vital for maintaining the structural integrity of the glomerulus. They form a barrier that helps control the movement of particles from the bloodstream to the Bowman's space, the initial site where filtered fluid is collected before being converted to urine. Between PECs, there are filtration slits that allow the passage of water, ions, and small molecules, while restricting larger components like blood cells and proteins, thus aiding in selective filtration. Moreover, PECs have a reparative role in glomerular diseases, increasing in numbers and changing their cellular characteristics to replenish podocytes, the cells lining the blood capillaries that may get lost or damaged due to various renal pathologies. + +Scientific research indicates that PEC activation and proliferation can be a double-edged sword. On one hand, it serves as a crucial adaptive response during physiological stress or damage, recognizing injury, proliferating, and differentiating to repair the glomerular structure. On the other hand, excessive PEC proliferation and migration may lead to pathological changes like the formation of crescents (crescentic glomerulonephritis) or segmental scars (focal segmental glomerulosclerosis), contributing to progressive kidney disease. Overall, parietal epithelial cells are indispensable to renal filtration and repair and are progressively being acknowledged as potential therapeutic targets for glomerular diseases." DOI:10.1038/nrneph.2014.1|DOI:10.1007/s00441-017-2600-5|DOI:10.1681/ASN.2008070795|DOI:10.1007/s00441-021-03513-9|DOI:10.1681/ASN.2010090970 +489 CL:1000505 CL_1000505 "Cells of the renal pelvis are critical components of the urinary system due to their specialized role in urine transport and management. The renal pelvis is the funnel-shaped structure that collects urine filtered by the kidney and through peristalsis, a systematic contraction and relaxation mechanism, propels it towards the ureter, which is the tube leading down to the urinary bladder. These cells bear primary responsibility of facilitating smooth urine flow through this system, thus playing an instrumental role in the excretion and regulation of waste products from the bloodstream. + +One of the vital functions of the kidney pelvis cell pertains to barrier protection. The cells of the renal pelvis are part of the urothelium - a type of transitional epithelium that lines much of the urinary system, with traits of durability and stretchiness to accommodate periodic fluctuations in urine volume. These cells have an incredible surface flexibility and the ability to form a tight, impermeable barrier, which prevents toxic substances circulating within the urine from seeping back into the bloodstream. " DOI:10.1172/JCI21402|DOI:10.1038/ki.1987.43|DOI:10.1152/nips.1416.2002|DOI:10.1152/ajplegacy.1974.226.6.1413|DOI:10.1111/j.1748-1716.2011.02261.x +490 CL:1000497 CL_1000497 "Kidney cells, also known as renal cells, are a diverse set of biological units that comprise the organ primarily responsible for detoxification, blood filtration, and homeostasis of electrolyte balance in the body. There are several specialized types of kidney cells, including but not limited to, nephrons, podocytes, and collecting duct cells, each with its designed role and function in the renal system. They work collectively and distinctively to maintain optimal renal function and contribute intricately to both the microscopic and macroscopic structure of the kidney. + +Nephrons, the fundamental functional units of kidneys, consist of a myriad of cell types such as proximal tubule cells, distal tubule cells, loop of Henle cells, each type specialized for a specific part of the filtration process. For example, glomerular endothelial cells in the nephron filter the blood, reabsorbing necessary substances like glucose and amino acids and rejecting unwanted waste, which forms urine. The uniquely-shaped podocytes, with their foot-like extensions, envelope the glomerular capillaries playing a critical role in the blood filtration barrier preventing the leakage of plasma proteins into the urine. + +Collecting duct cells are another integral part of kidney cells that function in the fine-tuning of the concentration of urine and maintaining the body's water balance. These cells respond to anti-diuretic hormone (ADH) and adjust the water reabsorption accordingly, preventing dehydration or water intoxication depending on the body's needs. Besides these, the renal interstitial cells support the structure of the kidney and provide a medium between the nephrons and the blood vessels. +" DOI:10.1146/annurev-physiol-052521-121841|DOI:10.1038/s41536-021-00156-w|DOI:10.1038/s41597-019-0351-8|DOI:10.1186/s13287-021-02266-0 +491 CL:1000507 CL_1000507 "Kidney tubule cells form the crucial functional units of the kidneys, known as nephrons. These cells are primarily involved in the filtration, reabsorption, and secretion processes that help the kidneys maintain the body's fluid, electrolyte balance, and pH homeostasis. Kidney tubule cells are specialized epithelial cells, and the renal tubule is divided into specific segments. These segments include the proximal tubule, the loop of Henle, the distal tubule, and the collecting duct. Each segment's cells have a specific role; for example, cells in the proximal tubule function in the reabsorption of solutes and water, while those in the distal tubule and collecting duct regulate the body's acid-base balance. + +Among their many functions, kidney tubule cells reabsorb essential substances such as glucose, water, and electrolytes like sodium, potassium, and bicarbonate from the glomerular filtrate back into the bloodstream. They also excrete waste products like urea and creatinine from the blood into the filtrate for eventual elimination from the body. Given their functions, pathological chances in these cells can lead to kidney disease." DOI:10.1146/annurev-physiol-052521-121841|DOI:10.1002/cphy.c110061|DOI:10.2215/CJN.04480413|DOI:10.2215/CJN.05920613|DOI:10.1007/978-3-319-51436-9_7 +492 CL:0000001 CL_0000001 "Primary cultured cells are cells directly extracted from living organisms and then cultivated in a laboratory under controlled environmental conditions. After extraction, these cells can grow and reproduce when provided with the appropriate nutrients. The establishment of primary cell cultures involves processes like tissue dissection, enzymatic or mechanical disaggregation, suspension, and plating. These cells closely mimic the biochemical and physiological conditions of cells in vivo, providing a more realistic model of biological function compared to other cell culture systems. + +Retaining most physiological and morphological characteristics of the original tissue, primary cultured cells are a powerful tool for modeling diseases, drug responses, and basic biological functions such as synthesis and metabolism. They find extensive use in research fields such as cellular biology, genetics, pharmacology, oncology, and toxicology. + +Despite their genetic stability, primary cultured cells have a finite lifespan and are not immortal. They undergo senescence after a specific number of population doublings, influenced by genetic, environmental, and epigenetic factors. Given their limited lifespan, primary cells are crucial for experimental replicability, and their cultivation demands meticulous care to prevent changes that might alter cell identity or function." https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/primary-cell-culture|DOI:10.1007/978-0-387-89626-7_18|DOI:10.1007/978-0-387-89626-7_18 +493 CL:0000003 CL_0000003 "A native cell, in its natural and unaltered state within an organism, operates according to its genetic programming and interacts with the organism's biological system. This term distinguishes cells that have not undergone genetic or mechanical modifications for research or therapeutic purposes. + +Native cells play a crucial role in maintaining homeostasis, contributing to the overall balance necessary for proper bodily function. Specialized functions of various cell types, such as neurons facilitating neurotransmission and epidermal skin cells protecting against external elements, collectively support this delicate equilibrium. Red and white blood cells perform vital roles in oxygen transport and immune response, respectively. + +Communication among native cells is essential for multicellular organisms. Cells send and receive signaling molecules to coordinate activities and respond to environmental changes or threats. This communication is particularly crucial in processes like wound healing, immune responses, and complex events such as embryonic development. Essentially, the unaltered functions of native cells are indispensable for sustaining health and functionality in living organisms." https://www.ncbi.nlm.nih.gov/books/NBK279255/|https://www.ncbi.nlm.nih.gov/books/NBK2263/ +494 CL:0000000 CL_0000000 "A cell, often referred to as the ""building block of life,"" serves as the fundamental unit of structure and function in all living organisms. Functioning as the smallest entity capable of life processes, cells likely originated around 3.8 billion years ago, evolving into the diverse cell types seen in various life forms today. + +Cells fulfill a spectrum of organism-specific functions, including structural support, nutrient utilization, energy conversion, metabolic initiation, information transmission, and reproduction. Despite their specialization, all cells share common characteristics. Each cell is encased in a membrane, separating it from its environment, and contains organelles with specialized functions. These organelles, such as the nucleus for DNA housing, mitochondria for energy production, endoplasmic reticulum for synthesis, and lysosomes for waste processing, contribute to the remarkable diversity of life processes observed in different organisms. + + + + + +" DOI:10.33974/ijrpps.v1i1.108|https://www.ncbi.nlm.nih.gov/books/NBK9841/|https://www.ncbi.nlm.nih.gov/books/NBK9903/ +495 CL:0000064 CL_0000064 "A ciliated cell is a distinct type of eukaryotic cell and feature specialized hair-like structures called cilia on their surface. Found in various tissues like the respiratory tract, reproductive system, and nervous system, these cells play crucial roles facilitated by ciliary movement, driven by external fluid or programmed cell control. + +The primary function of ciliated cells is to move particles or fluid over the cell surface. In the respiratory tract, they propel mucus and particles out of the lungs, aiding in airway clearance and preventing the entry of harmful substances. In the female reproductive system, ciliated cells guide the ovum from the ovaries to the uterus for fertilization. + +In the central nervous system, specifically the brain's ventricular system, ciliated ependymal cells promote cerebrospinal fluid (CSF) flow. Their coordinated ciliary movement is vital for maintaining CSF circulation, contributing to brain function and homeostasis. Thus, mutations or malfunctions of ciliated cells can lead to respiratory disorders, infertility, and hydrocephalus." DOI:10.1002/mrd.23650|DOI:10.1146/annurev-physiol-021014-071931|DOI:10.3389/fnmol.2022.927479 +496 CL:0000233 CL_0000233 "Platelets, also known as thrombocytes, are small, disc-shaped cell fragments devoid of a nucleus, yet remarkably intricate and multi-functional. They originate from the megakaryocytes in the bone marrow via a process called thrombopoiesis. Platelets are central to hemostasis, a process that prevents bleeding from broken or damaged blood vessels and facilitates wound healing. In their resting state, platelets are inactive but become quickly activated when an injury occurs. + +Platelets function in the initiation and regulation of coagulation or clotting, which is a complex process involving several bioactive molecules. When a blood vessel is injured, the inner lining of the vessel, the endothelium, gets disrupted, exposing the underlying tissue matrix. This leads to platelet activation and adhesion to the injury site, initiating the clotting cascade. Platelets release granules packed with clotting factors, proteins, enzymes, and more platelets, which further propagates the clotting process. When activated, platelets also change their shape from discoid to a spherical form with protruding pseudopods that enables them to adhere more readily to the site of injury and mesh with one another to form a 'platelet plug'. + +Additionally, platelets serve other physiological roles. They release growth factors enhancing tissue regeneration and wound healing. They also play a significant role in inflammation, innate immunity, and antimicrobial host defense, as they interact with leukocytes and may sequester microbes. Platelets are involved in maintaining the integrity of the blood vessels and angiogenesis, the formation of new blood vessels. Proper functioning of platelets is critical for maintaining homeostasis, while dysregulation can lead to conditions such as thrombosis or bleeding disorders. +" DOI:10.1038/s41569-018-0110-0|DOI:10.3389/fimmu.2019.01731|DOI:10.1007/s10555-017-9677-x|DOI:10.1016/j.blre.2014.10.003 +497 CL:0000559 CL_0000559 "Promonocytes are precursor cells in the mononuclear phagocyte system, which includes the progenitors in the bone marrow, circulating monocytes and macrophages in various tissues. During monocytopoiesis, promonocytes form after monoblasts differentiate, and precede the development of monocytes and macrophages, which play an integral role in the immune system. + +Promonocytes are large, often round cells with a high nucleus to cytoplasm ratio. Their cytoplasm is laden with small azurophilic granules, and they are similar in appearance to myelocytes and metamyelocytes. + +The maturation into monocytes is the key function of promonocytes. Once matured, they navigate their way to the bloodstream and their primary role comes into effect. Monocytes circulate in the blood for a few days before migrating to tissues to become either macrophages or dendritic cells. These cells then proceed to ingest pathogens like bacteria and viruses, helping to keep the body healthy. Thus, promonocytes play a central role in the immune system by paving the way for the development of cells that fight off toxins and attacks. + +Beyond their immune response role through differentiation, promonocytes may participate in processes such as wound healing and inflammation regulation. Defects or disruptions in promonocyte function have been linked to health disorders, including monocytic-lineage leukemias such as chronic myelomonocytic leukemia (CMML), although it is worth noting that morphologic distinction between promonocytes and other monocytic cells of various differentiation levels is difficult. +" DOI:10.1016/B978-0-323-35762-3.00027-5|DOI:10.1111/ijlh.13212|https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/promonocyte|DOI:10.1182/blood.2022015850 +498 CL:0000556 CL_0000556 "A megakaryocyte is a large, unique, and complex cell type found primarily in the bone marrow, the spongy, semi-solid tissue located in the medullary cavities of certain bones. The term ‘megakaryocyte’ is derived from the Greek 'mega', meaning great, and 'karyon', referring to the nucleus. Megakaryocytes are characterized by their large size, typically with a diameter of 50-100 µm in humans, and the presence of a multilobulated nucleus; they are the largest hematopoietic cells in the bone marrow but also the rarest cells. + +The primary function of a megakaryocyte is the production of platelets, also known as thrombocytes. Platelets are small, anucleate cell fragments that play a crucial role in the process of hemostasis, the arrest of blood loss from a damaged blood vessel. The process begins when the megakaryocyte extends long, branching processes called proplatelets, into the sinusoidal blood vessels present in the bone marrow. These proplatelets then fragment into the discoid structures recognized as platelets. Each megakaryocyte can produce thousands of platelets during its lifespan. + +Apart from platelet production, megakaryocytes are involved in several other functions. They express immune-sensing receptors such as Fc-γ receptor and Toll-like receptors and produce factors such as platelet factor 4 and platelet-derived growth factor that can stimulate the immune system. Also, in certain pathological conditions, megakaryocytes release TGF-β and PDGF and contribute to bone marrow fibrosis, a condition characterized by excessive accumulation of fibrous tissue in the bone marrow leading to anemia. Recent studies have also highlighted the role of megakaryocytes in regulating hematopoiesis, the process of blood cell production. They can influence the bone marrow microenvironment and control the behavior of hematopoietic stem cells, the progenitors of all types of blood cells. +" DOI:10.1002/JLB.MR0718-261RR|DOI:10.1161/ATVBAHA.119.312129|DOI:10.1083/jcb.201304054|https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/megakaryocyte|DOI:10.1186/s12967-023-04393-z +499 CL:0000763 CL_0000763 "Myeloid cells represent a diverse group of immune cells that originate from hematopoietic stem cells in the bone marrow and differentiate along the myeloid lineage. This group comprises various cell types with different functions, including polymorphonuclear granulocytes (neutrophils, eosinophils, and basophils), and mononuclear phagocytes (monocytes, macrophages, dendritic cells), as well as megakaryocytes/platelets. Together, the various myeloid cells play crucial roles in protecting the organism against pathogens, stimulating adaptive immunity, remodeling tissue after injury or severe infection, and maintaining homeostasis, including suppression of immune responses in the lungs and placenta to limit potential damage. + +Granulocytes, monocytes, and macrophages form the body's first line of defense against invading pathogens. They carry out this function through several mechanisms, including phagocytosis, where they engulf and destroy foreign bodies, as well as the release of antimicrobial substances. Neutrophils, for example, are the most abundant white blood cells and are rapid responders to infection. They exhibit strong phagocytic activity against bacteria and fungi. + +Monocytes circulate in the bloodstream and migrate into tissues, transforming into macrophages or dendritic cells in response to infections, where they further contribute to immune reactions. Dendritic cells serve as antigen-presenting cells, engulfing invaders, processing their antigens, and presenting them to T cells, thereby stimulating an adaptive immune response. Eosinophils and basophils, while less abundant, play instrumental roles in defense against parasitic infections and participate in allergic responses. Finally, under the myeloid lineage, megakaryocytes are responsible for platelet production, which is crucial for blood clotting and wound healing. + +A specific group of so-called myeloid-derived suppressor cells (MDSCs) are pathologically activated neutrophils and monocytes that are thought to play an important role in the pathogenesis of different inflammatory conditions, including different types of cancer and chronic infections. +" DOI:10.1038/s41577-019-0141-8|DOI:10.1146/annurev-immunol-081022-113627|https://www.sciencedirect.com/topics/medicine-and-dentistry/myeloid-cell|DOI:10.1016/j.semcdb.2016.08.006|DOI:10.1038/s41577-020-00490-y +500 CL:1001107 CL_1001107 "The Kidney Loop of Henle Thin Ascending Limb Epithelial Cells are a highly specialized cell type that resides in the thin ascending limb of the Loop of Henle of the nephrons of the kidneys. The nephron is the functional unit of the kidney involved in the purification of blood and the production of urine, and the Loop of Henle serves a critical role in this process. + +The primary function of the these cells is the selective reabsorption of electrolytes and the regulation of urine concentration. Specifically, these cells are significantly permeable to solutes such as sodium and chloride ions but impermeable to water. This selective reabsorption of electrolytes contributes to the generation of a concentrated medullary interstitium. The absorption of ions without the concurrent absorption of water leads to an increasing osmolarity of the fluid from the thin ascending limb towards the thick ascending limb of the nephron. This process is critically essential for the kidneys' ability to produce concentrated urine. + +These cells contribute to the counter-current multiplier system, a mechanism that allows the kidney to produce urine that is hypertonic to plasma, thereby varying the volume and concentration of the urine. By creating a steep osmotic gradient in the interstitial fluid that surrounds the Loop of Henle, the thin ascending limb epithelial cells allow for the passive reabsorption of water in the subsequent collecting duct. This mechanism is essential in maintaining body water homeostasis, especially under conditions of dehydration." DOI:10.1002/cphy.c110019|DOI:10.1016/B978-0-323-05876-6.00001-0|DOI:10.1152/ajplegacy.1967.212.2.357|https://www.kidney-international.org/article/S0085-2538(15)33907-7/pdf +501 CL:1001108 CL_1001108 "The kidney loop of Henle medullary thick ascending limb epithelial cell, often simply referred to as the thick ascending limb (TAL) cell, is a specialized cell found within the nephron of the kidney. This specific part of the nephron, known as the Loop of Henle, is responsible for concentrating urine by actively reabsorbing ions and indirectly reabsorbing water to create a concentrated medullary interstitium. The TAL cell plays a critical role in this task, lining the inner tube of the ascending limb and facilitating the movement of various ions against their concentration gradient. + +TAL cells are architecturally organized with the apical side facing the tubular lumen and the basolateral side interfacing with the interstitial fluid. They possess several unique characteristics that distinguish them from other nephron segment cells, one of which is an abundance of mitochondria, required to provide the energy needed for active transports. These cells are equipped with various ion transporters, channels, and pumps that drive the reabsorption process. + +TAL cells also participate actively in various physiological processes. Their activity aids in controlling the body's water homeostasis, electrolyte balance, blood pressure, and even blood pH. Moreover, they respond dynamically to the body's changing needs, modulating their activity under hormonal influences." DOI:10.2215/CJN.04480413|DOI:10.2147/IJNRD.S154000|DOI:10.1152/ajprenal.00261.2019|DOI:10.1161/HYPERTENSIONAHA.108.120246|DOI:10.1152/ajprenal.00261.2019 +502 CL:1001109 CL_1001109 "The kidney Loop of Henle cortical thick ascending limb epithelial cell (often abbreviated as TAL cell), contributes significantly towards the kidney's fundamental role in maintaining homeostasis, frequently pertaining to volume status and electrolyte balance in the body. This cell type is an integral part of the nephron, the central, functional unit of the kidney. Specifically, these cells line the thick ascending limb (TAL) in the Loop of Henle, a section crucial for the reabsorption of electrolytes in the nephron and part of the multi-step process of urine formation. + +The TAL cells play a fundamental role in the reabsorption of sodium, chloride, and potassium from the filtrate that passes through the Loop of Henle. It utilizes a Na-K-2Cl symporter, a type of cotransporter, on its apical (urine-facing) surface. This protein facilitates the uptake of these ions from the filtrate against their concentration gradient, into the cell interior. Moreover, the basolateral side, which comes in contact with the interstitial fluid, contains a Na+/K+ ATPase, thereby actively transporting sodium out of the cell to maintain the concentration gradient and facilitating the renal countercurrent mechanism. Additionally, these cells are impermeable to water, hence, the reabsorption of electrolytes without an accompanying water reabsorption contributes to the hyperosmotic medullary interstitium, a unique environment in the kidneys that assist in the production of concentrated urine. " DOI:10.1152/ajprenal.00261.2019|DOI:10.1152/ajprenal.00261.2019|DOI:10.1007/s00424-008-0607-1|DOI:10.1152/physrev.2001.81.1.345 +503 CL:1001111 CL_1001111 "The ""Kidney Loop of Henle Thin Descending Limb Epithelial Cell” also known as the thin descending limb (tDL) cell, is a component of the nephron, which is the functional unit of the kidney responsible for filtration, reabsorption, and secretion to form urine. These cells are located within the Loop of Henle, a U-shaped structure that extends from the proximal tubule and contributes to the mechanism of urine formation. The tDL is distinguished by its simple squamous epithelium and its primary function is to regulate water reabsorption, contributing significantly to the body's fluid balance management. + +Functionally, the thin descending limb epithelial cells are characterized by their high permeability to water, and comparatively low permeability to salts and urea. This unique feature allows for water reabsorption from the luminal fluid into the interstitium, driven by the osmotic gradient established by the ascending limb of the Loop of Henle and the collecting ducts. This effectively concentrates the urine, preserving water within the body. Furthermore, these cells play an integral role in the countercurrent multiplier mechanism, a system that achieves concentration of urine in the kidney's medullary interstitium. " DOI:10.1152/ajprenal.00404.2011|DOI:10.1073/pnas.85.8.2873|DOI:10.1002/cphy.c110019|DOI:10.1038/ki.1990.260 +504 CL:0000861 CL_0000861 "The elicited macrophage, also commonly referred to as an activated macrophage, is a specialized type of cell that forms a critical part of the immune response. These cells originate from monocytes, a type of white blood cell that circulates in the bloodstream. In response to infection, inflammation, or tissue injury, monocytes leave the bloodstream, enters the inflamed tissue, and differentiates into a macrophage. The term ""elicited"" indicates that these cells have been activated or stimulated, usually through exposure to mediators such as lipopolysaccharide (LPS) or interferon-gamma (IFN-gamma), and have acquired enhanced microbicidal and tumoricidal capabilities. + +One of the hallmark features of elicited macrophages is their remarkable plasticity, which enables them to assume distinct activation states depending on the signals they receive. Macrophage activation states span a spectrum of phenotypes and functions, but are often classified into a few groups for simplicity. Classically activated macrophages, also known as M1 macrophages, are typically induced by pro-inflammatory cytokines such as interferon-gamma (IFN-γ) and microbial products like lipopolysaccharide (LPS). These M1 macrophages exhibit potent microbicidal and pro-inflammatory functions, aiding in the clearance of pathogens and the initiation of immune responses. Alternatively activated macrophages, or M2 macrophages, are typically associated with tissue repair, wound healing, and immunoregulation. They are induced by anti-inflammatory cytokines such as interleukin-4 (IL-4) and interleukin-13 (IL-13), as well as factors released during tissue remodeling. Elicited macrophages can transition between phenotypes in response to changing environmental cues, thereby exerting context-dependent effects on immune and tissue homeostasis. + +Elicited macrophages perform a range of functions in order to respond to the type of insult that has occurred. They can phagocytose cellular debris, foreign substances, microbes, and cancer cells. They can also act as antigen-presenting cells (APCs). After ingesting a pathogen, these cells present fragments of the pathogen on their surface using a molecule class called Major Histocompatibility Complex (MHC) II cluster. These antigens then interact with the cognate T cell receptors on T-cells, triggering a larger immune response. Elicited macrophages can produce numerous substances that are essential to the immune response. This includes pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukins, chemokines, and reactive oxygen and nitrogen species that help neutralize pathogens. Additionally, they can play a role in wound healing, growth and tissue reconstruction by secreting factors that promote angiogenesis. While the activation of elicited macrophages is essential for the immune response, prolonged or inappropriate activation can contribute to a range of pathological conditions, including chronic inflammation, autoimmunity, and cancer." DOI:10.3389/fimmu.2020.00269|DOI:10.1016/j.chembiol.2020.12.005|DOI:10.1038/s41586-023-06002-x|DOI:10.1038/nri2448|DOI:10.3389/fimmu.2021.708186 +505 CL:0000545 CL_0000545 "T-helper 1 (Th1) cells are a subset of mature T lymphocytes. These cells are integral parts of the adaptive immune system, and their primary function is in cell-mediated immunity. Th1 cells play a pivotal role in the immune response against intracellular pathogens. Activation of naive T lymphocytes produces different effector cell phenotypes based upon the cytokine signals they receive during activation. Th1 differentiation is favored by interleukin-12 (IL-12), IL-18, type 1 interferons, and interferon-gamma (IFN-γ). + +Th1 cells exert their immune function by producing and releasing certain types of cytokines such as IFN-γ and IL-2. IFN-γ activates macrophages and enhances their ability to destroy intracellular pathogens, including viruses and certain bacteria. These cytokines also play a role in activating macrophages, natural killer (NK) cells, CD8+ T cells, and B cells, thus perpetuating the immune response. Release of cytokines by Th1 cells at the site of infection, dependent on the cell’s recognition of the antigen via MHC-II molecules, helps to direct the immune response. + +Some Th1 effector cells appear to develop into memory T cells. This enables them to react more swiftly and robustly if the same pathogen is encountered again. These cells Th1 cells are also involved in the pathogenesis of several types of autoimmune diseases, such as multiple sclerosis and type 1 diabetes. " DOI:10.1016/B978-0-12-374279-7.08002-4|DOI:10.1016/B978-0-7020-6896-6.00016-8|DOI:10.1146/annurev-immunol-103019-085803|DOI:10.1016/j.jaci.2014.11.001 +506 CL:0000785 CL_0000785 "A mature B cell is a critical component of the body's immune system, with different mature B cell subsets providing distinct functions in both adaptive and innate humoral immune responses. The primary role of these cells in the immune function is to produce antibodies or immunoglobulins which serve to neutralize or aid in the destruction of pathogens – microbes, viruses or any toxin that is harmful to the body. + +Mature B cells develop from immature B cells that have migrated from the bone marrow to the spleen where they differentiate through transitional B cell stages (called T1 and T2). Following antigen activation, mature B cells then undergo further developmental stages. + +Before encountering a specific antigen, mature B cells are called ‘naïve’ B cells. Due to the high variability of B cell receptors (BCR) even within the same individual, each naive B cell is capable of recognizing a unique molecular structure, leading to an immensely diverse repertoire of these cells ready to react against a wide array of pathogenic threats. + +Mature B cell subsets include follicular and marginal zone B cells, so named because they are enriched in the follicles and marginal zones of the spleen, respectively, although they are not confined to these compartments. Follicular B cells depend upon T cells for activation against specific antigens, and this reaction forms germinal centers in which the follicular B cells differentiate into germinal center B cells. Following class switch recombination and somatic hypermutation, these cells can differentiate into plasma cells, which secrete high-affinity antibodies, or memory B cells, which contribute to immunological memory when re-challenged by the same antigen. Marginal zone B cells can function as antigen-presenting cells and can also rapidly respond to blood-borne antigens by differentiating into antibody-secreting plasma cells with short half-lives. + +In addition to follicular and marginal zone B cells, there is a third population of mature B cells, known as B1 cells, which have have a distinct haematopoietic origin in the fetal liver and are located in a number of tissues including the spleen, intestine, and the pleural and peritoneal cavities. +" DOI:10.1016/B978-0-12-397933-9.00007-2|DOI:10.1007/978-981-15-3532-1_1|DOI:10.1186/s12967-020-02289-w +507 CL:0000787 CL_0000787 "Memory B cells are a subtype of B cells that play a significant role in the adaptive immune response. They originate as part of B lymphocytes lineage and differentiate into memory B cells after activation by an antigen. The primary function of memory B cells is to respond rapidly to preexposure of the same antigen which originally activated it. Upon re-encountering the antigen, memory B cells can quickly differentiate into plasmablasts to generate antibodies or seed germinal centers to generate a robust immune response. + +Memory B cells can derive from mature B cells that undergo the germinal center reaction or those that differentiate in extrafollicular clusters. It is generally thought that memory B cells activated via the extrafollicular pathway are shorter-lived and produce lower-affinity antibodies, while those activated in germinal centers are longer-lived and produce high-affinity antibodies, having undergone somatic hypermutation. + +Memory B cells have a prolonged lifespan, lasting for years or even decades, enabling them to provide sustained protection against repeated or persistent infections. These cells are therefore a fundamental component of humoral immunological memory. As such, these cells are also important factors in the response to immunization/" DOI:10.1016/B978-0-12-397933-9.00007-2|DOI:10.1111/sji.12336|DOI:10.3389/fimmu.2019.01787/full|DOI:10.1038/leu.2016.226|DOI:10.1111/imr.13016 +508 CL:0000788 CL_0000788 "Naïve B cells are mature B lymphocytes that have not previously encountered a specific antigen, implying that they are ""naïve"" or ""inexperienced"". They express B-cell receptors (BCRs) on the cell surface that enable them to detect specific foreign antigens. Due to the high variability of BCRs even within the same individual, each naïve B cell is capable of recognizing a unique molecular structure, leading to an immensely diverse repertoire of these cells ready to react against a wide array of pathogenic threats. They are critical for humoral immunity as they are the precursors of antigen-specific B cells, giving rise to effector cells or memory B cells after antigen encounter and activation. + +The primary function of naïve B cells involves recognizing foreign antigens and initiating the immune response. If the B-cell receptor-engaged naïve B cell receives a proper activation signal from a helper T cell, it begins to proliferate and differentiate into plasma cells and memory B cells. Plasma cells secrete antibodies that neutralize the antigen, whereas memory B cells provide long-term immunity by remembering the specific pathogen for quicker attack upon any future invasions by the same entity. + +Furthermore, naïve B cells play a crucial role in the establishment of germinal centers (GCs), which are special zones within secondary lymphoid organs where mature B cells undergo clonal expansion, antibody class switching, and somatic hypermutation for the production of high-affinity antibodies. The maturation and changes within these GCs not only enhance the body's defense mechanisms against ongoing infections, but also promise a more rapid and effective response during subsequent encounters with the same pathogen. In summary, naïve B cells represent a stage in B cell development and serve as foundations for the adaptive humoral immune response, playing pivotal roles in antigen recognition, initiation of immune response, and long-term immunological memory. +" DOI:10.1016/B978-0-12-397933-9.00007-2|DOI:10.1007/978-981-15-3532-1_1|DOI:10.1186/s12967-020-02289-w +509 CL:0000808 CL_0000808 "The double negative 4 (DN4) thymocyte represents the fourth and final stage within the sequence of DN thymocyte development in the thymus. At this developmental stage, the cells are referred to as ""double negative"" as the cells generally do not yet express neither CD4 nor CD8 surface markers. In mice, cells committed to the αβ T cell lineage downregulate expression of CD25 and IL-7Rα (CD127), while low levels of CD4 and CD8 begin to be expressed. In humans, the developmental equivalent cell expresses CD1a, CD4, CD8α, and CD8β. + +This developmental stage follows the β-selection checkpoint in which β-chain rearrangement occurs and commitment to the αβ or γδ T cell lineage is made. DN4 thymocytes mark the transition from the double negative stages wherein the cells have neither CD4 nor CD8 markers, to the double positive stage, wherein they express both markers. DN4 thymocytes are large cells found in the subcapsule of the thymus. + +Following this stage, αβ pre-T cells reach the double positive (DP) stage followed by the single positive (SP) stage, resulting in the formation of mature T cells." DOI:10.1016/B978-012088451-3.50015-6|DOI:10.1016/B978-0-7020-6896-6.00008-9|DOI:10.1016/bs.ai.2015.09.002|DOI:10.1093/intimm/dxq457 +510 CL:0000807 CL_0000807 "The double negative 3 (DN3) thymocyte represents the third stage within the sequence of DN thymocyte development in the thymus. At this developmental stage, the cells are referred to as ""double negative"" as the cells express neither CD4 nor CD8 surface markers. In mice, these cells downregulate expression of c-kit and CD44 while continuing to express CD25. In humans, the developmental equivalent cell loses expression of CD7 and CD34 and has high expression of CD1a. + +By this stage, cells will commit to the T cell lineage, and furthermore will commit to γδ or αβ T cell development. Recombinase activating gene (RAG) enzymes initiate recombination of the TCR γ, δ, and β genes. For pre-αβ cells, an important developmental checkpoint termed β-selection occurs in which the rearranged β-chain is tested for functionality by pairing with a surrogate α chain known as pre-T α, both of which form the pre-T cell receptor (TCR). Allelic exclusion occurs, preventing further γδ rearrangements. + +Following successful gene rearrangements, the cells proliferate and continue in the developmental pathway for T cell maturation. Cells that produced non-functional pre-TCRs do not receive survival signals and will die. After the DN phase, the cells will enter the double positive (DP) phase followed by the single positive (SP) phase and develop into mature T cells." DOI:10.1016/B978-012088451-3.50015-6|DOI:10.1016/B978-0-7020-6896-6.00008-9|DOI:10.1016/bs.ai.2015.09.002|DOI:10.1093/intimm/dxq457 +511 CL:0000809 CL_0000809 "Double-positive (DP), alpha-beta thymocytes are a developmental stage in the production of mature alpha-beta T cells. These DP cells are found in the thymus. They are named 'double-positive' due to their expression of both CD4 and CD8 co-receptors on their surface, a characteristic that distinguishes them from other types of thymocytes. ‘Alpha-beta' refers to the type of T cell receptor (TCR) they express, differentiating them from gamma-delta T cells. + +In the preceding double negative (DN) phase, cells undergo an important developmental checkpoint called β-selection in which the β-chain of the TCR is rearranged and only cells expressing functional β-chains, combined with a surrogate α chain forming the pre-TCR, move forward in development. In the DP phase, cells downregulate expression of the surrogate α chain which is replaced by the α chain, which also undergoes gene rearrangements. + +This developmental stage is characterized by thymic selection processes that ultimately shape the T cell repertoire. Cells with nonfunctional TCRs undergo death by neglect, while cells expressing TCRs that bind strongly to self-peptides presented in the context of major histocompatibility complex (MHC) molecules are removed by negative selection, and cells that express TCRs that weakly interact with self-MHC are kept via positive selection. This ensures that the resulting mature T cells are able to recognize self-MHC without responding too strongly, which could result in autoimmune reactions. The CD4 and CD8 coreceptors play an important role in the selection processes, and the class of self-MHC that was recognized by the cell will dictate whether CD4 or CD8 expression remains on the cell while the other is downregulated. CD4 corresponds to the recognition of MHC class II while CD8 corresponds to MHC class I. The cell will then proceed into the single-positive (SP) phase and ultimately produce mature alpha-beta T cells." DOI:10.1016/B978-012088451-3.50015-6|DOI:10.1016/B978-0-7020-6896-6.00008-9|DOI:10.1016/bs.ai.2015.09.002|DOI:10.1016/B978-0-12-374279-7.04011-X|DOI:10.1038/nri3667 +512 CL:0000810 CL_0000810 "CD4-positive, alpha-beta thymocytes are a subset of newly developed T cells found within the thymus. This cell type is characterized by the expression of the surface proteins CD4 and T-cell receptor alpha-beta (TCR αβ). T-cell receptors are integral to the function of the T cell, allowing it to recognize and bind to specific antigens presented by other cells, while expression of the CD4 TCR coreceptor designates them as precursors to helper T cells. + +These cells represent a late stage in T cell development. Progenitor cells reach the thymus, the site of T cell maturation, and begin as double negative (DP) cells that express neither CD4 nor CD8. The cells then become double positive (DP), expressing both CD4 and CD8. The cells undergo negative and positive selection processes, in which cells are removed if they bind too strongly to self-major histocompatibility complex (MHC) molecules presenting self-peptide and cells are given survival signals if they bind weakly to self-MHC, respectively. This ensures that the resulting mature T cells are able to recognize self-MHC without responding too strongly, which could result in autoimmune reactions. The CD4 and CD8 coreceptors play an important role in the selection processes, and the class of self-MHC that was recognized by the cell will dictate whether CD4 or CD8 expression remains on the cell while the other is downregulated. CD4 corresponds to the recognition of MHC class II while CD8 corresponds to MHC class I. The cell will then proceed into the single-positive (SP) phase, producing mature, naive CD4-positive or CD8-positive, alpha-beta thymocytes. Cells are generally committed to the CD4 or CD8 lineage at this stage. These cells will complete their development by tuning their TCR threshold and proliferation, then migrate to the periphery as mature, naive T cells. + +CD4-positive, alpha-beta thymocytes, upon exiting the thymus, develop into CD4-positive T helper cells. These cells play a crucial role in the immune response. They do not directly kill infected cells or pathogens; instead, they 'help' other cells in the immune system to accomplish this. Their functions include activating and directing other immune cells, stimulating B cells to produce more antibodies, and secreting cytokines to regulate the immune response, among others." DOI:10.1155/2013/282870|DOI:10.1016/B978-012088451-3.50015-6|DOI:10.1016/B978-0-7020-6896-6.00008-9|DOI:10.1016/B978-0-12-374279-7.04011-X|DOI:10.1038/nri3667 +513 CL:0000811 CL_0000811 "CD8-positive, alpha-beta thymocytes are a subset of newly developed T cells found within the thymus. This cell type is characterized by the expression of the surface proteins CD8 and T-cell receptor alpha-beta (TCR αβ). T-cell receptors are integral to the function of the T cell, allowing it to recognize and bind to specific antigens presented by other cells, while expression of the CD8 TCR coreceptor designates them as precursors to cytotoxic T cells. + +These cells represent a late stage in T cell development. Progenitor cells reach the thymus, the site of T cell maturation, and begin as double negative (DP) cells that express neither CD4 nor CD8. The cells then become double positive (DP), expressing both CD4 and CD8. The cells undergo negative and positive selection processes, in which cells are removed if they bind too strongly to self-major histocompatibility complex (MHC) molecules presenting self-peptide and cells are given survival signals if they bind weakly to self-MHC, respectively. This ensures that the resulting mature T cells are able to recognize self-MHC without responding too strongly, which could result in autoimmune reactions. The CD4 and CD8 coreceptors play an important role in the selection processes, and the class of self-MHC that was recognized by the cell will dictate whether CD4 or CD8 expression remains on the cell while the other is downregulated. CD4 corresponds to the recognition of MHC class II while CD8 corresponds to MHC class I. The cell will then proceed into the single-positive (SP) phase, producing mature, naive CD4-positive or CD8-positive, alpha-beta thymocytes. Cells are generally committed to the CD4 or CD8 lineage at this stage. These cells will complete their development by tuning their TCR threshold and proliferation, then migrate to the periphery as mature, naive T cells. + +CD8-positive, alpha-beta thymocytes, upon exiting the thymus, develop into CD8-positive cytotoxicT cells. These cells play a crucial role in the immune response. These cells can produce cytotoxic mediators to destroy infected or cancerous cells." DOI:10.1155/2013/282870|DOI:10.1016/B978-012088451-3.50015-6|DOI:10.1016/B978-0-7020-6896-6.00008-9|DOI:10.1016/B978-0-12-374279-7.04011-X|DOI:10.1038/nri3667 +514 CL:0000815 CL_0000815 "Regulatory T cells, or Tregs, represent a vital component of the immune system, functioning to maintain immune tolerance and homeostasis. Tregs prevent excessive immune responses and autoimmunity by suppressing or downregulating proliferation or activation of other immune cells. Originating in the thymus, Tregs belong to a larger group of T cells that express CD4 protein on their surface. They can be identified by their expression of the forkhead/winged-helix transcription factor Foxp3, which is a crucial intracellular marker that controls their development and function. + +Tregs are key players in preventing autoimmune diseases, allergies, and graft-versus-host disease, a potential complication of bone marrow transplantation. By suppressing the immune response, Tregs ensure that the immune system doesn't mistakenly attack the body's own healthy tissues, or harmless substances such as pollen, or transplanted tissue. Abnormalities in Treg number or function can result in a profound dysregulation of immune homeostasis, leading to the development of various immune-mediated diseases. However, Tregs also appear to contribute to tumor development. + +Developmentally, while Tregs may emerge directly from the thymus, Tregs may also arise peripherally from conventional T cells. Thymic or ""natural"" Tregs likely arise from thymocytes that strongly recognize self-antigen and contribute to self-tolerance. Peripherally induced Tregs likely recognize foreign antigen and are likely important in maintaining tolerance to non-host antigens, such as intestinal microbiota or food allergens. Understanding the precise functions and mechanisms of regulatory T cells is a continually evolving field, with potential implications for combating autoimmunity, enhancing cancer therapy, and preventing transplant rejection." DOI:10.1146/annurev-immunol-042718-041717|DOI:10.1146/annurev-immunol-100219-020937|DOI:10.3389/fimmu.2020.616949|DOI:10.1038/nri2343|DOI:10.1111/j.1600-065X.2011.01018.x +515 CL:0000817 CL_0000817 "Precursor B cells, often abbreviated as pre-B cells, represent an intermediary stage in the development of B cells, the white blood cells that play a crucial role in the body’s adaptive immunity system. They arise from early lymphoid progenitors in the bone marrow, representing a critical point in B cell development between a pro-B cell and an immature B cell. They differ from mature B cells as they still populate the bone marrow and have yet to fully develop the distinctive B cell receptor complex. + +The primary function of precursor B cells is to undergo proliferation and rearrange their immunoglobulin light chain gene regions which ultimately forms part of the B cell receptor (BCR), an event crucial to B lymphocyte development. This process is closely monitored by the body's quality control mechanisms, ensuring all newly produced B cells have functional (and not self-reactive) receptors. This receptor editing and checking system helps to prevent autoimmune diseases, triggered when immune cells mistakenly attack the body's own cells. + +Critical mutations required for the maturation of the BCR happen in stages while the cell is a pre-B cell. Pre-B cells are initially characterized as stage called ""large pre-B cells,"" during which proliferation occurs. Additionally, heavy chain recombination is completed and the cell undergoes a checkpoint in which only cells with a functional heavy chain continue to develop. Afterwards, they transition into a ""small pre-B cell"" phase, where heavy chain rearrangement ends, and light-chain rearrangement begins. Once the B cell receptor is fully formed following heavy and light chain rearrangement, the cell is considered an immature B cell and leaves the bone marrow." DOI:10.1007/978-981-15-3532-1_1|DOI:10.1016/C2009-0-62217-0|DOI:10.1172/JCI78083|DOI:10.1016/j.febslet.2010.04.057 +516 CL:0000819 CL_0000819 "B-1 B cells represent a unique subset of B lymphocytes distinguished by their functional and phenotypic characteristics. These cells have been well studied in mice, though their human counterparts remain more difficult to characterize. These cells are predominantly found in the peritoneal and pleural cavities and play a crucial role in the body's immune response, being a part of the adaptive immune system. They are significant producers of natural antibodies even in the absence of an identifiable pathogen, making them a pivotal link between the innate and adaptive immune responses. They can be further subdivided into B-1a and B-1b cells. + +One of the defining features of B-1 B cells is the innate-like pattern of their immune response. Unlike conventional B cells (B-2 cells), which require interaction with T helper cells to initiate antibody production, B-1a B cells respond rapidly to microbial challenges, with an immediate production of low-affinity, polyreactive antibodies. These antibodies readily bind to various pathogens and provide an immediate first line of defence against invading microbes. In addition to their protective role, these antibodies also play a crucial part in maintaining homeostasis by facilitating the clearance of cellular debris and apoptotic cells. However, these antibodies can also be autoreactive and contribute to autoimmunity. Meanwhile, B-1b cells appear to produce antibodies specific to T-independent antigens. + +Moreover, B-1 B cells possess the unique ability to self-renew, akin to stem cells. This distinctive property contrasts with conventional B-2 cells, which are replenished by the bone marrow. Whereas B-2 cells primarily contribute to secondary antibody responses, B-1 B cells are known for their role in primary and early secondary immune responses. By exhibiting characteristics of both innate and adaptive immunity, B-1 B cells bridge the gap between these two divisions of the immune system, providing comprehensive protection against pathogens while maintaining body homeostasis." DOI:10.1007/978-981-15-3532-1_1|DOI:10.1038/nri2901 +517 CL:0000818 CL_0000818 Transitional stage B cells represent an intermediary stage in B cell development between immature B cells, which are produced within the bone marrow, and mature B cells, which circulate in the blood and peripheral lymphoid tissues. Transitional B cells migrate from the bone marrow to secondary lymphoid organs, usually the spleen. Transitional B cells may still undergo negative and positive selection processes to remove self-reactive B cells and to enhance survival and clonal expansion of antigen-specific cells, respectively. Transitional B cells can mature into either follicular B cells in the splenic follicles following tonic or strong B cell receptor (BCR) signaling and BAFF signaling, or marginal zone B cells between the red and white pulp of the spleen following weak BCR signaling and Notch2 signaling. Some transitional B cells themselves also possess regulatory B cell functions. DOI:10.1186/s12967-020-02289-w|DOI:10.1016/j.jaci.2013.01.046|DOI:10.1007/978-981-15-3532-1_1 +518 CL:0000816 CL_0000816 "Immature B cells, also known as Hardy fraction E, represent an intermediate stage in B cell development. +By this stage, the B cell precursors have undergone both heavy and light chain rearrangement, resulting in a diverse pool of B cell receptors (BCR). At this stage, the immature B cells undergo a stringent selection process to maintain B cell central tolerance. If an immature B cell is found to express self-reactive BCR, it can undergo receptor editing, in which rearrangement of its light chain genes is reinitiated, in an attempt to create a new, non-self-reactive BCR. If this editing process is unsuccessful and the BCR remains self-reactive, the cell can then be forced to undergo apoptosis, a process termed clonal deletion, thus preventing the production of auto-reactive, potentially harmful B cells. If the BCR recognizes self-antigen with low affinity, it may become anergic or unresponsive. Immature B cells that successfully pass these selection processes are then released from the bone marrow as transitional B cells and will complete their maturation process in secondary lymphoid organs." DOI:10.1007/978-981-15-3532-1_1|DOI:10.1038/80816|DOI:10.1038/s41467-021-27232-5 +519 CL:0000820 CL_0000820 "B-1a B cells are a subset of B cells, which are major components of the adaptive immune system, primarily responsible for humoral immunity. B-1 cells can be subdivided into B-1a and B-1b cells. Unlike their conventional B-2 B cell counterparts, B-1a B cells are self-renewing and mainly found in the peritoneal and pleural cavities, although they can also be detected in the spleen and the bone marrow. The distinguishing factor for B-1a B cells is the expression of CD5 on their cell surface, in addition to the common B cell markers, such as CD19 and CD20. + +In terms of function, B-1a B cells are crucial for the production of low-affinity, polyreactive natural antibodies, which are predominantly of the IgM class. These natural antibodies are produced even in the absence of pathogenic stimulation and play a substantial role in maintaining immune homeostasis. They can recognize highly conserved structures primarily found on the surface of common pathogens, and self-antigens released from damaged or dying cells. It appears that these autoreactive antibodies can contribute to autoimmunity. + +B-1a B cells also have a significant role in the early immune response as they can respond rapidly to pathogenic assault without requiring additional signals for activation and proliferation. This rapid response feature is mediated by the secretion of large amounts of immunoglobulins in response to Toll-like receptor (TLR) ligands. The B-1a B cells also exhibit potent phagocytic capabilities, perform antigen presentation to T cells, and exert regulatory functions through their production of IL-10, a cytokine suppressing inflammatory and autoimmune reactions." DOI:10.1007/978-981-15-3532-1_1|DOI:10.1038/nri2901 +520 CL:0000821 CL_0000821 "B-1b B cells are a subtype of B cells, which are part of the humoral immune system. B cells can be divided into B-1 and B-2 cells, and B-1 cells can be further subdivided into B-1a and B-1b cells. B-1b B cells are especially abundant in the pleural and peritoneal cavities in humans and mice, and they differ from B-1a B cells in that they lack the expression of the surface molecule CD5. + +Functionally, B-1b B cells are vital players in the immune response, particularly in providing defense against pathogens. They appear to specialize in recognizing T-independent, pathogen-associated antigens. B-1b B cells can respond to these antigens by rapidly proliferating and differentiating into cells capable of producing natural antibodies, primarily of the IgM class. These antibodies are of low affinity but broad specificity, allowing for the rapid targeting of a wide range of pathogens before the adaptive immune response has fully developed. These cells, unlike B-1a B cells, appear to undergo clonal expansion in response to antigen exposure. B-1b B cells are also thought to contribute to immunological memory." DOI:10.1007/978-981-15-3532-1_1|DOI:10.1038/nri2901 +521 CL:0000826 CL_0000826 "Pro-B cells, or progenitor B cells, are involved in the initial steps of B cell lineage development, effectors of the humoral response of the adaptive immune system. Hematopoietic stem cells in the bone marrow differentiate into pre-pro B cells, which then differentiate into pro-B cells. The early pro-B cell is also referred to as Hardy fraction B. At this stage, they begin to express B cell-specific markers, such as CD19, yet before the expression of a functional B cell receptor (BCR). This stage of development is marked by the initiation of heavy chain rearrangement, a process crucial for the formation of mature B cells. + +The initiation of the process of V(D)J recombination is initiated at this stage in B cell development. (D)J recombination is a cellular mechanism that allows genetic rearrangement to generate a diverse repertoire of antibodies. Following rearrangement of the D J heavy chain segments, the cell is considered to be in the pro-B cell stage. The successful rearrangement and expression of the Igμ heavy chain prompts the progression of pro-B cells to the pre-B cell stage, while unsuccessful rearrangements can lead to cell apoptosis, ensuring the quality control of the B cell repertoire. " DOI:10.1007/978-981-15-3532-1_1|DOI:10.1016/B978-0-12-397933-9.00007-2|DOI:10.1016/j.it.2022.01.003|DOI:10.1172/JCI78083 +522 CL:0000822 CL_0000822 "B-2 B cells, also known as conventional B cells, play a critical role in the humoral immune response. They are distinguished from B-1 cells, which can respond more rapidly and broadly to antigens. B-2 B cells are typically generated in the bone marrow, where they become mature immunocompetent cells before transporting to secondary lymphoid organs like the spleen, lymph nodes, and Peyer's patches. + +Functionally, B-2 B cells are quintessential components of the adaptive immune system. They are responsible for producing high-affinity, isotype-switched antibodies in response to antigens. In contrast to B-1 B cells that produce natural, low-affinity antibodies, B-2 B cells undergo a meticulous process of affinity maturation and clonal selection upon activation. These cells are antigen-specific and require interaction with T helper cells for proper activation. When presented with the antigen, B-2 B cells internalize, process, and present it to T cells via major histocompatibility complex II (MHC II), leading to B cell proliferation and differentiation into plasma cells or memory B cells. + +Plasma cells generated from B-2 B cells secrete vast amounts of antibodies to neutralize the invading pathogen, offering immediate protection. On the other hand, memory B cells provide long-term immunity by maintaining recognition of the antigen and prompting a rapid and potent response upon reinfection. The versatile roles of B-2 B cells in the immune response make them key players in immunization and vaccine development." DOI:10.1007/978-981-15-3532-1_1|DOI:10.1016/B978-0-12-397933-9.00007-2 +523 CL:0000827 CL_0000827 "The pro-T cell is a T cell progenitor that will develop into cells of the T lymphocyte lineage. These cells derive from the bone marrow, originally differentiating from hematopoietic stem cells, and are found in the thymus, where T cell development takes place. Pro-T cells represent the stage in T cell development prior to T cell-specific gene rearrangement. Their primary function is to proliferate and differentiate into mature T cells, which play a critical role in adaptive immunity, helping the body respond efficiently to foreign pathogens. + +In the bone marrow, hematopoietic stem cells can differentiate into common lymphoid progenitor cells. These cells are able to enter circulation and enter the thymus as thymus-seeding progenitor cells. These cells then differentiate into early thymic progenitors which proceed with T cell specification, developing from double negative (DN) to double positive (DP) to single positive (SP) T cells. Over the course of these developmental phases, the cells will commit to the T cell lineage and rearrange T cell receptor genes. In this pathway, pro-T cells can give rise to both alpha-beta and gamma-delta T cells and natural killer T (NKT) cells. + +Pro-T cells are a key constituent of the immune system, presenting a critical stage in the T cell developmental process. T cells are important players in adaptive immunity and help to initiate and orchestrate the immune response and eliminate pathogens and tumor cells. Pro-T cells are also an area of interest in the context of regenerative medicine to reconstitute T cells and adoptive T cell therapies as a potential source of T cells." DOI:10.1093/intimm/dxy051|DOI:10.1016/j.it.2020.12.004|DOI:10.1002/JLB.1MR1217-496R +524 CL:0000843 CL_0000843 "Follicular B cells are a subset of B lymphocytes that play a pivotal role in the adaptive immune response. Located primarily in the lymph nodes and spleen, they are named for their residence within the follicles of these tissues. These cells are mature, naive B cells that express IgM and IgD. Due to the high variability of B cell receptors (BCR) even within the same individual, each naive B cell is capable of recognizing a unique molecular structure, leading to an immensely diverse repertoire of these cells ready to react against a wide array of pathogenic threats. + +Follicular B cells depend upon T cells for activation via their BCR against specific antigens, and this reaction forms germinal centers in which the follicular B cells differentiate into germinal center B cells. Following class switch recombination and somatic hypermutation, these cells can differentiate into plasma cells, which secrete high-affinity antibodies, or memory B cells, which contribute to immunological memory when re-challenged by the same antigen. " DOI:10.1016/B978-0-12-397933-9.00007-2|DOI:10.1007/978-981-15-3532-1_1|DOI:10.1186/s12967-020-02289-w|DOI:10.1111/sji.12336 +525 CL:0000844 CL_0000844 "Germinal center B cells are a subset of B cells, which contribute to the humoral response of the adaptive immune system. Germinal center B cells refer to mature B cells which are in the process of being activated by cognate T helper cells via antigen presentation. This is referred to as a germinal center reaction, which typically occurs in the follicles of secondary lymphoid structures such as the spleen or lymph nodes. + +In the germinal center, antigen-exposed follicular B cells interact with follicular helper T cells (Tfh) to facilitate their maturation and function in antibody production. Tfh cells promote germinal center B cell survival and differentiation through various mechanisms, including the secretion of cytokines and interaction via cell surface molecules. Through this process, germinal center B cells proliferate and undergo affinity maturation and class switch recombination to produce high-affinity antibodies. + +Following the germinal center reaction, germinal center B cells will differente into plasma cells or memory B cells. Plasma cells are prolific producers of antibodies that target and neutralize specific antigens. Memory B cells provide long-term immunity to previously encountered pathogens, ready to mount a quick response upon re-exposure." DOI:10.1016/j.immuni.2021.07.015|DOI:10.1111/sji.12336|DOI:10.1038/nri2217|DOI:10.3389/fimmu.2018.02469 +526 CL:0000893 CL_0000893 "Thymocytes are immune cells that are found in the thymus, a small organ located in the upper chest behind the sternum. As precursors to T cells, thymocytes play a crucial role in the adaptive immune response and influence the body's ability to respond to foreign antigens. + +Thymocytes participate in thymopoiesis, resulting in the generation of mature T cells, which takes place within the thymus. This process involves the selection of T cells according to their ability to recognize and bind to an array of specific antigens without causing harm to the body's own cells. They undergo both positive and negative selection processes. During positive selection, cells capable of binding to major histocompatibility complex (MHC) molecules are selected, while the remaining cells die by apoptosis. During negative selection, cells that bind too strongly to the body's own antigens are eliminated. Both of these processes ensure that the body produces a diverse range of T cells that can fight infections without harming the body." https://www.ncbi.nlm.nih.gov/books/NBK27123/|DOI:10.1038/nri3667|DOI:10.1016/B978-0-12-374279-7.04011-X|DOI:10.3389/fimmu.2022.885280|DOI:10.3389/fimmu.2023.1197066 +527 CL:0000896 CL_0000896 "Activated CD4-positive, alpha-beta T cells are one of the subset of T-lymphocytes that play a crucial role in the adaptive immune system by orchestrating many aspects of the immune response. They are characterized by the simultaneous expression of CD4 membrane glycoprotein and T cell receptor alpha-beta (TCR αβ), whilst their activation is defined by their engagement with a specific antigen, typically presented by antigen-presenting cells (APCs) within the context of major histocompatibility complex (MHC) class II molecules. + +Activation triggers these T cells to differentiate into several distinct types of effector T-cells, including T-helper (Th) cells and regulatory T cells (Tregs). T-helper cells, including Th1, Th2, Th17, and Th-follicular cells, support other immune cells by releasing potent cytokines. Depending on the specific subset they differentiate into, they may aid in the clearance of intracellular pathogens (Th1 cells), facilitate B cell antibody production and eosinophil activation (Th2 cells), enhance neutrophil response (Th17 cells), or assist in the formation and maintenance of memory B cells and plasma cells (Tfh cells). + +In contrast, the activated CD4-positive, alpha-beta T cells that turn into regulatory T cells play a key immunosuppressive role in the immune system by maintaining homeostasis and tolerance to self-antigens, preventing autoimmune diseases. However, they can also diminish anti-tumor immune responses and promote chronic infectious disease. " DOI:10.1038/nri3152|DOI:10.1155/2012/925135|DOI:10.1146/annurev-immunol-030409-101212|DOI:10.3389/fimmu.2012.00051|DOI:10.1186/s12943-020-01234-1 +528 CL:0000895 CL_0000895 "The naive thymus-derived CD4-positive, alpha-beta T cell is an important immune cell type in the adaptive immune system. Originating in the thymus, these lymphocytes differentiate from immature thymocytes, a process involving gene rearrangement leading to the expression of a unique alpha-beta T-cell receptor (TCR) on their surface. This cell type is classified as ""naive"" because it has yet to encounter its cognate antigen, which subsequently activates the T cell. The naive state is characterized by readiness for activation and a lack of any memory of past antigen encounters. + +Once the cell completes its developmental program in the thymus, it is exported to the periphery where it circulates throughout the body as a recent thymus emigrant. The cell continues to undergo post-thymic maturation until it develops into a mature naive CD4+ T cell. The naive cell is able to respond to its cognate antigen. + +CD4+ T cells are important in the initiation of the immune response. Upon antigen exposure, they undergo a process of activation, proliferation, and differentiation. Activation occurs when the T cell receptor on the naive CD4+ T cell binds to the antigen-major histocompatibility (MHC) class II complex on an antigen-presenting cell and additional costimulatory signals are received. Once activated, naive CD4+ T cells proliferate extensively and differentiate into specific subsets of effector T cells which include T helper 1 (Th1), T helper 2 (Th2), T helper 17 (Th17) cells, and follicular helper T (Tfh) cells, each aiding in a tailored immune response to varying types of pathogens. Th1 cells are involved in the combat against intracellular pathogens, Th2 cells defend against parasites, Th17 cells provide immunity against extracellular bacteria and fungi, and Tfh cells play a role in B-cell activation and the production of antibodies, thus being instrumental in humoral immune responses. " DOI:10.1146/annurev-immunol-103019-085803|DOI:10.1038/nri3152|DOI:10.1155/2012/925135|DOI:10.1038/s41577-018-0044-0|DOI:10.1016/j.coi.2017.12.006 +529 CL:0000894 CL_0000894 "The double negative 1 (DN1) thymic pro-T cell, also referred to as the early T lineage precursor, is the first cell to arrive in the thymus from the bone marrow that will develop into cells of the T cell lineage. These cells are referred to as double negative due to their lack cell surface expression of CD4 and CD8. In mice, they express c-kit and CD44 but not CD25, while the human equivalent cells express CD34 and CD7 but not CD1a. These cells are not yet committed to the T cell lineage. + +Once the DN1 cell enters the thymus, it begins to respond to the Notch signaling environment and begins to activate genes related to T cell development and to proliferate. The markers used to define this stage differ between humans and mice. In humans, DN1 cells express CD34; in mice, the cells express c-kit and CD44. + +In mice, these cells can go on to the DN2-4 stages, to the double positive stage, then to the single positive stage, thereby producing αβ T cells such as CD4+ cells, CD8+ cells, regulatory T cells, or invariant natural killer T cells; throughout the developmental process, they may also branch off to form γδ T cells instead." DOI:10.1016/bs.ai.2015.09.002|DOI:10.1016/B978-0-7020-6896-6.00008-9|DOI:10.1016/B978-012088451-3.50015-6|DOI:10.1016/j.smim.2022.101662 +530 CL:0000898 CL_0000898 "Naive T cells, a key component of the adaptive immune system, are T cells that have successfully completed the thymic selection process and have left the thymus but have not yet encountered an antigen in the peripheral lymphoid tissues. Biologically, they are defined by their antigen-inexperienced status, their ability to differentiate into effector and memory phenotypes upon stimulation, and the expression of specific cell surface markers, including CD45RA in humans. + +Naïve T cells play a vital role in responding to novel infections. Emerging from the thymus, they circulate in the bloodstream and peripheral lymphatic system, patrolling for their cognate antigen. Upon encountering an antigen presented to them by antigen-presenting cells (APCs) such as dendritic cells, naive T cells rapidly differentiate into effector T cells that target the foreign body or pathogen. Two common types of effector T cells are helper T cells (Th) that assist other white blood cells in immunologic processes, and cytotoxic T cells (Tc) that destroy virus-infected cells and tumor cells. + +Importantly, antigen exposure not only results in the expansion of the effector T cell population but also the creation of memory T cells. Memory T cells provide long-term immunity by remembering antigens from previous exposures and mount a rapid and robust response when re-exposed to the same antigen. Thus, the high specificity and adaptive nature of the immune response hinge on these naive T cells, making them pivotal in the development and success of immunization strategies and therapies." DOI:10.1038/s41577-018-0001-y|DOI:10.1016/B978-012088451-3.50015-6|https://www.ncbi.nlm.nih.gov/books/NBK27118/ +531 CL:0000897 CL_0000897 "The CD4-positive, alpha-beta memory T cell is a specialized type of immune cell that belongs to the broader classification of T lymphocytes. These unique cells play a pivotal role in the body's adaptive immune system, providing long-term immunity against past infections or vaccinations. As part of the memory T cell subset, they are characterized by their ability to respond upon re-exposure to a previously encountered antigen with a quicker and more robust response. + +CD4-positive, alpha-beta memory T cells are defined by the expression of CD4 surface markers and alpha-beta T-cell receptors. CD4 assists in antigen recognition and aids the T cell in communicating with other types of immune cells. Alpha-beta refers to the specific heterodimeric T-cell receptor (composed of an alpha and a beta chain) that recognizes a unique antigenic peptide, distinguishing these cells from gamma-delta T cells. As memory cells, these cells are different from naïve T cells, which have not yet encountered their specific antigen. + +Their primary function is immunosurveillance and contributing to long-lasting immunological memory. Upon subsequent encounters with their cognate antigen, these memory T cells can rapidly multiply and differentiate into effector T cells, triggering a quick, more significant immune response. This includes the production of effector molecules such as cytokines that can directly act against the invading pathogen or activate and recruit other immune cells. " DOI:10.1038/s41590-023-01510-4|DOI:10.1615/critrevimmunol.2014010373|DOI:10.1111/imm.12929|DOI:10.3390/cells9030531|DOI:10.3389/fimmu.2018.02394 +532 CL:0000900 CL_0000900 "The naive thymus-derived CD8-positive, alpha-beta T cell is an important immune cell type in the adaptive immune system. Originating in the thymus, these lymphocytes differentiate from immature thymocytes, a process involving gene rearrangement leading to the expression of a unique alpha-beta T-cell receptor (TCR) on their surface. This cell type is classified as ""naive"" because it has yet to encounter its cognate antigen, which subsequently activates the T cell. The naive state is characterized by readiness for activation and a lack of any memory of past antigen encounters. + +Once the cell completes its developmental program in the thymus, it is exported to the periphery where it circulates throughout the body as a recent thymus emigrant. The cell continues to undergo post-thymic maturation until it develops into a mature naive CD8+ T cell. The naive cell is able to respond to its cognate antigen. + +CD8+ T cells detect and eliminate cells presenting foreign or abnormal antigens in the context of major histocompatibility complex (MHC) class I, making them important in the response to intracellular pathogens, such as viruses or bacteria that infect host cells, as well as in cancer. Upon contact with an antigen presented by an antigen-presenting cell, these naive T cells become activated and differentiate into effector cells capable of identifying and destroying infected or malignant cells. These resultant cytotoxic T cells can release cytotoxic mediators such as perforin and granzymes, which induce apoptosis in the target cells." DOI:10.1155/2013/282870|DOI:10.1016/j.immuni.2011.07.010|DOI:10.1038/s41577-021-00574-3|DOI:10.1016/j.coi.2017.12.006 +533 CL:0000906 CL_0000906 "Activated CD8-positive, alpha-beta T cells, also known as cytotoxic T cells, are a specialized subset of T cells distinct for their contribution to immunity. These cells originate from CD8-positive, alpha-beta T cell precursors and undergo activation upon the recognition of specific antigens presented by MHC class I molecules, primarily associated with intracellular pathogens such as viruses. T-cell activation typically necessitates two signals: one from the T cell receptor (TCR) recognizing the MHC-antigen complex and the other from the binding of co-stimulatory molecules. + +The main function of activated CD8-positive, alpha-beta T cells lies in their ability to induce apoptosis, or programmed cell death, in infected or malignantly transformed cells. It is the CD8-positive interaction with MHC class I that equips these cells with the ability to detect and destroy infected host cells. Following activation, these cells differentiate into two cell types: cytotoxic T lymphocytes (CTLs), which destroy pathogen-infected cells directly, and memory T cells, which persist in the body to expedite the immune response upon re-exposure to the same pathogen. + +Moreover, these cells play a crucial role in the immune response against tumors. They recognize and bind to tumor antigens, thereby initiating the destruction of cancer cells. The presence of activated CD8-positive, alpha-beta T cells in tumors often correlates with a better prognosis in a variety of cancers. " DOI:10.1016/j.immuni.2011.07.010|DOI:10.1038/s12276-023-01105-x|DOI:10.1038/s41416-020-01048-4|DOI:10.1016/j.csbj.2018.11.004|DOI:10.1016/j.eclinm.2021.101134 +534 CL:0000899 CL_0000899 "T-helper 17 cells, also known as Th17 cells, belong to a subset of T cells which produce interleukin 17 (IL-17). They are part of the body's adaptive immune system and play a decisive role in host defense against bacteria and fungi, especially those that colonize mucosal surfaces. Th17 cells are identified by their unique expression of the retinoid-related orphan receptor γt (RORγt) transcription factor, which drives the production of the hallmark cytokine IL-17. Moreover, these cells have the capability to produce other inflammatory cytokines, such as IL-22, IL-21, and tumor necrosis factor-alpha (TNF-a). + +Th17 cells are primarily involved in the defense against pathogens that are not adequately controlled by Th1 or Th2 immune responses. They demonstrate strong defence mechanisms against extracellular pathogens by triggering an inflammatory response which recruits neutrophils and macrophages to the site of infection. A major role of Th17 cells is the maintenance of barrier integrity in the intestine, allowing for a controlled immune response that balances host defense with limitation of tissue damage. + +However, the dysregulation of Th17 cells may contribute to the pathogenesis of autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. A greater understanding of these cells is crucial because they offer promising targets for the treatment of such immune-mediated diseases. Therapeutics that block IL-17 or IL-23 (which maintains Th17 cell responses) are being developed and have shown effectiveness in psoriasis, highlighting the potential for Th17 targeted therapy in other diseases. " DOI:10.1016/j.ajpath.2020.07.010|DOI:10.1111/j.1600-065X.2008.00628.x|DOI:10.1016/j.ajpath.2012.03.044|DOI:10.1155/2014/651503 +535 CL:0000909 CL_0000909 "The CD8-positive, alpha-beta memory T cell is a critical component of the immune system, playing a significant role in the body's adaptive immune response against viral and intracellular bacterial infections. This particular subtype of T cell is characterized by the expression of the CD8 co-receptor and the alpha-beta T cell receptor (TCR). These cells are part of the broader group of memory T cells, which are long-lived cells that have previously encountered and responded to a specific pathogen, thereby ""remembering"" the pathogen for a faster and more effective response if the same pathogen invades the body again. This prompt response is characterized by rapid proliferation and immediate capability to execute effector functions, such as the production of antiviral and anti-tumor cytotoxic responses. Due to their 'memory,' these cells can provide the immune response this speed and effectiveness, which is at a notably higher level compared to the primary immune response of naive T cells. + +In disease states, CD8-positive, alpha-beta memory T cells can be pivotal in host defense. For instance, in viral infections, these memory T cells can rapidly expand to create a large pool of effector cells that can kill infected cells, thereby controlling and eliminating the infection. Their importance is also noted in the context of vaccination strategy, as one of the primary goals of vaccination is to establish a robust population of memory T cells, which can confer long-term immunity against specific pathogens. However, dysregulation in memory T cell responses can contribute to autoimmune or other chronic inflammatory diseases by supplying persistent immunological attacks against self-antigens or innocuous antigens. " DOI:10.1016/j.imlet.2017.02.012|DOI:10.1038/nri2251|DOI:10.3389/fimmu.2018.02692|DOI:10.1016/j.smim.2020.101435|DOI:10.1038/s41590-021-00949-7 +536 CL:0000907 CL_0000907 "Central memory CD8-positive, alpha-beta T cells, commonly referred to as Tcm cells, are a distinctive subset of immune cells within the broader classification of T lymphocytes. They play a pivotal role in the human immune response by cultivating long-lasting immunity against pathogens. CD8-positive indicates the presence of CD8 protein on the cell surface, which acts as a co-receptor with the T-cell receptor (TCR) to recognize and interact with antigens presented by MHC class I molecules on infected or abnormal cells. The alpha-beta refers to the TCR type on these cells—these receptors are comprised of an alpha and a beta chain, which serve as a recognition site for antigens. + +Tcm cells, once activated by an antigen, undergo a clonal expansion phase, leading to the creation of a significant number of effector T cells that can directly destroy the infected or anomalous cells. First contact with an antigen transforms naive CD8-positive T cells into a mixed population consisting of cytotoxic T cells (Tc cells) and memory cells including Tcm cells. While Tc cells are chiefly responsible for the immediate response to infection, Tcm cells hold important immunological 'memories', which allow for a rapid and efficient response to future encounters with the same antigen. + +Furthermore, a standout feature of central memory CD8-positive, alpha-beta T cells is their ability to circulate through the lymphoid organs (e.g., lymph nodes), contrary to effector memory T cells which traffic through non-lymphoid tissues. This strategic positioning aids in rapid detection of the previously encountered pathogen. In response, Tcm cells proliferate extensively and differentiate into cytotoxic T cells, expediently minimizing the spread of infection." DOI:10.1146/annurev.immunol.22.012703.104702|DOI:10.1111/imm.12929|DOI:10.1016/j.immuni.2018.02.010|DOI:10.1111/imr.12087|DOI:10.1038/s41467-019-12319-x +537 CL:0000913 CL_0000913 "Effector memory CD8-positive, alpha-beta T cells, also known as TEM cells, are a critical subset of T cells, the warriors of the immune system. They have a unique role in fighting off infections, demonstrating rapid and enhanced immune responses when exposed to a previously encountered antigen. This cell type has the ability to remember prior exposure, hence the term ""memory” cells, and mounts an intensified defense during subsequent encounters, helping to fend off disease quickly and effectively. + +These cells originate from naive T cells that become activated when they encounter a novel antigen presented by antigen-presenting cells (APCs). Once activated, they undergo clonal expansion, differentiating into cytotoxic T cells that help to neutralize the perceived threat. After the resolution of the infection, most of these effector T cells will apoptose, however, some persist in the body as ‘memory’ cells. These effector memory T cells are fast-acting and provide robust protection against pathogens to which the host has been previously exposed. + +Effector memory CD8-positive, alpha-beta T cells are unique in several ways. They lack lymph node homing receptors, meaning that they are mainly found in peripheral tissues and circulation, ready to combat infections at the site. They express high levels of effector molecules such as perforin and granzymes which can induce apoptosis in target cells. Additionally, they can rapidly produce cytokines including interferon-gamma and tumor necrosis factor-alpha in response to antigen stimulation. As such, these cells serve a vital role not only in defense against microbial pathogens but also in various immunopathological diseases and in cancer immunosurveillance. These characteristics of proliferation, rapid response, and effector functions render the effector memory CD8-positive, alpha-beta T cells a key player in the immune responses." DOI:10.1146/annurev.immunol.22.012703.104702|DOI:10.1111/imm.12929|DOI:11/8/549/6746817|DOI:10.3389/fimmu.2018.02692|DOI:10.1073/pnas.2008571117 +538 CL:0000908 CL_0000908 "The CD8-positive, alpha-beta cytokine secreting effector T cells play pivotal roles in the body's defense against viral, bacterial, and parasitic infections. These cells are a specialized subtype of T lymphocytes that express the CD8 glycoprotein on their surface and they are distinguished by the secretion of specific cytokines and the use of unique T-cell receptors (TCRs) comprised of alpha (α) and beta (β) chains. + +The primary function of these cells includes identifying and eliminating the cells that are infected by pathogens or somehow impaired. They achieve this through their TCRs, which allows them to recognize antigenic peptides presented on the surface of target cells by Major Histocompatibility Complex (MHC) class I molecules. When these cells recognize their specific antigen, they become activated, initiating the release of potent cytokines and cytotoxic substances which facilitate in the destruction of the infected or damaged cells. + +Remarkably, these T cells are also involved in shaping the immune response. Their cytokine secretion upon activation is vital in signaling other immune cells to the site of infection and moderating their activities. For example, their release of Interferon-gamma (IFN-γ) enhances the ability of macrophages to destroy pathogens and also inhibits the replication of viruses. Moreover, these effector T cells can also transform into memory T cells after the initial immune response. " DOI:10.1046/j.1365-2567.2001.01193.x|DOI:10.1038/s12276-023-01105-x|DOI:10.1016/j.immuni.2011.07.010|DOI:10.1155/2015/849573|DOI:10.1038/nature25144 +539 CL:0000914 CL_0000914 "The Immature Natural Killer T (NKT) cell is a precursor cell within the broader family of T lymphocytes, sitting at the intersection of the adaptive and innate immune responses. Notably, these are characterized by their unique T cell receptor (TCR) arrangement and an inherent ability to recognize glycolipid antigens presented by the cellular protein CD1d. Immature NKT cells develop in the thymus from immature thymocytes and can complete their maturation program either in the thymus or in the periphery. + +Immature NKT cells undergo a maturation process over several stages, typically identified as stage 0 (immature) to stage 3 (mature). Their maturation process is driven by specific signaling pathway activations and gene expression patterns, leading to phenotypic and functional changes in their identity to respond effectively to a variety of pathogens. During this maturation, the cells upregulate various cell surface receptors, such as NK1.1, and cytokines. + +Functionally, immature NKT cells are directly implicated in the immune response despite their earlier stage in the cellular life cycle. They can exert effector functions such as cytotoxicity and cytokine production, crucial in combating infectious pathogens and tumorigenic cells. Moreover, they bridge the innate and adaptive immune system due to their capability of rapid activation and secretion of an array of cytokines, influencing surrounding cells, such as driving T-cell differentiation or activating NK cells. " DOI:10.1038/nri2116|https://www.ncbi.nlm.nih.gov/books/NBK532332/|DOI:10.1038/ni.1841 +540 CL:0000911 CL_0000911 "Effector T cells, also known as Teff cells, are a subtype of T cells that actively respond to a stimulus, such as a microbial pathogen. These cells form an integral part of the adaptive immune system, a defense mechanism that identifies, attacks, and develops immunity against specific foreign bodies or antigens. Effector T cells are generated from naive T cells upon antigen exposure. + +Effector T cells can be further classified into specific subsets according to their function and cytokine profile. These include T-helper cells (Th1, Th2, Th17), T-follicular helper (Tfh) cells, and cytotoxic T-lymphocytes (CTL). Th1 cells facilitate the eradication of intracellular pathogens through the activation of macrophages and enhancement of cytotoxic T lymphocyte activity. Th2 cells play a crucial role in the expulsion of parasites from the body by promoting eosinophil function and antibody production. Th17 cells protect against fungal and bacterial infections primarily at mucosal surfaces. Tfh cells assist B cells in the production of high-affinity and long-lived antibodies. CTLs, on the other hand, are known for their ability to recognize and kill pathogen-infected cells and cancer cells. + +In order to perform their functions, effector T cells travel to the site of infection or inflammation. They are primarily controlled by the production of various soluble factors, including cytokines and chemokines. Once activated, they become highly potent killers and can directly engage with cells to temper their activity or encourage their destruction. Notably, effector T cells perish after their immune response, leaving behind memory T cells to provide long-lasting protection. " DOI:10.1038/s41392-023-01471-y|DOI:10.12703/r/10-30|DOI:10.1038/nri2295|DOI:10.1016/j.immuni.2014.10.004|DOI:10.1038/nri819 +541 CL:0000934 CL_0000934 "The CD4-positive, alpha-beta cytotoxic T cells, also referred to as CD4+ αβ T cells, play multifaceted roles in the human immune defense system. Despite the CD4 receptor traditionally being associated with helper T cells, which assist other immune cells in their functions, this particular cell type possesses cytotoxic capabilities. Combining this with its helper activities, the CD4-positive, alpha-beta cytotoxic T cell, showcases a remarkable duality of immunological roles, making it indispensable to maintaining cellular homeostasis. + +The chief function of CD4-positive, alpha-beta cytotoxic T cells is to identify and eliminate pathogen-infected cells and cancerous cells. They achieve this through their cytotoxic capabilities, which mirrors the function of their CD8+ counterparts. Upon interaction with an antigen presented by Major Histocompatibility Complex (MHC) class II molecules on the surface of an antigen-presenting cell, the CD4+ αβ T cell becomes activated. Subsequently, the cytotoxic T cell releases toxic granules into the infected cell, triggering programmed cell death or apoptosis, thereby stopping the spread of the infection or proliferation of tumor cells. + +Moreover, the CD4-positive, alpha-beta cytotoxic T cells also function as immunoregulatory cells. They can secrete specific cytokines that influence the immune response in a context-specific manner. This regulatory function is crucial in preventing excessive or misdirected immune responses that could result in autoimmune disorders or chronic inflammation. " DOI:10.3389/fimmu.2017.00194|DOI:10.1016/j.immuni.2021.11.015|DOI:10.3389/fimmu.2022.867189|DOI:10.1038/s41417-020-0183-x|DOI:10.1186/ar1703 +542 CL:0000921 CL_0000921 "The type I NK T cell, also known as invariant Natural Killer T (iNKT) cell, is a unique subset of T lymphocytes that share properties with both conventional T cells and Natural Killer (NK) cells. These cells are predominantly involved in immune responses against infections and tumors. They have an idiosyncratic T-cell receptor (TCR), which generally recognizes lipids and glycolipids, rather than proteins, which is the central distinguishing attribute that segregates them from conventional T cells. + +Functionally, type I NK T cells act as an intermediary between the innate and adaptive immune system. Upon activation, they function rapidly by producing large quantities of different types of cytokines and chemokines that can directly kill infected or malignant cells and recruit and activate other immune cells. In this way, they create a bridge between the initial innate immune responses and the consequent adaptive immune responses to various challenges. Notably, the cytokines they produce can influence the function of other immune cells, which allows iNKT cells to regulate both cell-mediated and humoral immune responses. + +The type I NK T cell also has a critical role in immune regulation and tolerance. Evidence suggests that they play a protective role in autoimmune diseases and allergies by suppressing overly active or inappropriate immune responses. Moreover, these cells have the potential to either enhance or suppress immune responses, depending on the cytokine environment, the antigen presented, and the intracellular lipid antigen presentation pathway." DOI:10.3389/fimmu.2023.1176724|DOI:10.12688/f1000research.21378.1|DOI:10.3389/fimmu.2018.01393|DOI:10.1038/nri3369|DOI:10.1126/sciimmunol.abj8760 +543 CL:0000940 CL_0000940 "Mucosal invariant T (MAIT) cells represent a unique subset of T cells that are primarily found within the mucosal tissues such as the lungs, guts, and liver. They are characterized by their restriction to the highly evolutionarily conserved Major Histocompatibility Complex (MHC) class I-related protein, MR1 that presents bacterial vitamin B-derived antigens. This MR1 restriction confers MAIT cells with the ability to react to a wide array of microbes, from bacteria to fungi and other pathogenic microorganisms, in a highly conserved and evolutionarily efficient manner. + +Functionally, MAIT cells play important roles in innate and adaptive immunity. They exhibit innate immune cell-like characteristics due to their ability to respond rapidly to stress signals and infected cells without the need for previous exposure or memory response typical of the adaptive immune system. After activation, MAIT cells are known to produce a wide variety of effector cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-17 (IL-17) depending on the cytokine milieu of the surrounding environment. This ability to produce different cytokines enables MAIT cells to participate in various immune responses including anti-bacterial immunity, tissue repair, and inflammation regulation. +" DOI:10.1038/s41577-019-0191-y|DOI:10.3389/fimmu.2020.01014|DOI:10.1093/intimm/dxab070|DOI:10.1073/pnas.1222678110|DOI:10.3389/fimmu.2017.01540 +544 CL:0000936 CL_0000936 "Early lymphoid progenitors, also known as lymphoid-primed multipotent progenitors (LMPPs), are a pivotal cell type in the hematologic system, specifically within the immune cell lineage. These cells, as their name suggests, serve as precursors to cells of the lymphoid lineage. They exist in the developmental stage before lymphocyte lineage commitment and play an important role in the life cycle of immune cells, bridging the gap between hematopoietic stem cells and mature, differentiated immune cells. + +In the bone marrow, hematopoietic stem cells give rise to early lymphoid progenitors. Early lymphoid progenitors are characterized by their potential to differentiate into multiple lymphoid lineages. Upon receiving different differentiation signals, these progenitor cells can give rise to B cells, T cells, natural kill (NK) cells, and some dendritic cells. The function and resulting lineage of these multipotent progenitors is guided by complex signaling and transcription factor networks, that adjust in response to physiological and pathological conditions. + +Early lymphoid progenitor cells are an important part of the process by which lymphoid cells are produced and replenished in the body, which is essential for an effective immune response. Aberrations in early lymphoid progenitor cell development or function can lead to several health conditions, including immunodeficiency and leukemia. Therefore, a proper understanding of these early lymphoid progenitors is integral for appreciating the intricate developmental pathways in the immune system and for developing targeted therapies for related diseases." DOI:10.15252/embj.201798443|DOI:10.1016/B978-0-323-04404-2.10002-8|DOI:10.1016/j.exphem.2021.09.007|DOI:10.1016/j.coi.2016.01.009 +545 CL:0000954 CL_0000954 The small pre-B-II cell, also known as Hardy fraction D, is an intermediate stage in B cell development and maturation, contributing significantly to the immune response by generating diverse repertoires of antibodies. Small pre-B-II cells are located in the bone marrow. These cells are formed following proliferation of large pre-B-II cells which have undergone a checkpoint for the successful rearrangement of the Ig heavy chain and cell surface expression of the pre-B cell receptor (BCR). At the small pre-B-II cell stage, cell surface expression of the pre-BCR is lost and rearrangement of the light chain is initiated following expression of the Rag1/2 genes. The integrated IgM BCR is then expressed on the cell surface following successful light chain recombination and protein expression. At this point, the cell enters the immature B cell stage. DOI:10.1007/978-981-15-3532-1_1|DOI:10.4049/jimmunol.170.3.1354|DOI:10.1016/B978-0-12-397933-9.00007-2 +546 CL:0000955 CL_0000955 Pre-B-II cells are a precursor cell in the development of B lymphocytes, effectors of the humoral immune response. These cells are at an intermediate stage of B cell maturation and are located in the bone marrow. Cell surface expression of the IL-2R α-chain, or CD25, is upregulated at this stage. The pre-B-II stage is broken down into two further developmental stages, the large pre-B-II and small pre-B-II stages, both of which contribute to the development of a functional B cell receptor (BCR) required for antigen recognition. The large pre-B-II stage is characterized by proliferation following an important checkpoint in B cell development, the expression of the pre-BCR following successful heavy chain gene recombination. The small pre-B-II stage is characterized by downregulation of surface pre-BCR expression and the initiation of light chain rearrangement. Following successful light chain rearrangement, the cell may then express the IgM BCR and enters the next stage of development, the immature B cell stage. DOI:10.1007/978-981-15-3532-1_1|DOI:10.4049/jimmunol.170.3.1354 +547 CL:0000970 CL_0000970 "Unswitched memory B cells are a subcategory of memory B cells that have not undergone class switch recombination (CSR). B cells are a vital part of the immune system and they have an essential role in the production of antibodies, also known as immunoglobulins. Unswitched memory B cells express IgM with or without IgD immunoglobulin isotypes on their surface. They contribute to long-term immunological memory following exposure to an antigen by retaining their reactivity to that antigen, allowing for a faster response upon re-exposure to that antigen. + +The origin and function of unswitched memory B cells remains an ongoing subject of research. They may develop from germinal center reactions or independently of them. They appear to complement the function of class-switched memory B cells in that unswitched memory B cells can also become reactivated during antigenic rechallenge, but can adapt to the new challenge by undergoing somatic hypermutation and class-switch recombination themselves if required. + +Unswitched memory B cell populations appear to be altered in autoimmune diseases such as systemic lupus erythematous or rheumatoid arthritis, suggesting that they may play an important role in these disease states." DOI:10.3389/fimmu.2023.1308378|DOI:10.1038/leu.2016.226|DOI:10.1111/imr.13016|DOI:10.3389/fimmu.2024.1326823 +548 CL:0000957 CL_0000957 The large pre-B-II cell, also referred to as Hardy fraction C’, is an important developmental stage in the formation of B cells, which are responsible for producing antibodies to specific antigens. These cells are located in the bone marrow and represent an intermediate stage following the pre-B-I stage and preceding the small pre-B-II stage. At the large pre-B-II cell stage, cells express the rearranged heavy chain on the cell surface as part of the pre-B cell receptor (BCR). This represents an important checkpoint in the normal development of B cells. Expression of the pre-BCR on the cell surface induces cell proliferation, producing an expanded population of small pre-B-II cells. DOI:10.1007/978-981-15-3532-1_1|DOI:10.4049/jimmunol.170.3.1354|DOI:10.1016/j.febslet.2010.04.057 +549 CL:0000982 CL_0000982 "IgG plasmablasts are a subset of B cells which are a crucial component of the adaptive immune system. Plasmablasts develop from mature B cells which have encountered antigen and are in the process of being activated. These B cell blasts may differentiate into short-lived plasmablasts, which can continue to divide and to secrete low-affinity antibodies, allowing for a rapid response to antigens. These cells may further differentiate into plasma cells in the bone marrow which secrete large amounts of high-affinity antibodies. + +In response to antigens, follicular T cells deliver antigen-dependent signals to cognate mature B cells. This leads to the activation of the cognate B cells and their development into B cell blasts which can undergo class switch recombination. These cells migrate to extrafollicular sites and differentiate into plasmablasts which secrete antibodies which tend to exhibit low or moderate affinity for the antigen as the cells have not yet undergone somatic hypermutation. Some plasmablasts may undergo class switch recombination to produce IgG antibodies, which may contribute to robust initial IgG titers following an infection, although this may not necessarily lead to long-lasting immunity. + +IgG antibodies are the most abundant form of antibodies in the body and is considered to be the primary immunoglobulin isotype involved in the response to inflammation. IgG is typically found in monomeric form in the serum and it can be further subclassified as IgG1, IgG2, IgG3, and IgG4. IgG can function as an opsonin, triggering phagocytosis or antibody-dependent cell-mediated cytotoxicity of pathogens, and it can also trigger the classical complement cascade to enhance pathogen clearance. " DOI:10.1038/nri3795|DOI:10.1016/j.immuni.2020.11.006|DOI:10.1007/978-981-15-3532-1_1|DOI:10.1111/sji.12336|DOI:10.1016/j.immuni.2020.11.006 +550 CL:0000972 CL_0000972 "Class switched memory B cells are a specialized type of B lymphocyte, a critical component in the adaptive immune system. These cells play a fundamental role in maintaining long-term immunity and providing a more effective and rapid response during reinfection. These cells are primed during the first exposure to antigen and are able to produce specific IgG, IgA, or IgE antibodies to that antigen. Upon re-exposure to that antigen, class switched memory B cells are able to respond quickly to that antigen, thus contributing to immunological memory. + +Class switched memory B cells originate from activated B cells that have undergone class switch recombination and somatic hypermutation in the germinal centers of secondary lymphoid organs, the sites where antigen-stimulated B cells proliferate and differentiate. Class switching is a process that changes the heavy-chain constant region of the antibody molecule, thus switching the antibody's class or isotype from IgM to IgG, IgA, or IgE. Cells that have undergone the germinal center reaction may remain in the germinal center, become an antibody-secreting plasma cell, or become a long-lived memory B cell. + +Functionally, class switched memory B cells are crucial for providing protection against previously encountered pathogens. Upon secondary exposure to the same antigen, these cells can quickly initiate a rapid and potent immune response, marked by the production of high-affinity, isotype-switched antibodies. In addition, class switched memory B cells exhibit enhanced antigen-presenting capabilities, further supporting their role in immune response. " DOI:10.1111/imr.12640|DOI:10.1146/annurev-immunol-041015-055531|DOI:10.1111/imr.13016|DOI:10.3389/fimmu.2019.01787|DOI:10.1038/nri3802 +551 CL:0000979 CL_0000979 "The IgG memory B cell is a critical component of the adaptive immune response, serving to protect the body from microbial and viral infections by producing specific antibodies against antigens that the body has already encountered. These cells are a subpopulation of class switched memory B cells that express immunoglobulin G (IgG) on their surface. IgG memory B cells play a crucial role in secondary immune responses. + +During the initial encounter with an antigen, mature B cells are activated and can undergo somatic hypermutation and class switch recombination in germinal center reactions, resulting in the ability to produce high-affinity antibodies. These cells can develop into antibody-producing plasma cells to respond to the antigen during the primary encounter, or they can develop into long-lived memory B cells which contribute to immunological memory. These cells respond during subsequent exposures to the same antigen. + +During these subsequent responses, IgG memory B cells appear to differentiate into antibody-secreting cells without needing to interact with a germinal center, or they can seed new germinal centers. This response is markedly faster than the primary response. Notably, the subdivision of memory B cells based solely on the antibody isotypes they produce may not be indicative of their function. Expression of other markers, such as CD80 and PD-L2, can further distinguish the functions of these cells in terms of whether the cells will become antibody-secreting cells or seed germinal centers." DOI:10.3389/fimmu.2019.01787|DOI:10.1111/sji.12336|DOI:10.1111/imr.13016|DOI:10.1111/imr.12640|DOI:10.1038/nri3802 +552 CL:0000974 CL_0000974 "Long-lived plasma cells are the effector cells of the humoral immune response and serve a crucial role in maintaining long-term, antigen-specific immunity. These cells result from the differentiation of mature naive B cells, which activate upon encountering antigens. Once activated, mature B cells can differentiate into short-lived plasma cells that provide immediate protection or long-lived plasma cells that sustain immunity over time. The primary function of long-lived plasma cells is the ongoing production and secretion of large quantities of high-affinity antibodies specific to the antigen encountered during the initial immune response. + +Long-lived plasma cells are generated in the spleen and migrate to the bone marrow, residing in niches that persist and provide long-term immunity. They can persist for years or even a lifetime in the body, continually secreting antibodies to ensure continued protection against the specific pathogen. These memory cells are a cornerstone of adaptive immunity, as their presence leads to a more rapid and effective immune response to subsequent encounters with their antigen. + +Defects in B cell development and function can result in a variety of disease states. The generation of autoantibodies plays an important role in autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus. Mutations in genes important for B cell development contribute to primary immunodeficiencies such as X-linked agammaglobulinemia. The regular development of B cells includes stages which are prone to progression to malignancies such as leukemias and lymphomas." DOI:10.1038/nri3795|DOI:10.1182/blood-2008-02-078071|DOI:10.1007/978-981-15-3532-1_6|DOI:10.3389/fimmu.2019.02768 +553 CL:0000985 CL_0000985 "IgG plasma cells are a subtype of B cells that produces large amounts of high-affinity antibody during an adaptive immune response. These cells can be generated in extrafollicular sites or they can derive from mature follicular B cells that become activated by antigen. Activation induces somatic hypermutation resulting in affinity maturation, and class-switch recombination results in the production of immunoglobulin G (IgG) antibodies by these cells, culminating in the generation of highly specific IgG plasma cells. + +IgG antibodies are the most abundant form of antibodies in the body and are especially important in the secondary immune response involving memory B cells. IgG is typically found in monomeric form in the serum and it can be further subclassified as IgG1, IgG2, IgG3, and IgG4. IgG functions as an opsonin, triggering phagocytosis or antibody-dependent cell-mediated cytotoxicity of pathogens, and it can also trigger the classical complement cascade to enhance pathogen clearance. Additionally, IgG is the only antibody capable of crossing the placenta, thus providing passive immunity to the fetus during pregnancy and to the newborn for the first several months after birth." DOI:10.1016/j.it.2019.01.012|DOI:10.1016/C2009-0-62217-0|https://www.ncbi.nlm.nih.gov/books/NBK513460/ +554 CL:0000980 CL_0000980 "Plasmablasts are a subset of B cells, which are a crucial component of the adaptive immune system. Plasmablasts develop from mature B cells which have encountered antigen and are in the process of being activated. These B cell blasts may differentiate into short-lived plasmablasts, which can continue to divide and to secrete low-affinity antibodies, allowing for a rapid response to antigens. These cells may further differentiate into plasma cells which secrete large amounts of high-affinity antibodies. + +In response to antigens, follicular T cells deliver antigen-dependent signals to cognate mature B cells. This leads to the activation of the cognate B cells and their development into B cell blasts which can undergo class switch recombination. These cells migrate to extrafollicular sites and differentiate into plasmablasts which secrete antibodies which tend to exhibit low or moderate affinity for the antigen as the cells have not yet undergone somatic hypermutation. Some of these cells may migrate into the bone marrow and differentiate into plasma cells. " DOI:10.1038/nri3795|DOI:10.1016/j.immuni.2020.11.006|DOI:10.1007/978-981-15-3532-1_1|DOI:10.1111/sji.12336|DOI:10.1038/nri2217 +555 CL:0000984 CL_0000984 "IgA plasmablasts are a subset of B cells, which are a crucial component of the adaptive immune system. Plasmablasts develop from mature B cells which have encountered antigen and are in the process of being activated. These B cell blasts may differentiate into short-lived plasmablasts, which can continue to divide and to secrete low-affinity antibodies, allowing for a rapid response to antigens. These cells may further differentiate into plasma cells in the bone marrow which secrete large amounts of high-affinity antibodies. + +In response to antigens, follicular T cells deliver antigen-dependent signals to cognate mature B cells. This leads to the activation of the cognate B cells and their development into B cell blasts which can undergo class switch recombination. These cells migrate to extrafollicular sites and differentiate into plasmablasts which secrete antibodies which tend to exhibit low or moderate affinity for the antigen as the cells have not yet undergone somatic hypermutation. Some plasmablasts may undergo class switch recombination to produce IgA antibodies. + +IgA immunoglobulins are most commonly secreted at the mucosal surfaces, forming a protective barrier to prevent pathogen adherence and invasion, neutralizing viruses and toxins, and potentially preventing their entry into the body. This function underscores the importance of IgA plasma cells in immunological defense, particularly in the context of respiratory and intestinal infections. IgA can also interact with the body's commensal microbiota, maintaining a balance and preventing these microorganisms from triggering an immune response." DOI:10.1038/nri3795|DOI:10.1016/j.immuni.2020.11.006|DOI:10.1007/978-981-15-3532-1_1|DOI:10.1111/sji.12336|DOI:10.1016/j.immuni.2020.11.006 +556 CL:0000987 CL_0000987 "IgA plasma cells are a subtype of plasma cells distinguished by their characteristic production of IgA class antibodies or immunoglobulins. Originating from activated B lymphocytes in the germinal center, these cells represent a crucial component of the body's humoral immune response. These cells generally reside in mucosal-associated lymphoid tissue and are an important component of mucosal immunity. + +IgA plasma cells reside primarily within the lamina propria of the mucosal linings, such as the gastrointestinal, respiratory, and genital tracts. Here, they generate IgA, a specific type of antibody that serves as the first line of defense against invading pathogens. Because IgA immunoglobulins are secreted at the mucosal surfaces, they form a protective barrier to prevent pathogen adherence and invasion, neutralizing viruses and toxins, and potentially preventing their entry into the body. This function underscores the importance of IgA plasma cells in immunological defense, particularly in the context of respiratory and intestinal infections. + +However, the role of IgA plasma cells extends beyond direct pathogen neutralization. The antibodies they release also interact with the body's commensal microbiota, maintaining a balance and preventing these microorganisms from triggering an immune response. This indicates the dual functional role that IgA plasma cells serve in not only neutralizing potential threats but also in preserving the body's beneficial microbiota. Their role in orchestrating this delicate balance makes IgA plasma cells an essential part of the immune system, with profound implications for understanding the body's overall health and susceptibility to diseases, particularly those related to mucosal infections and immune responses." DOI:10.3389/fimmu.2021.791095|DOI:10.1111/imr.12980|DOI:10.1136/gut.51.2.150|DOI:10.3389/fimmu.2023.1114348|DOI:10.4161/19490976.2014.969977 +557 CL:0000986 CL_0000986 "IgM plasma cells are a type of differentiated B cell that contribute to the humoral immune response by secreting immunoglobulin M (IgM). IgM is typically secreted in the early phase of an immune response, typically by short-lived IgM plasmablasts which can produce short-lived IgM plasma cells, but long-lived IgM plasma cells have also been reported and appear to be important in the response to viral infections. + +IgM plasma cells have not undergone class switching. While they may produce lower-affinity antibodies earlier in the immune response, the pentameric structure of IgM antibodies grants these antibodies high avidity to their antigens. These antibodies can therefore neutralize pathogens and can also trigger the complement cascade to further contribute to the clearance of pathogens. + +IgM plasma cells also play an important role in mucosal immunity in addition to IgA plasma cells. Some subsets of IgM plasma cells may also function as regulatory cells and produce cytokines such as IL-10 and IL-35. " DOI:10.3389/fimmu.2020.595535|DOI:10.3389/fimmu.2020.01943|DOI:10.1016/j.it.2019.01.012|DOI:10.1016/j.coph.2015.04.006 +558 CL:0001042 CL_0001042 "T-helper 22 (Th22) cells, a subtype of CD4+ T cells, are part of the immune system and play distinct roles in the immune response. Named after its characteristic cytokine IL-22, the discovery of Th22 cells has brought major advancement in our understanding of T cell-driven inflammation. These cells significantly contribute to host defense and tissue repair, particularly in the skin, but may also be implicated in several inflammatory and autoimmune diseases. + +T-helper 22 cells are involved in immune defense against extracellular pathogens. They originate from naïve CD4+ T cells in the peripheral blood when stimulated by the cytokines IL-6 and TNF-alpha in the presence of IL-23. Following differentiation, Th22 cells are capable of migrating to tissues to produce and secrete IL-22. The cytokine IL-22, pivotal to the function of Th22 cells, acts on epithelial cells and fibroblasts to induce antimicrobial peptides and mediators of tissue repair. This contributes to the role of Th22 cells in maintaining the integrity of epithelial barriers, particularly in the epidermis of the skin and mucosa. + +However, these cells can become detrimental when their activity becomes dysregulated. Persistent activity of Th22 cells may lead to chronic inflammation and hyperproliferative disorders. These cells have been implicated in several diseases such as psoriasis, atopic dermatitis, rheumatoid arthritis, Crohn's disease, and systemic lupus erythematosus, suggesting the complex and dual role of Th22 cells in health and disease. " DOI:10.3389/fmed.2021.708140|DOI:10.1016/j.immuni.2012.08.024|DOI:10.1016/j.cyto.2021.155749|DOI:10.1172/JCI40202|DOI:10.3389/fimmu.2021.688066 +559 CL:0001054 CL_0001054 "CD14-positive monocytes includes all three subsets of human monocytes: CD14-positive, CD16-negative classical monocytes; CD14-positive, CD16-positive intermediate monocytes; and CD14-low, CD16-positive non-classical monocytes. Emerging from the bone marrow and entering the bloodstream, these monocytes play central roles in immune responses and regulation of inflammation. + +The primary function of the classical monocytes is to serve in the frontline of host defense against infections. They are primed to migrate to sites of infection, and they express pattern recognition receptors that help them identify and phagocytose pathogens, leading to their destruction. Classical monocytes also contribute to inflammation by producing several pro-inflammatory cytokines. In response to specific signals from tissues under pathological conditions, such as infection or injury, classical monocytes can leave the bloodstream and migrate towards the affected sites. Following their arrival, these cells differentiate into diverse cell types including macrophages and dendritic cells to combat specific pathogens or injury. + +Meanwhile, intermediate monocytes exhibit a combined functionality of classical and nonclassical monocytes in terms of their phenotypic characteristics, functional capabilities and gene expression profiles. They express high levels of CD14 (like classical monocytes) and also express CD16 (like non-classical monocytes). These monocytes generally release lower amounts of cytokines compared to classical and non-classical monocytes, but produce the most reactive oxygen species. Intermediate monocytes may also induce T cell proliferation and express high levels of major histocompatibility complex molecules for antigen presentation. Intermediate monocytes also appear to play a role in inflammatory conditions, although their functions are less clear. + +Finally, non-classical monocytes patrol the endothelium and, upon sensing inflammation or injury, migrate across it. Non-classical monocytes are also involved in the removal of damaged cells via phagocytosis. This process enables the cells to engulf and destroy pathogens, debris, and apoptotic cells. During homeostasis, these monocytes appear to have an important function in maintaining vascular integrity." DOI:10.1111/sji.12883|DOI:10.3389/fimmu.2015.00423|DOI:10.1182/blood-2009-07-235028|DOI:10.3389/fimmu.2019.02035|DOI:10.1038/nri.2017.28 +560 CL:0001043 CL_0001043 "Activated CD4-positive, alpha-beta T cells are part of the adaptive immune system in humans, playing a critical role in fighting against infections and diseases. These cells carry CD4 surface proteins and are activated when they encounter an antigen presented by an antigen-presenting cell (APC). The CD4-positive category of T cells is further described as “helper” cells because they assist with numerous immune responses, making them vital players in the human immune system. + +Upon activation, these CD4-positive, alpha-beta T cells can differentiate into several subtypes, each with its own specialized function. These subtypes include Th1 cells that are involved in cellular immunity against intracellular pathogens, Th2 cells that coordinate humoral immunity and the response to extracellular parasites, and Th17 cells that play a role in protecting against fungal and bacterial infections. Activated CD4-positive T cells also have the ability to develop into follicular helper T (Tfh) cells crucial for helping B cells produce antibodies, and regulatory T (Treg) cells, necessary for suppressing excessive immune reactions to self and non-self antigens to avoid tissue damage. Activated CD4-positive, alpha-beta T cells also help in the organization of the immune system's memory. They have a long lifespan and provide a quick and specific immune response in case the same antigen is encountered again, which forms the basis of lifelong immunity to many pathogens after initial exposure. " DOI:10.1038/s41590-023-01510-4|DOI:10.1155/2012/925135|DOI:10.3389/fimmu.2022.867189|DOI:10.1038/nri3152|DOI:10.1111/j.1365-3083.2009.02308.x +561 CL:0001049 CL_0001049 "The activated CD8-positive, alpha-beta T cells are specialized immune cells that are critical to the adaptive immune system. Characterized by the presence of CD8 receptors and alpha-beta T cell receptors on their surface, these cells are also known as cytotoxic T cells or CD8-positive T cells. They play a central role in inducing and managing immune responses, especially against viral and intracellular bacterial infections, and in tumor surveillance. + +Upon activation, these cells undergo rapid proliferation and differentiation, ultimately developing into effector T cells that are capable of identifying and neutralizing infected or cancerous cells. The activation usually occurs when their T-cell receptors recognize a specific antigens displayed on the surface of infected cells or tumor cells in the context of Major Histocompatibility Complex (MHC) Class I molecules. These cells also require co-stimulatory signals for full activation. Upon recognition of such antigens, CD8-positive T cells release perforin and granzymes. Perforin forms pores in the target cell membrane and granzymes enter through these pores to initiate apoptosis, or programmed cell death. + +Importantly, a subset of these activated CD8-positive T cells develops into memory T cells following a primary immune response. These memory cells persist in the body long-term and provide a quick and efficient immune response upon secondary exposure to the same antigen, therefore conferring immunological memory. Their long-lived nature and the ability to mount a more robust response upon reinfection are crucial characteristics of adaptive immunity." DOI:10.1016/j.immuni.2011.07.010|DOI:10.1038/s41416-020-01048-4|DOI:10.1038/s12276-023-01105-x +562 CL:0001044 CL_0001044 "Effector CD4-positive, alpha-beta T cells, often referred to as CD4+ T cells, are subtypes of T lymphocytes that play a central role in cell-mediated immunity. They are characterized by the surface expression of the CD4 glycoprotein and by the expression of the T-cell receptor that includes alpha and beta chains. CD4+ T cells are essential in activating and directing other immune cells to execute targeted and effective responses against pathogens and malignant cells. + +Their primary function is to help augment the immune response. Upon binding to a specific antigen through their T-cell receptor, CD4+ T cells stimulate B cells to produce antibodies and promote maturation of cytotoxic T cells. In addition, they also induce macrophages and other immune cells to destroy any intruding microbes. These cells play an indispensable role in controlling and orchestrating the immune responses by producing a broad range of signaling compounds, called cytokines, which can tune the activity of many other immune cells. + +These CD4+ T cells differentiate into several subsets like Th1, Th2, Th17, and T regulatory cells after activation, characterized by characteristic cytokine profiles and specific effector functions. For example, Th1 cells are instrumental against intracellular bacterial or viral infections, Th2 cells combat parasitic infections, and Th17 cells protect against fungal infections. In contrast, T regulatory cells (Tregs) also derive from CD4+ T cells and maintain immune homeostasis by preventing overactive or autoimmune responses. " DOI:10.1155/2012/925135|DOI:10.1016/j.it.2021.06.003|DOI:10.1146/annurev-immunol-030409-101212|DOI:10.3389/fimmu.2022.973813 +563 CL:0001056 CL_0001056 "Human dendritic cells, named for their tree-like extensions called dendrites, are a type of immune cell that form a critical bridge between the innate and adaptive immune systems. They are derived from hematopoietic bone marrow progenitor cells and can be found throughout the body poised as sentinels in locations such as the skin, lungs, or liver, as well as immune organs such as the thymus, lymph nodes, or spleen. They can also be found in an immature state in the blood. Dendritic cells serve as antigen-presenting cells, with a primary function of processing and presenting antigens to T-cells to facilitate an immune response. + +Upon encountering an antigen, dendritic cells engulf the pathogen via phagocytosis and subsequently process the pathogen into antigens. These antigens are then presented on the surface of the dendritic cell in the context of major histocompatibility complex (MHC) molecules. The dendritic cell migrates to the lymph nodes, containing naive T-cells, and presents the antigens to them. This process triggers the activation of cognate T-cells into effector T-cells, which can then recognize and eradicate cells bearing the same antigen. + +Additionally, the dendritic cells can influence the type of immune response the body will mount. They communicate with T-cells through the use of co-stimulatory molecules and cytokines. Depending on the type of co-stimulatory molecules used and the set of cytokines released, dendritic cells can promote the development of a cellular immune response, dominated by cytotoxic T cells effective against intracellular pathogens such as viruses, a humoral response, mediated by B cells and effective against extracellular bacteria and toxins, or a tolerogenic response. Thus, dendritic cells play a pivotal role in human immunity, helping the body to effectively combat infections, prevent autoimmune diseases, and maintain tolerance to healthy self-tissues." DOI:10.1016/bs.ircmb.2019.07.004|DOI:10.1111/imm.12888|DOI:10.1146/annurev-immunol-061020-053707|DOI:10.1038/nri.2016.116 +564 CL:0001058 CL_0001058 "Human plasmacytoid dendritic cells (pDCs), initially known as interferon-producing cells, are a unique subpopulation of dendritic cells. Unlike conventional dendritic cells (cDCs), plasmacytoid dendritic cells are characterized by their distinctive plasma cell-like morphology. These cells play vital roles in the innate and adaptive immune response, particularly in the antiviral response. Highly prevalent in the blood and lymphoid organs, pDCs are rare in non-lymphoid tissues, with the exception of inflamed tissues and tumors where they are often recruited. + +A key role of plasmacytoid dendritic cells is their rapid and robust production of type 1 interferons in response to viral infections. This is crucial for antiviral defense as interferon signals to other immune cells to increase their antiviral defenses. pDCs achieve this by detecting viral nucleic acids in the cytosol through Toll-like receptors (TLRs), specifically TLR7 and TLR9. Upon recognition, these cells quickly produce substantial amounts of interferons, which plays a significant role in the containment of viral replication and the development of acquired antiviral immunity. + +The potential of plasmacytoid dendritic cells for antigen presentations to naive T cells is relatively low under steady-state conditions. Upon activation by certain stimuli, such as viruses or CpG oligodeoxynucleotides, they have the ability to differentiate into efficient antigen-presenting cells. This transition to activated cells involves an upregulation of major histocompatibility complex (MHC) class II molecules and co-stimulatory molecules, thus allowing them to effectively present antigenic peptides to naive T cells. This crucial function in linking innate and adaptive immunity underlines the importance of pDCs to the human immune response." DOI:10.1016/j.immuni.2018.12.027|DOI:10.1038/nri3865|DOI:10.1016/j.immuni.2007.06.006|DOI:10.1016/bs.ircmb.2019.07.004|DOI:10.1002/cti2.1139 +565 CL:0001057 CL_0001057 "Human myeloid dendritic cells are a subset of dendritic cells derived from the common myeloid progenitor cell. ""Conventional"" and ""myeloid"" DCs are often used interchangeably. In contrast, dendritic cells may also arise from the common lymphoid progenitor. Monocyte-derived dendritic cells may also be induced by inflammatory states. + +Dendritic cells function as antigen-presenting cells and are able to activate naïve T cells to induce the adaptive immune response. Dendritic cells capture, process, and present antigens derived from pathogens to mount a specific immune response against the invading antigen. Dendritic cells also produce a range of cytokines that help in modulating and recruiting other immune cells during an immune response. + +Dendritic cells can contribute to immune tolerance by deleting self-reactive T cells or by inducing regulatory T-cells, thereby preventing autoimmunity. Dendritic cells thus are important in orchestrating the human adaptive immune response and are pivotal in combating infections and maintaining tolerance to self." DOI:10.1016/j.imbio.2014.12.010|DOI:10.1016/j.immuni.2007.06.006|DOI:10.1111/imm.12888|DOI:10.1002/jlb.66.2.205|DOI:10.3389/fimmu.2018.03176 +566 CL:0001065 CL_0001065 "Innate Lymphoid Cells (ILCs) are a class of immune cells that are vital to innate immunity, which is the body's first line of defense against pathogens. These cells, unlike T and B cells, do not express diverse antigen receptors. However, they have a remarkable ability to rapidly respond to pathogens because they do not require clonal expansion after stimulation. Originating from common lymphoid progenitor cells in the bone marrow, ILCs are primarily located in barrier tissues such as the skin, lung, and gut where they play substantial roles in tissue homeostasis, inflammation, and immune response. + +ILCs have been widely classified into three different groups based on their cytokine production and transcription factor expression, paralleling the T-helper (Th) cell classification. Group 1 ILCs (including natural killer (NK) cells and ILC1) produce interferon-gamma and transiently express T-bet. They are involved in immune responses against intracellular bacteria and parasites. Group 2 ILCs (ILC2) produce Th2-type cytokines like interleukin (IL) -5 and -13, and are involved in protection against helminth parasites and in triggering allergic inflammation. Lastly, Group 3 ILCs (ILC3) produce IL-22 and IL-17, which contribute to the defense against extracellular bacteria and fungi, and are critical for lymphoid tissue formation. More recently, NK cells and ILC1 cells have been split into their own classes, and lymphoid tissue-inducer (LTi) cells have been added. LTi cells support secondary lymphoid organ development during fetal development. + +Specific types of ILCs are integral in different biological processes. For instance, NK cells are key players in the anti-viral and anti-tumor responses, while ILC2s assist in maintaining metabolic homeostasis by controlling adipose tissue inflammation and beiging. Importantly, dysregulation in ILC functions have implications on various pathologies including chronic inflammation, autoimmune diseases, and cancers. Therefore, understanding the biology of ILCs provides crucial insights for developing therapeutic strategies against such afflictions." DOI:10.1038/nri.2017.86|DOI:10.1002/eji.201747294|DOI:10.1016/j.cell.2018.07.017|DOI:10.1101/cshperspect.a030304|DOI:10.3389/fimmu.2022.1040624 +567 CL:0001062 CL_0001062 "The ""effector memory CD8-positive, alpha-beta T cell, terminally differentiated"" is a highly specialized type of T lymphocyte that plays an essential role in the human body's immune response. These cells, abbreviated as TEMRA CD8+ T cells, belong to the greater T cell family, derived from the lymphoid lineage of cells. Uniquely characterized by the CD8 surface marker, they represent a subset of the heterogeneous T cell population. TEMRA CD8+ T cells have gained attention in the immunology field due to their significant role in mediating cellular immune responses against viral and bacterial infections, as well as possessing potential implications in autoimmune disorders and immunotherapy. + +The fundamental function these cells lies in their capacity to rapidly respond to pathogenic invasions effectively. Upon re-encountering an antigen previously met, they are capable of immediate effector function, producing cytotoxic granules and pro-inflammatory cytokines. One of their key roles is to directly kill infected cells and secrete inflammatory mediators like IFN-γ and TNF-α. This ability to immediately respond to previously encountered antigens distinguishes them from naive T cells, which lack effector function and require differentiation upon first antigen encounter. + +""Terminal differentiation"" in TEMRA CD8+ T cells refers to the state where they have reached the end of their differentiation pathway, and they are described as fully mature. They express several cell surface markers such as CD45RA, which play a crucial role in their homing capacity. These cells have a limited proliferative capacity compared to the less differentiated subsets. +" DOI:10.1016/j.immuni.2018.01.007|DOI:10.1016/j.ebiom.2023.104520|DOI:10.1186/s13073-021-00918-7|DOI:10.1101/cshperspect.a037929 +568 CL:0001081 CL_0001081 "Human group 2 innate lymphoid cells, also known as ILC2 cells, are a subset of the innate lymphoid cell family - a family of immune cells crucial for host defense, immune regulation, and tissue repair especially in the context of infections and inflammatory conditions. These cells are largely tissue-resident, predominantly residing in barrier tissues such as the skin, lungs, and gastrointestinal tract. ILC2s are defined by their expression and reliance on the GATA3 transcription factor. In humans, these cells express CD25, CD127, CD161, and CRTH2. + +ILC2 cells play a significant role in the immune response, especially against parasitic infections and in allergic responses and autoimmune disorders. They predominantly produce type 2 cytokines including interleukin-5 (IL-5) and interleukin-13 (IL-13) in response to stimuli such as cytokines IL-25 and IL-33, which are often produced by epithelial cells in response to tissue damage. IL-5 is crucial for eosinophil activation, a component of the immune system that plays a key role in combating parasitic infections. Concurrently, IL-13 helps in expelling parasites from the body's system, as well as enforcing barrier integrity. + +ILC2s are also instrumental in tissue repair and homeostasis. They help in maintaining body metabolism and fat storage, largely by producing a hormone known as methionine-enkephalin peptides. ILC2 cells also aid in early tissue repair processes, by the secretion of amphiregulin, a growth factor. Despite their protective functions, ILC2 cells can also contribute to pathologies such as asthma and other inflammatory diseases if their actions are not properly regulated." DOI:10.1101/cshperspect.a030304|DOI:10.1038/nature14189|DOI:10.1016/j.cell.2018.07.017|DOI:10.1002/eji.201747294|DOI:10.1038/nri.2017.86 +569 CL:0001201 CL_0001201 "The CD19-positive B cell, often simply known as the B cell, is an integral component of the body's immune system that plays a pivotal role in humoral immunity. These cells are ubiquitous in the lymphoid organs such as the spleen and lymph nodes, and are also found circulating in the blood. CD19 is a co-receptor that belongs to the immunoglobulin superfamily, and its presence is a marker of B cells from the time they are progenitor cells in the bone marrow through their maturation and differentiation into plasma cells. + +The primary function of CD19-positive B cells revolves around their activation and production of high-affinity antibodies against antigens. B cells first encounter antigens, which bind to the B cell receptor (BCR) on the cell surface. This antigen intracellularly signals the B cell to become active. CD19 plays a key role in this activation, by lowering the threshold of the BCR-mediated signals and thus enhancing the sensitive response of B cells to the antigens. + +Furthermore, activated B cells undergo a series of processes to carry out their defensive roles effectively. They proliferate rapidly forming a clone of identical cells and then differentiate into memory B cells or antibody-producing plasma cells. Memory B cells persist in the body and provide long-term immunity by responding faster and more vigorously upon subsequent encounters with the same antigen. Plasma cells produce large quantities of antibodies, which can bind the specific antigen and aid in its neutralization or destruction." DOI:10.1186/2162-3619-1-36|DOI:10.1016/B978-0-12-397933-9.00007-2|DOI:10.1007/978-981-15-3532-1_1 +570 CL:0002009 CL_0002009 "Macrophage dendritic cell progenitors (MDPs), sometimes referred to as monocyte dendritic cell progenitors, are a group of bone marrow hematopoietic progenitor cells that are committed to both the monocyte/macrophage and dendritic cell lineages. MDPs represent a vital link of innate and adaptive immunity by producing these important immune cells. + +Macrophage dendritic cell progenitors develop from granulocyte, monocyte, and dendritic cell precursors (GMDPs). At the stage of MDPs, they lose the ability to differentiate into granulocytes and retain the ability to differentiate into monocytes and a common dendritic cell precursor (CDP). + +Macrophage dendritic cell progenitors' primary function is the differentiation into either monocytes/macrophages and dendritic cells. Monocytes/macrophages are phagocytic cells involved in detecting, engulfing, and destroying pathogens and apoptotic cells, thereby maintaining homeostasis. Dendritic cells are antigen-presenting cells that process antigen and present it on their surface to the T-cells of the immune system. This process activates the body's adaptive immune response to specific antigens. " DOI:10.1111/imm.12888|DOI:10.1016/bs.ircmb.2019.07.004|DOI:10.1038/s41577-020-00413-x|DOI:10.1038/nprot.2015.092|DOI:10.1128/microbiolspec.mchd-0015-2015 +571 CL:0001203 CL_0001203 "The CD8-positive, alpha-beta memory T cell, CD45RO-positive are highly specialized cells that plays an integral role in the body's adaptive immune responses. Recognized by its marker proteins CD8, alpha-beta T-cell receptor (TCR), and CD45RO, this category of memory T cells holds responsibility for recognizing and eliminating previously encountered foreign elements, such as viral or bacterial pathogens. + +Upon re-exposure to pathogens, these cells are able to quickly evolve into cytotoxic T cells (CTLs), which are capable of killing the pathogen-infected host cells. This accelerated response feature underscores the 'memory' part of the nomenclature of this cell type. These memory T cells also produce specific cytokines such as interferon-gamma (IFN-γ), interleukin 2 (IL-2), and tumor necrosis factor (TNF), which are crucial for initiating cellular and inflammatory response against such threats. + +These cells are identified by the CD45RO marker, which denotes the “memory” phenotype. Structurally, the CD8-positive cell is distinguished by the expression of the CD8 co-receptor, which interacts with the major histocompatibility complex class I (MHC I) of the infected host cell. Predominantly, these cells use their alpha-beta T cell receptors to specifically recognize the antigenic peptides, thereby determining specificity in immune response. " DOI:10.4049/jimmunol.167.1.212|DOI:10.1007/s13238-020-00707-9|DOI:10.1016/j.imlet.2017.02.012 +572 CL:0002038 CL_0002038 "T follicular helper cells (also known as Tfh cells) are a specialized subgroup of T cells that provide pivotal assistance to B cells, which are integral components of the immune system. They are primarily located in the germinal centers of lymphoid organs such as the spleen and lymph nodes. These cells play a substantial function in the development of antigen-specific B cell immunity, which is critical for the human body's immune response. + +Tfh cells, once activated by interaction with dendritic cells, express the surface marker CXCR5 that assists in their migration to B cell areas in secondary lymphoid organs. Here, they specifically interact with B cells to induce class switching, affinity maturation, and differentiation of B cells into plasma cells and memory cells. This interaction primarily culminates into the production of high-affinity, class-switched antibodies, enhancing the body's adaptive immune response. + +Further, the unique production of IL-21 cytokine by Tfh cells enables them to support B cell differentiation and proliferation. However, the regulation of Tfh cell responses must be carefully maintained as dysregulation can lead to pathogenic responses including autoimmunity and chronic inflammation. Indeed, the upregulation of Tfh cells has been associated with multiple autoimmune diseases such as lupus and Sjogren's Syndrome. " DOI:10.1038/s41577-022-00693-5|DOI:10.1016/j.immuni.2019.04.011|DOI:10.1038/s41467-019-12446-5|DOI:10.1093/intimm/dxp112|DOI:10.1016/j.jaut.2022.102976 +573 CL:0002045 CL_0002045 "Pre-pro B cells, or Hardy fraction A, represent the earliest stage in the B-cell developmental lineage, residing at the pivotal point of differentiation from self-renewing hematopoietic stem cells into committed progenitors of B lymphocytes. These cells are found in the bone marrow, which serves as the primary site for B cell lymphopoiesis. + +Common lymphoid progenitors commit to the B cell lineage following upregulation of transcription factors such as PAX5 and EBF1. The resulting pre-pro B cells express CD45R (B220) but do not yet express CD19, which is upregulated at the next developmental stage, pro-B cells or fraction B. Additionally, pre-pro B cells still lack immunoglobulin rearrangements." DOI:10.1016/j.it.2022.01.003|DOI:10.1016/B978-0-12-397933-9.00007-2|DOI:10.1111/j.1600-065X.2000.imr017517.x|DOI:10.1007/978-981-15-3532-1_1|DOI:10.1016/j.it.2022.01.003 +574 CL:0002117 CL_0002117 "IgG-negative class switched memory B cells are a specialized subset of class switched memory B cells distinguished by their lack of IgG cell surface expression. They therefore generally refer to IgA-expressing memory B cells, as IgE-expressing memory B cells have not been definitively detected. As part of the adaptive immune system, they play a crucial role in maintaining the immune response to previously encountered pathogens. These cells are the products of class switching, a fundamental process in the immune system where B cells change the type of antibody they produce during their activation process. + +During the initial encounter with an antigen, mature B cells are activated and can undergo somatic hypermutation and class switch recombination in germinal center reactions, resulting in the ability to produce high-affinity antibodies. These cells can develop into antibody-producing plasma cells to respond to the antigen during the primary encounter, or they can develop into long-lived memory B cells which contribute to immunological memory. These cells respond during subsequent exposures to the same antigen. + +IgA memory B cells are the predominant memory B cell subset in mucosal tissues. Upon re-exposure to the antigen against which they were initially primed, they can rapidly differentiate into antibody-secreting cells to generate a robust respond to the antigen." DOI:10.3389/fimmu.2019.01787|DOI:10.1111/imr.13016|DOI:10.1038/nri3802|DOI:10.1038/leu.2016.226 +575 CL:0002397 CL_0002397 "Intermediate monocytes, also defined as CD14++CD16+ monocytes, constitute one of the three subsets of human monocytes which also include classical and non-classical monocytes. These cells play a crucial role in the physiological function of the immune system and are particularly significant in the human body's response to inflammation and infection. With a diverse array of functions, intermediate monocytes uniquely contribute to the immune response potency by bridging the gap between the classical and non-classical monocyte subsets. + +Intermediate monocytes exhibit a combined functionality of the two other subsets in terms of their phenotypic characteristics, functional capabilities and gene expression profiles. They express high levels of CD14 (like classical monocytes) and also express CD16 (like non-classical monocytes). These monocytes generally release lower amounts of cytokines compared to classical and non-classical monocytes, but produce the most reactive oxygen species. Intermediate monocytes may also induce T cell proliferation and express high levels of major histocompatibility complex molecules for antigen presentation. + +The relative number of intermediate monocytes in the bloodstream increases under conditions of severe inflammation and infection, although their roles have not yet been clearly defined. Additionally, some studies reported findings on monocytes with a combined population of intermediate and non-classical monocytes, further complicating the understanding of the function of these cells." DOI:10.2147/JIR.S292513|DOI:10.1182/blood-2010-02-258558|DOI:10.1182/blood-2010-12-326355 +576 CL:0002419 CL_0002419 "Mature T cells are highly specialized immune cells that plays a vital role in the body's lymphatic system. Mature T cells originate from hematopoietic progenitor cells found in the bone marrow. These cells then migrate to the thymus, an organ located in the chest, where they develop and mature into fully functional T cells. The T in T cells stands for thymus, reflecting the integral role this organ plays in T cell's maturation and development. There are several types of mature T cells, including Helper T cells (CD4+), Cytotoxic T cells (CD8+), and Memory T cells, all distinguished by their specific functions in the immune response. + +Mature T cells act as mediators, carrying information about pathogens and activating other immune cells to respond to these invaders. The CD4+ Helper T cells recognize antigens presented by Antigen Presenting Cells (APCs) and release cytokines to stimulate other immune cells, like B cells to produce antibodies or macrophages to phagocytose pathogens. On the other hand, Cytotoxic T cells (CD8+) directly intervene by identifying and killing target cells infected with viruses or other intracellular pathogens. Each T cell is highly specific, with the ability to recognize a single type of antigen. + +The function of mature T cells extends beyond pathogen defense. These cells also participate in the regulation of immune response. Memory T cells, a byproduct of an immune response, are specifically enabled to respond quickly if the same antigen reenters the body providing a rapid and efficient immune response. Regulator T cells, another subset of T cells, help maintain immune tolerance by suppressing overactive immune components and preventing autoimmunity. Thus, mature T cells play a vital role in balancing immunity, enabling the body to defend against pathogens while preventing self-destruction." DOI:10.1016/j.immuni.2018.01.007|DOI:10.1046/j.1365-2567.2002.01447.x|DOI:10.1016/j.immuni.2018.01.007|DOI:10.1038/s12276-023-01105-x|DOI:10.1155/2012/925135 +577 CL:0002425 CL_0002425 "The early T lineage precursor, also referred to as the double negative 1 (DN1) cell, is the first cell to arrive in the thymus from the bone marrow that will develop into cells of the T cell lineage. These cells are referred to as double negative due to their lack cell surface expression of CD4 and CD8. In mice, they express c-kit and CD44 but not CD25, while the human equivalent cells express CD34 and CD7 but not CD1a. These cells are not yet committed to the T cell lineage. + +Once the DN1 cell enters the thymus, it begins to respond to the Notch signaling environment and begins to activate genes related to T cell development and to proliferate. The markers used to define this stage differ between humans and mice. In humans, DN1 cells express CD34; in mice, the cells express c-kit and CD44. + +In mice, these cells can go on to the DN2-4 stages, to the double positive stage, then to the single positive stage, thereby producing αβ T cells such as CD4+ cells, CD8+ cells, regulatory T cells, or invariant natural killer T cells; throughout the developmental process, they may also branch off to form γδ T cells instead." DOI:10.1016/bs.ai.2015.09.002|DOI:10.1016/B978-0-7020-6896-6.00008-9|DOI:10.1016/B978-012088451-3.50015-6|DOI:10.1016/j.smim.2022.101662 +578 CL:0002420 CL_0002420 "Immature T cells, also known as thymocytes, are progenitor cells that originate in the bone marrow and undergo a developmental process in the thymus. They undergo a series of complex and critical maturation events in the thymus before they are released into the blood as mature, functional T cells. These immature T cells represent a spectrum of cells in various stages of maturation, eventually giving rise to the mature T cell compartment with a diverse T cell receptor repertoire that is able to respond to a wide range of antigens. + +Immature T cells participate in thymopoiesis, resulting in the generation of mature T cells. This process involves the selection of T cells according to their ability to recognize and bind to an array of specific antigens without causing harm to the body's own cells. They undergo both positive and negative selection processes. During positive selection, cells capable of binding to major histocompatibility complex (MHC) molecules are selected, while the remaining cells die by apoptosis. During negative selection, cells that bind too strongly to the body's own antigens are eliminated. Both of these processes ensure that the body produces a diverse range of T cells that can fight infections without harming the body. + +In terms of cell surface markers, immature T cells display a changing profile during maturation, starting as double negative cells (expressing neither CD4 nor CD8 markers) then becoming double positive cells (expressing both CD4 and CD8). The final stage of maturation involves commitment to either the CD4+ helper T cell lineage or the CD8+ cytotoxic T cell lineage. Each of these pathways emphasizes the central role of immature T cells in ensuring the versatility and adaptability of the immune system, capable of responding to a vast array of pathogenic threats while preventing autoimmune disease." https://www.ncbi.nlm.nih.gov/books/NBK27123/|DOI:10.1038/nri3667|DOI:10.1016/B978-0-12-374279-7.04011-X|DOI:10.3389/fimmu.2022.885280|DOI:10.3389/fimmu.2023.1197066 +579 CL:0002457 CL_0002457 "Epidermal Langerhans cells are immune cells found in the epidermis. Initially thought to be dendritic cells, they are now considered to be specialized tissue-resident macrophages. They originate from embryonic yolk sac macrophages and fetal liver monocytes, are self-renewing, but may also be replaced by other bone-marrow derived cells during inflammation. + +Langerhans cells possess both macrophage- and dendritic cell-like properties and functions. They can self-maintain locally, survey antigens in the epidermis, migrate to lymph nodes, and can present antigens to T cells. Langerhans cells therefore play an important role in the activation of proinflammatory adaptive immune responses in the skin and are critical in the response to pathogens and cancer. + +Langerhans cells are also important suppressors of the adaptive immune responses in the skin, contributing to immune tolerance and preventing excessive or unnecessary immune responses. They are capable of recognizing self-antigens and communicating the information to T cells, thereby generating tolerance and preventing autoimmune reactions. Furthermore, they play an important role in skin conditions such as psoriasis and skin cancers, frequently becoming the subject of research for treatments." DOI:10.1097/MOH.0000000000000202|DOI:10.1016/j.it.2017.06.008|DOI:10.3389/fimmu.2017.01941|DOI:10.1016/B978-0-323-31696-5.00009-7|DOI:10.3389/fimmu.2018.01768 +580 CL:0002489 CL_0002489 "The double negative thymocyte is the first stage of thymocyte development in the thymus to produce mature T cells. They are referred to as ""double negative"" due to their lack of cell surface expression of both CD4 and CD8 co-receptors, two important T-cell markers. As part of their progression towards maturity, these thymocytes undergo a critical process known as T-cell receptor (TCR) rearrangement, ensuring the generation of functional T cells that can react to a wide range of pathogens. + +In mice, the double negative stage can be further subdivided into stages 1-4. DN1, also referred to as early T cell precursors, enter the thymus and begin to express T cell programming and begin to proliferate, although the cells are not yet fully committed to the T cell lineage at this stage. The DN2 stage includes an initial phase of further proliferation (called the DN2a stage) followed by slowed proliferation (DN2b). At the DN3 stage, rearrangement of the TCR beta chain occurs. Signaling through a pre-TCR is a checkpoint that represents commitment to the alpha-beta T cell lineage and is referred to as beta-selection. This results in DN4 cells. From here, cells progress through the double positive (DP) stage and the single positive (SP) stage to develop mature CD4+ and CD8+ T cells. + +While less characterized in humans, the DN phase is characterized in two stages. Lineage commitment is associated with the the second phase in human T cell development. " DOI:10.1016/bs.ai.2015.09.002|DOI:10.1016/B978-0-7020-6896-6.00008-9|DOI:10.1016/bs.ctdb.2016.01.004 +581 CL:0002678 CL_0002678 "Memory regulatory T cells, also known as memory Treg cells, are a subpopulation of T cells, an integral part of the adaptive immune system. These specialized T cells are characterized both by having previously responded to antigen, as indicated by their “memory” designation, and have immune regulatory functions. Memory regulatory T cells are believed to play an important role in regulating the memory response. + +Defining these cells phenotypically is challenging, as there are not well-defined markers that distinguish memory regulatory T cells from regulatory T cells, especially in human cells. Epigenetic studies may aid in identifying regulatory T cells which have been previously activated. + +Memory regulatory T cells may serve as important mediators of long-lived tolerance to self-antigen. However, some memory regulatory T cells may instead recognize pathogen-derived antigens which are able to rapidly respond and proliferate in response to antigenic re-challenge. These memory regulatory T cells can suppress effector T cell function and proliferation, likely to regulate the memory response to prevent unnecessary host tissue damage." DOI:10.1038/nri.2015.1|DOI:10.3390/cells11101687|DOI:10.1038/s41590-023-01510-4 +582 CL:0002677 CL_0002677 "Naive regulatory T (Treg) cells are a subset of T cells, specifically of the CD4+ T cell population. T regulatory cells are pivotal in maintaining the immune system's balance by managing self-tolerance and controlling the extent of the immune response to minimize damage to host tissues. These cells are designated as naive as they have not yet encountered an antigen. T regulatory cells can be identified by expression of the surface protein CD4 and intracellular protein FoxP3, while naive T regulatory cells also express CD45RA, CCR7, and CD62L with low expression of CD127. + +Naive regulatory T cells are thought to develop in the thymus from thymocytes that possess high affinity for self-peptide, although they may also develop peripherally as well. Upon antigen exposure, naive regulatory T cells rapidly differentiate into effector Tregs and memory Tregs. This activation is coupled with expression of different cell surface markers and increased secretion of immune-suppressing cytokines like interleukin-10 (IL-10) and TGF-beta. + +Regulatory T cells possess suppressive activity and are important for the induction of tolerance to autoantigens, food allergens, commensal bacteria, and the developing fetus during pregnancy. They are important in maintaining peripheral tolerance and homeostasis and in preventing chronic inflammation. Regulatory T cells may interact with multiple cell types, such as other conventional T cells and antigen-presenting cells, to modulate the immune response. " DOI:10.3389/fimmu.2023.1321228|DOI:10.3389/fimmu.2019.03100|DOI:10.1146/annurev-immunol-042718-041717|DOI:10.18632/oncotarget.7512 +583 CL:0001019 CL_0001019 "The 'CD115-positive monocyte OR common dendritic progenitor' includes two groups of myeolid cells that are already committed to a monocyte or dendritic phenotype, respectively. CD115-positive monocytes and common dendritic progenitors (CDPs) share a common precursor, the macrophage dendritic cell progenitor (MDP), which has lost the ability to differentiate into granulocytes while retaining the ability to differentiate into monocytes and CDPs. + +CDPs then primarily differentiate into two main types of dendritic cells: conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs). This diversification enhances the functional variety of the immune response. cDCs excel at capturing, processing, and presenting antigens to both naive and memory T-cells, guiding the adaptive immune response. Conversely, pDCs are potent cytokine producers, particularly interferons, vital for antiviral responses. + +" DOI:10.1146/annurev-immunol-020711-074950|DOI:10.3389/fimmu.2019.01222|DOI:10.3390/ijms23094885|DOI:10.1038/s41577-020-00413-x|DOI:10.3389/fimmu.2014.00423 +584 CL:0000123 CL_0000123 Neuron associated cells (sensu Vertebrata), often known as glial cells or neuroglia, play a vital role in maintaining the proper functioning of the vertebrate nervous system. These cells, which outnumber the neurons they support, are intimately involved in all aspects of neuronal homeostasis and function. They provide both structural and nutritional support, regulate the neuronal microenvironment, and modulate signal transmission. Unlike neurons, neuron associated cells do not transmit nerve impulses but assist in the transmission process directly and indirectly by maintaining the necessary conditions for it. Neuron associated cells are integral to the elaborate and dynamic processes that underlie vertebrate life. DOI:10.1038/nrn2720|DOI:10.1007/978-981-13-9913-8_2|DOI:10.1002/glia.21149 +585 CL:0002094 CL_0002094 "Interstitial cells of the ovary are a vital component of the ovarian tissue. They reside within the ovarian cortex, dispersed among the connective tissue surrounding the ovarian follicles. Despite not being directly associated with the follicles themselves, interstitial cells play a significant role in ovarian function, hormone production, and follicle viability. + +These cells are primarily responsible for the synthesis and secretion of androgens. Androgens are a class of hormones that are crucial for various physiological processes, including the development of secondary sexual characteristics, regulation of the menstrual cycle, and support of reproductive function. In addition to their role in androgen production, interstitial cells also contribute to the overall hormonal milieu within the ovary. They interact with other cell types, such as theca cells and granulosa cells, to coordinate hormone production and follicular development. This intricate interplay of different cell types is essential for the proper functioning of the ovary and the regulation of ovarian cycles. + +Furthermore, interstitial cells are subject to hormonal regulation themselves. Various hormones, such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) released by the pituitary gland, influence the activity of interstitial cells and modulate androgen production accordingly. This hormonal regulation ensures the finely tuned balance necessary for reproductive processes. + + +" DOI:10.1038/nrn2720|DOI:10.1023/A:1012700802220|DOI:10.1186/1477-7827-9-159 +586 CL:0002494 CL_0002494 "Cardiocytes are specialized cells that form the cardiac muscle tissues and play an essential role in maintaining heart function. These cells facilitate the heart's primary function - pumping blood throughout the body. Cardiocytes are distinctive for their striated appearance under the microscope due to the presence of a large number of contractile proteins and are interconnected by intercalated disks that allow electrical and mechanical connectivity. + +The primary function of cardiocytes is to manage the contraction and relaxation of the heart, which occurs in response to electrical impulses. This vital process allows the heart to maintain its rhythm and blood flow throughout the body. The electrical impulse begins in the cardiocytes of the sinoatrial node, then spreads through the heart, causing coordinated contraction and relaxation. These cells also respond to changes in bodily demands by fluctuating the rate and strength of their contractions. For example, during physical exertion, stress, or illnesses, the heart rate may increase to pump more blood and thus supply more oxygen and nutrients to the body's tissues. + +In addition to their role in conducting heartbeats, cardiocytes also participate in regulating blood pressure, ensuring oxygen supply meets the requirements of other body tissues, and maintaining ion homeostasis in the cardiovascular system. Furthermore, certain cardiocytes secrete atrial natriuretic peptide, a hormone that contributes to salt-water balance and blood pressure control. Unfortunately, cardiocytes have a significantly limited capacity to regenerate, making heart injuries particularly challenging to recover from. " DOI:10.1016/S0022-5223(99)70233-3|DOI:10.1038/s41586-020-2797-4|DOI:10.1016/j.gene.2015.06.029 +587 CL:1000500 CL_1000500 "Kidney interstitial cells, also referred to as renal interstitial cells, play a critical role in the structure and function of the kidneys. They are found in the interstitial space within the kidney and compose a diverse group of cells, including fibroblasts, pericytes, and immune cells such as lymphocytes and macrophages. Unlike other cell types in the kidney, interstitial cells are not involved in the direct process of filtration, reabsorption, or secretion of substances into and out of the blood. Instead, they are functionally and structurally supportive, aiding the nephrons, the functional units of the kidneys, to effectively carry out their roles. + +Kidney interstitial cells maintain the structural integrity of the kidney. They produce extracellular matrix proteins that provide a supportive scaffold to other cell types in the kidney. These proteins not only hold the kidney together but also play a crucial role in tissue repair following injury. Additionally, they contribute to the regulation of renal blood flow by interacting with the renal microvasculature, potentially influencing the process of urine formation indirectly. Another key role of kidney interstitial cells revolves around immune responses and inflammation. Through their interaction with immune cells, they can initiate and modulate inflammatory responses, thus playing a crucial role in defending the kidneys against infections. " DOI:10.2215/CJN.00640114|DOI:10.1159/000496278|https://www.kidney-international.org/article/S0085-2538(15)57139-1/pdf|DOI:10.1007/BF00186688|https://www.kidney-international.org/article/S0085-2538(15)57150-0/pdf +588 CL:1000494 CL_1000494 "Nephron tubule epithelial cells are vital components of the nephron, the basic structural and functional unit of the kidney. These cells play a pivotal role in the filtration, reabsorption, secretory and regulatory processes that maintain homeostasis in the body. Nephron tubules include a sequential arrangement of various segments, namely, the proximal convoluted tubule, the proximal straight tubule, the thin limb of Henle's loop, the distal convoluted tubule, and the collecting ducts – each comprised of unique epithelial cells to carry out their distinct functions. + +Epithelial cells in the proximal tubule, characterised by abundant mitochondria and microvilli, carry out reabsorption of essential nutrients, electrolytes and water, in addition to serving as a site for waste product secretion into filtrate. Further along, in the Loop of Henle, these cells participate in the counter-current multiplier system, critical for water reabsorption and concentration of the urine. The distal tubule and collecting duct epithelial cells have hormone receptors on their surfaces which respond to the body's need for water and electrolyte balance - main regulators being the hormones renin, angiotensin, aldosterone, and antidiuretic hormone (ADH). Based on the body's requirements, these cells can variably reabsorb water and specific solutes into the blood, or expel them into the forming urine." DOI:10.1146/annurev-physiol-052521-121841|DOI:10.2215/CJN.10391012|DOI:10.1002/cphy.c110019|DOI:10.1681/ASN.2018101025|DOI:10.4103/2230-8210.93729 +589 CL:1000617 CL_1000617 "Kidney inner medulla cells are specialized cells found within the inner medullary region of the kidney, an area responsible for the concentration and dilution of urine. These cells have a central role in maintaining the body's water and salt balance, as they participate in the reabsorption of electrolytes, water, and other solutes from the filtrate into the bloodstream. They orchestrate the final steps of urine formation before it leaves the kidney and enters the bladder. The cellular architecture in this region is heterogeneous and is composed of different subtypes, including interstitial cells, epithelial cells of the loop of Henle and collecting ducts, and vascular endothelial cells, with each subtype performing a specific role. + +Epithelial cells that line the loop of Henle and collecting ducts ensure the uptake of water and solutes. The loop of Henle, in particular, engages in a countercurrent multiplication process, generating a gradient of solute concentration in the medullary interstitium, which allows these cells to absorb more water from the filtrate. Interstitial cells in the inner medulla are thought to play a role in mediating renal inflammation and fibrosis, immune response, and tissue repair. Vascular endothelial cells help maintain blood flow through tiny vessels, supplying the cells with oxygen and nutrients for their function. +" DOI:10.4161/org.19308|DOI:10.1152/ajprenal.00236.2015|DOI:10.2215/CJN.08750812|DOI:10.1016/j.semnephrol.2015.01.010 +590 CL:1000746 CL_1000746 "Glomerular cells are key components of the renal system and are primarily located within the kidneys. These cells play a crucial role in the body’s ability to filter blood, remove waste products, and control electrolyte balance. The glomerular cells aggregate to form a structure known as the glomerulus, a small filtering unit part of the nephron, playing a critical role in the renal filtration system. + +Glomerular cells can be differentiated into three main types: podocytes, mesangial cells, and endothelial cells, each with distinct functions. Podocytes are a type of epithelial cells that form a layer around the glomerular capillaries. With their distinctive foot-like processes, they regulate the filtration process, allowing only certain substances to pass through while blocking the movement of larger entities like proteins, preventing them from entering the urine. Mesangial cells have both contractile and phagocytic features similar to smooth muscle cells and macrophages, respectively. These cells regulate blood flow within the glomerular capillaries and clear any debris that may accumulate in the basement membrane. Lastly, endothelial cells line the inner surface of the capillaries, working with podocytes to allow the passage of water, ions, and small molecules. +" DOI:10.3389/fmed.2021.740527|DOI:10.1146/annurev-physiol-052521-121841|DOI:10.3389/fendo.2014.00160|DOI:10.1038/s41581-021-00474-8|DOI:10.1016/j.biocel.2010.05.015 +591 CL:1000854 CL_1000854 "Kidney blood vessel cells, also known as renal vascular cells, are crucial constituents of the kidneys, which plays a cardinal role in vital physiological processes such as the regulation of blood pressure, blood filtration, and maintaining electrolyte balance. The cellular makeup of the renal vasculature encompasses endothelial cells, vascular smooth muscle cells, renin-secreting cells, pericytes, fibroblasts, mesangial cells, and the nerve fibers that provide innervation to the vessels. These cells are constituents of the intricate network of blood vessels navigating through the renal system. + +The primary function of kidney blood vessel cells is to facilitate the filtration of blood and the subsequent formation of urine. These cells form the inner lining of blood vessels known as endothelial cells, and their characteristics and functions vary slightly depending on their localization. For instance, the cells which form the vasculature of the glomerulus, a network of tiny blood vessels in the nephron (the functional unit of the kidney), are specialized for filtration. They contain numerous fenestrations, or pores, that allow certain components of the blood such as water, glucose, and nitrogenous waste to pass into the Bowman's capsule, the first step in urine formation. + +In addition, kidney blood vessel cells also play a vital role in maintaining hemostasis, or stable blood flow. Through the release of vasoactive substances, these cells can regulate the dilation or constriction of blood vessels, thereby controlling blood pressure and flow to the nephrons. On the other hand, the abnormal functioning of these cells can potentially lead to renal disorders such as kidney disease or hypertension. " DOI:10.1016/j.semcdb.2018.06.001|DOI:10.1146/annurev-physiol-052521-121841|DOI:10.1038/s41581-021-00411-9|DOI:10.1152/ajpregu.90960.2008 +592 CL:1000891 CL_1000891 "Kidney arterial blood vessel cells, also known as renal endothelial cells, form an integral part of the blood vessels that deliver blood to the kidneys. These cells have a unique and vital role in maintaining the structural integrity of the arterial walls, ensuring seamless and efficient transportation of blood to the nephrons. This vascular network is crucial to the functionality of the kidneys, which filter out waste products, control electrolyte balance, and regulate blood pressure. + +One of the primary functions of kidney arterial blood vessel cells is the regulation of blood flow within the kidney. They do this by releasing various vasodilators and vasoconstrictors that control the diameter of the blood vessels, thus influencing the rate and volume of blood reaching the renal tissue. Additionally, they possess a semi-permeable membrane that allows the selective transfer of solutes and fluids between the blood and surrounding tissues, which aids in maintaining homeostasis and body fluid balance. + +Furthermore, kidney arterial blood vessel cells play a fundamental role in the body's immune response. They interact with different components of the immune system, such as white blood cells, and respond to inflammation by promoting leukocyte adhesion and migration. Therefore, these cells not only supply nutrients and oxygen to the renal tissues but also have essential immunoregulatory functions." DOI:10.1038/s41581-021-00411-9|DOI:10.1053/j.mpaic.2006.04.002|DOI:10.1038/s41577-022-00694-4 +593 CL:1001225 CL_1001225 "Kidney collecting duct cells form an integral part of the urinary system and are primarily responsible for the final modifications to urine produced in the kidneys. These cells are located in the final channels of the nephrons, the microscopic structures in the kidney that are responsible for urine formation. The collecting duct system includes the cortical, outer medullary and inner medullary collecting ducts, which converge to pass urine through the renal papillae and into the minor calyces. + +The primary function of kidney collecting duct cells involves managing fluid and electrolyte balance and ensuring that homeostasis is achieved in the body. This is done through the selective reabsorption and secretion of different solutes like sodium and potassium, hydrogen ions, bicarbonate, and water. This is controlled by a range of hormones, including Antidiuretic Hormone (ADH), Aldosterone, and Parathyroid hormone (PTH). The reabsorption and secretion of these electrolytes play a vital role in maintaining the body's acid-base balance and blood pressure. + +Collecting duct cells can be further divided into principal cells and intercalated cells, each with their functional roles. Principal cells are chiefly responsible for the reabsorption of water and sodium and the secretion of potassium in response to ADH and aldosterone, where the water channels, Aquaporin-2, play a critical role. Intercalated cells serve to secrete and reabsorb hydrogen and bicarbonate ions to help maintain the body's pH balance. Dysfunctionality of these cells can lead to implications like renal tubular acidosis and disturbances in urine concentration, highlighting their importance in the urinary system." DOI:10.2215/CJN.08880914|DOI:10.2215/CJN.05760513|DOI:10.1073/pnas.1710964114|DOI:10.1016/j.krcp.2013.07.005 +594 CL:0000081 CL_0000081 "Blood cells, also known as hematologic cells, are integral to the body's survival within the circulatory system. Produced in the bone marrow and released into the bloodstream, these specialized cells contribute to maintaining overall equilibrium. The major types include red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes), each serving specific functions based on their structures. + +Erythrocytes, the most abundant, transport oxygen from the lungs to body tissues and carry carbon dioxide in the reverse direction. Their biconcave disc shape, rich in hemoglobin, enhances efficiency in oxygen and carbon dioxide transportation. Leukocytes, or white blood cells, defend the body against infections and foreign materials. Thrombocytes aid in blood clotting by forming a plug at damaged vessel sites, preventing bleeding and promoting healing. " https://www.ncbi.nlm.nih.gov/books/NBK2263/|DOI:10.1097/MOH.0000000000000621|DOI:10.1073/pnas.1615452113 +595 CL:0000127 CL_0000127 "Astrocytes, also called astroglial cells or macroglia, are characterized by a star-shaped structure. Their name is derived from the Greek words ""astro-"" meaning star and ""-cyte"" meaning cell. They are a predominant type of glial cell in the central nervous system. + +However, there are many subtypes of astrocytes including Bergmann glial cells, as well as immature, mature, and retinal astrocytes. Retinal astrocytes have been recognized as a unique subset of glial cells, and they seem to exert significant influences on both retinal development and the pathological loss of retinal ganglion cells. + +In the central nervous system, these cells play a vital role in the brain by providing structural and metabolic support to neurons. Astrocytes help maintain essential ion and neurotransmitter concentrations that are crucial for neural transmission. They also uphold the blood-brain barrier, protecting against harmful substances and contribute significantly to the repair and scarring process after brain and spinal cord injuries. Astrocytes are also implicated in several neurodegenerative diseases. Anomalies in astrocyte function in the central nervous system have been associated with disorders such as Alzheimer's, Huntington's, and Alexander disease." https://www.ncbi.nlm.nih.gov/books/NBK545142/|DOI:10.1007/s00401-009-0619-8|DOI:10.3389/fphar.2019.01114 +596 CL:0000149 CL_0000149 "Visual pigment cells, also known as photoreceptor cells or photoreceptors, are specialized neuronal cells located in the retina of the eye. There are two main types of visual pigment cells: rod cells, more sensitive to light, enabling vision in low light conditions (scotopic vision), and cone cells, responsible for color vision under normal light conditions (photopic vision). + +The specific structure of visual pigment cells underlies their function. Featuring an outer segment with stacks of membranous disks containing photopigment molecules, these cells undergo phototransduction when exposed to light. In this process, photons striking the molecules trigger a series of biochemical reactions, altering the cell's electrical charge. This process, known as phototransduction, alters the electrical charge inside the cell. The phototransduction cascade in rods is biochemically well-understood, with the activation of the photopigment rhodopsin triggering a change in membrane potential. The phototransduction process in cones is similar, but with different specific photopigments. + +To maintain light-sensing capability, visual pigment cells continuously renew their supply of photopigments. The renewal process occurs chronologically, with the oldest disks near the outer edge absorbing light first, while the youngest disks are closer to the cell body. This unique renewal mechanism ensures the continuous and efficient operation of visual pigment cells, enabling organisms to perceive visual cues from their environment. Thus, the intricate interplay between the structure and function of visual pigment cells is vital in the biology of vision." https://www.sciencedirect.com/topics/nursing-and-health-professions/visual-pigment|DOI:10.1242/jcs.175687|DOI:10.1016/j.bbabio.2013.08.009|https://www.ncbi.nlm.nih.gov/books/NBK52768/|https://www.sciencedirect.com/topics/medicine-and-dentistry/retina-cone +597 CL:0000135 CL_0000135 "Fibrocytes, also known as connective tissue cells, are essential components of the body's connective tissues, contributing significantly to tissue and organ structural integrity. Derived from mesenchymal stem cells, these spindle-shaped cells exhibit a distinct elongated body with minimal cytoplasm. Predominantly non-motile, fibrocytes display varying characteristics based on their specific locations within the body. + +The primary role of fibrocytes is the production and secretion of extracellular matrix (ECM) components, including collagens, elastin, proteoglycans, and fibronectin. These ECM components form a structural framework, or stroma, within organs and tissues, supporting the functionality of cells and blood vessels. The synthesis of collagen and fibrillar proteins by fibrocytes significantly influences wound healing, scar formation, and the development of fibrotic tissues. + +In pathological conditions like chronic inflammation, fibrocytes may undergo transformation into myofibroblasts, characterized by heightened contractile abilities. This transformation is implicated in the progression of fibrotic diseases marked by excessive ECM deposition. Additionally, fibrocytes contribute to immune responses by presenting antigens to T cells, aiding the body's defense against pathogens. The maintenance of tissue homeostasis by fibrocytes is crucial, and disturbances in this balance can lead to various connective tissue disorders." DOI:10.3389/fphar.2014.00123|DOI:10.1038/s41467-022-30633-9|DOI:10.3389/fimmu.2021.784401|DOI:10.1089/wound.2014.0561|DOI:10.1038/nm.2807 +598 CL:0000157 CL_0000157 "Surfactant-secreting cells, also known as Type II alveolar cells or pneumocytes, are specialized lung cells located within alveolar walls. While they represent 60% of the alveolar cell population, they only occupy 5–10% of the alveolar surface area. + +These cuboidal-shaped cells contain numerous lamellar bodies in their cytoplasm, serving as storage organelles for surfactant. The surfactant is a complex mixture of lipids and proteins, with phosphatidylcholine as the main lipid and SP-A, SP-B, SP-C, and SP-D as principal proteins. SP-B and SP-C play vital roles in reducing surface tension, while SP-A and SP-D contribute to innate immunity. + +Their primary function is to produce and release pulmonary surfactant, a crucial compound that reduces lung surface tension. This prevents alveolar collapse during exhalation and promotes efficient gas exchange during inhalation. Beyond surfactant production, these cells play a role in alveolar repair and regeneration. They can divide and differentiate into Type I alveolar cells, responding especially to lung injuries. Additionally, they regulate alveolar fluid balance by reabsorbing sodium and water, maintaining the thin liquid layer crucial for efficient gas exchange. " DOI:10.1513/AnnalsATS.201411-507FR|https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/type-ii-pneumocyte|DOI:10.1016/S0171-2985(98)80027-2|DOI:10.1016/B978-1-4557-3383-5.00008-7|DOI:10.3390/cells11132095 +599 CL:0000151 CL_0000151 "Secretory cells are found throughout the body, including epithelial and glandular tissues, and play a significant role in maintaining the body's homeostasis. They produce and secrete various substances, including hormones, enzymes, mucus, and sweat. Examples include stomach secretory cells producing gastric acid for digestion, pancreas cells generating insulin to regulate blood sugar levels, goblet cells in respiratory and intestinal tracts secreting lubricating mucus, and adrenal medulla chromaffin cells releasing adrenaline during stress. + +The process of secretion is intricately regulated and is typically initiated in response to specific signals. Upon receiving these signals, secretory cells generate the required substances and package them into vesicles—enclosed sac-like structures. These vesicles then move towards the cell membrane, merge with it, and release their contents through exocytosis. This synchronized production and secretion allow secretory cells to promptly respond to changes in the organism's internal and external environment, contributing to rapid adaptation. + +" https://www.ncbi.nlm.nih.gov/books/NBK535425/|DOI:10.1021/acsomega.3c06058|DOI:10.1111/imr.12182|DOI:10.1002/cphy.c190003 +600 CL:0000138 CL_0000138 "Chondrocytes are specialized cells derived from the mesenchyme. They are the only cells found in healthy cartilage, and their primary function is the synthesis and maintenance of the extracellular matrix of cartilaginous tissues. They synthesize various molecules essential for biomechanical function, including collagen types II, IX, and XI, link proteins, and proteoglycans like aggrecan and decorin. Beyond structural integrity, chondrocytes also contribute significantly to the homeostasis of articular cartilage in joints. + +The chondrocyte lifecycle involves proliferation, maturation, and hypertrophy, catering to growing, mature, and aging cartilage. Despite their typically low metabolic activity, conditions like osteoarthritis and rheumatoid arthritis can induce chondrocyte proliferation, leading to increased matrix production and the development of musculoskeletal issues. The unique extracellular matrix, rich in aggrecan, provides compression resistance, crucial for cartilage function in the musculoskeletal system." DOI:10.3390/jdb3040177|DOI:10.1177/19417381093504|DOI:10.1186/ar396|DOI:10.1002/art.34453 +601 CL:0000163 CL_0000163 "Endocrine cells are fundamental to the body's endocrine system, a complex network responsible for producing and releasing hormones directly into the circulatory system. These hormones act as chemical messengers, governing crucial bodily functions such as metabolism, growth, development, sexual function, and mood. They are located in the pancreas, thyroid, pituitary gland, and adrenal glands. + +In the pancreas, endocrine cells form clusters called the islets of Langerhans, housing alpha cells (producing glucagon), beta cells (producing insulin), and delta cells (producing somatostatin). Meanwhile, the thyroid gland's endocrine cells generate thyroid hormones (T4 and T3) crucial for energy regulation and metabolism. The pituitary gland's endocrine cells produce hormones like growth hormone (GH), prolactin (PRL), oxytocin, and vasopressin, regulating growth, lactation, and water balance. Conversely, endocrine cells in the adrenal glands secrete cortisol and adrenaline, influencing the body's stress response, blood pressure, and carbohydrate metabolism. + +The body's feedback mechanisms typically regulate endocrine cell activities, ensuring hormonal balance and organismal homeostasis. Disruptions in their normal functioning can lead to disorders such as diabetes, hyperthyroidism, and Addison's disease, underscoring the critical role of endocrine cells in maintaining bodily functions." https://www.ncbi.nlm.nih.gov/books/NBK279139/|https://www.ncbi.nlm.nih.gov/books/NBK459261/|https://www.ncbi.nlm.nih.gov/books/NBK537260/ +602 CL:0000183 CL_0000183 "Contractile cells play a key role in various physiological processes, primarily driven by their ability to change shape or contract in response to stimuli. This broad functionality spans from the muscle contraction involved in body movement to the rhythmic pumping of blood by the heart. + +The main components of contractile cells are muscle cells, encompassing cardiac, skeletal, and smooth muscle cells. Cardiomyocytes, the cardiac muscle cells, dictate the heart's pulse and rhythm, ensuring blood circulation. Skeletal muscle cells, or myocytes, regulate voluntary movements like walking or lifting, while smooth muscle cells, found in organs and tissues such as the gastrointestinal tract and blood vessels, control involuntary processes like blood flow and digestion. + +In addition to the muscle-specific contractile cells, the class also comprises other cells that exhibit contractile properties. Some examples of this include the contractile fibroblasts found in connective tissues, which can modulate their shape in response to various physiological stimuli. Contractile cells are also crucial in cellular mechanisms such as cytokinesis, where cells divide their cytoplasm during cell division. + + + + +" DOI:10.1016/B978-0-323-35775-3.00010-2|https://www.ncbi.nlm.nih.gov/books/NBK537139/|https://www.ncbi.nlm.nih.gov/books/NBK526125/|https://www.ncbi.nlm.nih.gov/books/NBK26831|DOI:10.3390/biom9050194 +603 CL:0000174 CL_0000174 "Steroid hormone-secreting cells are a specialized type of endocrine cell primarily responsible for the production and release of steroid hormones, complex molecules that play critical roles in a broad range of biological processes. These cells are typically found in the adrenal cortex, gonads (testes in males and ovaries in females), placenta, and some adipose tissues. The adrenal cortex, for instance, hosts cells that secrete cortisol, corticosterone, aldosterone, and adrenal androgens. The gonads produce sex hormones, such as estrogen, progesterone, and testosterone. + +Steroid hormone-secreting cells function through a remarkable biochemical machinery that involves the conversion of cholesterol into diverse steroid hormones. Steroidogenesis, the process of steroid hormone production, requires a series of enzyme-catalyzed reactions that modify the cholesterol molecule's structure. The produced hormones can diffuse across the cell membrane and travel through the bloodstream owing to their lipophilic nature, which allows them to easily penetrate target cells and regulate gene expression. + +The collective output of steroid hormone-secreting cells is pivotal for the orderly functioning of the human body. Steroid hormones act as key modulators of immune response, stress, cardiovascular activity, reproductive function, metabolism, and electrolyte balance, amongst other processes. Furthermore, aberrant functionality or dysregulation of steroid hormone-secreting cells can lead to several pathological conditions, including endocrine disorders, cardiovascular diseases, and cancers." DOI:10.1016/j.cll.2004.01.004|DOI:10.1038/s41435-021-00139-3|DOI:10.1210/edrv.32.4.zef579|DOI:10.1007/978-1-59259-829-8_4 +604 CL:0000010 CL_0000010 "A cultured cell refers to a cell that has been isolated from a living organism and put into an in vitro artificial environment conducive to its growth and proliferation. This environment typically consists of a flask or dish containing a nutrient solution or substrate known as a culture medium. The culture medium provides all the essential compounds needed for the cell's growth, including sugar for energy, amino acids for protein synthesis, salts to maintain chemical balances, and vitamins for various biological functions. + +Cultured cells include primary cultured cells and cell line cells. Primary cultured cells are derived directly from an organismal source, such as tissue taken from biopsies or surgeries. Cell lines are populations of immortalized cells that continue to survive and proliferate in culture. Primary cell cultures are often considered the best cellular models for replicating the functions of cells in vivo, while cell lines are useful tools as they are easier to maintain and are often derived from cancer cells, thus functioning as tools to research various cancers. + +In general, the aim of culturing cells is to encourage them to behave as they would in their natural environment, providing scientists with a miniature model version of the tissues or organ from which the cells came. They permit detailed study of the cell structure and the different cell processes that happen in the organism. By using cultured cells, scientists are able to conduct experiments that would be unethical or impractical on a living organism. Furthermore, cells in culture conditions are also employed in genetic engineering, vaccine production, and testing drug response. Consequently, the term ""cultured cell"" applies to a wide range of cells, all of which can be grown outside the body, retaining a number of their original properties and functions." DOI:10.1016/B978-0-12-803077-6.00009-6|DOI:10.3389/fcell.2021.711381|DOI:10.4161/spmg.19885|DOI:10.3390/cancers11081098 +605 CL:0000039 CL_0000039 "Germ line cells are a specific type of cell that are foundational in the reproduction of multicellular organisms. They are the cells responsible for passing on genetic information from one generation to the next. In humans and other mammals, germ line cells, through meiosis and fertilization, lead to the formation of germ cells: oocytes in females and spermatozoa in males. Germ line cells also include female and male germ line stem cells, which are the precursors for the oocytes and spermatozoa, respectively. + +In the early stages of embryonic development, germ line cells are separated from somatic cells, which are cells that will form body tissues and organs. Germ line stems cells undergo a specialized form of cell division called meiosis, which results in germ cells that have half the number of chromosomes of the parent cell. This reduction in genetic material is necessary to ensure that when the egg and sperm combine, the resulting offspring will have the correct number of chromosomes. + +Functionally, germ line cells serve a critical role in reproduction and the continuation of species. They not only carry the genetic information from parents to offspring, but also ensure the genetic diversity which is crucial for the evolution and survival of a species. Any alterations or mutations in these germ cells can directly pass onto the offspring, resulting in either a beneficial adaptation or a detriment. Thus, the meticulous regulation and proper functioning of germ line cells are crucial for reproduction and species propagation." DOI:10.1016/j.stem.2012.05.016|DOI:10.1016/j.gde.2014.09.011|DOI:10.1038/s41392-022-01197-3|DOI:10.3389/fcell.2020.00650 +606 CL:0000048 CL_0000048 "Multi fate stem cells, also known as multipotent stem cells, are a subclass of stem cell that possesses the ability to differentiate into multiple, but not all, cell types within the body. They are more specialized than pluripotent stem cells, which can transform into any cell type, but offer broader potential than oligopotent stem cells, which can differentiate into a smaller number of different cell types, or unipotent cells, which can only differentiate into a single type of cell. These properties make multi fate stem cells highly valuable tools in both the study of biological processes and in the potential treatment of a variety of diseases and conditions. + +Functionally, multi fate stem cells play a fundamental role in the ongoing maintenance and repair of specific tissues where they reside. This is due to their ability to generate a range of diverse cells specific to that tissue. As an example, a type of multipotent stem cell in the bone marrow known as a hematopoietic stem cell can differentiate into all types of cells that compose our blood and immune system. In a similar fashion, mesenchymal stem cells, another kind of multipotent stem cell found in bone marrow, can develop into a range of cell types including bone cells (osteocytes), muscle cells (myocytes), and fat cells (adipocytes). + +The most common type of stem cell therapy is multipotent hematopoietic stem cell transplantation, which can be used to replace a patient’s hematopoietic cells to address diseases that affect the hematopoietic system, such as leukemia or anemia. Aditional research is ongoing to determine the safety and effectiveness of multipotent stem cell therapies in other disease states." DOI:10.1186/s13287-019-1165-5|DOI:10.1002/jcp.25990 +607 CL:0000055 CL_0000055 "A non-terminally differentiated cell refers to a cell that has developed partway from a pluripotent stem cell, which is capable of differentiating into many different cell types, to a terminally differentiated cell type which typically does not differentiate any further. These cells play an essential role in the processes of growth, replenishment, and repair. They are in a transient state, having matured past the highly unspecified and pluripotent status of stem cells, but not yet completely specialized to perform the functions of any specific cell type. Their state is intermediate, making them malleable and versatile, capable of differentiating into several types of cells as needed. + +In terms of function, non-terminally differentiated cells have several roles. One of their general functions is to act as a reservoir of quickly-regenerating cells that can swiftly respond to the body's fluctuating needs. Conditions such as injury, illness, or routine cellular turnover can activate these cells. Once activated, these cells go through a series of finite maturation steps to differentiate into the specific cell type that the body currently requires, whether that be skin cells for wound healing or blood cells to combat infection. Other functions are specific to the type of non-terminally differentiated cell in question. +" DOI:10.1016/j.stem.2019.07.002 +608 CL:0000069 CL_0000069 "Branched duct epithelial cells are a specialized form of epithelial cells distinctively known for their branched structures and their location, found embedded within the epithelial linings of various ductal systems throughout the body. These cells normally line the ducts (tubular structures) of various organs, including but not limited to, the pancreas, salivary glands, and mammary glands. Their physical configuration, together with their position, allows them to function optimally in their respective physiological roles related to secretion and absorption. + +The primary function of branched duct epithelial cells is to produce and secrete certain substances required for the functioning of the body. For example, in the pancreas, they are involved in the production and secretion of digestive enzymes, while in the salivary and mammary glands, they are essential for the formation and transportation of saliva and milk respectively. The branched configuration of these cells significantly increases the surface area for the secretion of these substances, thereby supporting a higher production level.In addition, branched duct epithelial cells also play a vital role in protective mechanisms, acting as a barrier to prevent the entry of foreign substances into the ductal system. Their tightly packed arrangement ensures the regulation of the selective passage of materials in and out of the ducts. + +In short, branched duct epithelial cells are not only crucial for supporting the physiological processes tied to various organ systems, but they also sustain the fidelity of these systems through their protective roles, demonstrating their broad spectrum of functionality in human health." DOI:10.1111/odi.12201|DOI:10.1242/dev.104794|DOI:10.1016/bs.ctdb.2020.10.006|DOI:10.1186/bcr1368|DOI:10.4161/tisb.25933 +609 CL:0000072 CL_0000072 "Non-branched duct epithelial cells (NBDECs) are a unique type of cell that primarily form the structure of the duct system within various glands and organs in the body, such as the kidney collecting ducts and nasolacrimal drainage system. These cells are categorized by their lack of branching morphology, unlike other ductal epithelial cells. They are fundamental building blocks in the formation of unbranched tubular structures to facilitate the transfer of liquids from one part of an organ or gland to another. + +The main function of NBDECs is to line the ducts and provide a pathway for the transport of secretions. They play a crucial role in separating the lumen of the duct from the surrounding tissue, ensuring the safe passage of secreted materials. Their shape and structure are specifically adapted to this task, exhibiting properties of firm adhesion and low permeability. Hence, non-branched duct epithelial cells contribute significantly to maintaining the integrity and function of ductal systems. + +Beyond these structural and physiological roles, non-branched duct epithelial cells are essential in cellular communication and signal transduction associated with the secretion process. They have receptors on their surfaces that respond to hormonal or neural signals, thereby controlling the release and transport of substances through the ducts. Thus, NBDECs not only form the physical ""highway"" for substance transport but also regulate traffic on this highway, adjusting the amount and timing of substance release according to the body’s needs. Misfunction or damage to these cells can result in a disruption of normal secretion process and may lead to pathologic conditions." DOI:10.1038/ki.1995.391|DOI:10.1007/s004290050160|DOI:10.1095/biolreprod34.5.961|DOI:10.1097/IOP.0000000000000962|DOI:10.3390/ijms18122539 +610 CL:0000080 CL_0000080 "Circulating cells are a group of various cell types that circulate within the bodily fluids, particularly within the bloodstream and lymphatic system. These cells are fundamental to the living organism's functioning, playing vital roles in areas such as immunity, oxygen transport, and coagulation. Being in a state of perpetual motion allows these cells to react quickly and specifically to any physiological changes that occur in the body. + +The most common types of circulating cells are red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes). The primary function of red blood cells is to carry oxygen from the lungs to all body tissues and return carbon dioxide for expulsion. White blood cells, on the other hand, form the crux of the body's immune system, defending against foreign invaders like bacteria, viruses, and toxic substances. They are also involved in allergy responses. Platelets play a key role in maintaining hemostasis and preventing excessive bleeding by facilitating clot formation at sites of blood vessel injury. + +Other circulating cells such as endothelial circulating cells play vital roles in angiogenesis and maintaining vessel integrity. In contrast, circulating tumor cells, though typically present in very low numbers, have significant potential value in cancer diagnostics and therapeutic monitoring. Their dynamic state presents both opportunities and challenges in direct sampling and monitoring and could represent a vast wealth of information about a person's health status." DOI:10.1155/2019/2650429|DOI:10.1159/000213252|DOI:10.1002/stem.745|DOI:10.1146/annurev-med-062310-094219|DOI:10.1038/onc.2015.192 +611 CL:0000098 CL_0000098 "Sensory epithelial cells are specialized types of epithelial cells found in many sensory organs such as the nose and ears. These cells are crucial elements in the body's sophisticated sensory system, having the unique function of converting environmental stimuli into signals that can be processed by our brain. The nature and function of sensory epithelial cells depend on their location and the specific sensory organ they are part of. + +For instance, sensory epithelial cells within the nose, known as olfactory epithelial cells, detect airborne chemicals and relay this information to the brain to provide a sense of smell. Similarly, in the cochlea of the ear, we find auditory epithelial cells, a type of sensory epithelial cell specialized in capturing sound vibrations and converting them into electrical signals that can be interpreted by the brain for hearing. + +These sensory epithelial cells do not work alone but are part of a larger interconnected sensory network within each organ. In every case, they work in tandem with a variety of other cells, such as supporting sustentacular cells, basal cells, and nerve cells, to transduce environmental stimuli into signals that our brain can interpret. Importantly, disorders or damage to these cells can lead to sensory impairment or loss, reflecting their pertinent role in our sensory perception and understanding of the environment." DOI:10.1038/nrn1987|DOI:10.1002/jemt.1070230105|DOI:10.1080/01926230600713475|DOI:10.1016/j.biocel.2006.03.012|DOI:10.1016/j.heares.2012.11.010 +612 CL:0000115 CL_0000115 "Endothelial cells are specialized types of cells found lining the inner walls of blood vessels, lymphatic vessels and the heart. As a critical part of the cardiovascular system, they form a barrier, also known as endothelium, that separates the fluid component of blood and the walls of vessels. The endothelium represents the interface between circulating blood or lymph in the lumen and the rest of the vessel wall. + +Endothelial cells play numerous critical roles in maintaining homeostatic functions of the body. They regulate blood clotting by producing anticoagulant factors to prevent blood from clotting as it flows through blood vessels. Endothelial cells also mediate inflammation. During injury or infection, these cells produce molecules that promote the adherence of immune cells. This action helps direct the immune response to the site of inflammation or infection. Moreover, these cells are responsible for maintaining blood-fluid homeostasis. Endothelial cells allow selective permeability of substances from blood plasma to surrounding tissues and vice versa. This process facilitates the exchange of gases, nutrients, and metabolic waste products. + +Endothelial cells are not a homogenous population of cells; rather, they show great heterogeneity in structure and function, depending on their specific location and the type of blood or lymphatic vessel they inhabit. For example, in capillaries, they are extremely thin which allows for rapid exchange of substances, while in larger vessels they are more robust and play a role in injury repair. Additionally, the endothelial cells within arteries, veins, and lymphatics each have unique characteristics that are essential for their specialised functions. Despite this variety, all endothelial cells share a commonality in being the guardians of vascular integrity. " DOI:10.1038/s41569-022-00770-1|DOI:10.3390/ijms20184411|DOI:10.1089/ars.2014.6158|DOI:10.3390/cells10102712|DOI:10.1016/j.ajpath.2020.10.001 +613 CL:0000107 CL_0000107 "An autonomic neuron is a type of neuron that operates within the autonomic nervous system (ANS), the division of the nervous system that controls involuntary physiological functions. It plays a key role in maintaining homeostasis within the body by regulating various activities such as heart rate, digestion, respiratory rate, pupillary response, and urination. Autonomic neurons are critical for an organism's survival as they enable quick and adaptive responses to changes in the environment or internal physiological state. They act as fundamental intermediates, decoding central nervous system signals into actions at the level of individual effector organs. Structurally, autonomic neurons are typically multipolar, meaning they have one axon and several dendrites. Autonomic neurons synapse with effector cells (such as those muscles and glands innervated by the ANS) at specialized junctions called varicosities or neuroeffector junctions. + +These neurons can be further classified into two primary groups, sympathetic and parasympathetic neurons, each having its distinct functions and effects on the body. Sympathetic neurons are usually involved in 'fight or flight' responses, triggering reactions such as an increased heart rate, dilation of air passages allowing greater oxygen flow to the muscles, and slowing of digestion. On the other hand, parasympathetic neurons contribute to 'rest and digest' or 'feed and breed' activities that occur when the body is at rest, specifically stimulating digestion, activating metabolism, and helping the body to relax. Both sympathetic and parasympathetic neurons work together to ensure a balanced response to various stimuli, maintaining the equilibrium in the body." DOI:10.1016/B978-0-444-64032-1.00027-8|DOI:10.1016/S0301-0082(96)00039-1|DOI:10.1186/s13064-018-0117-6|DOI:10.1038/s41583-021-00523-y|DOI:10.1016/j.autneu.2010.03.002 +614 CL:0000128 CL_0000128 "Oligodendrocytes, also recognized as oligodendroglia, are a type of glial cell whose main functions are to provide support and insulation to axons in the central nervous system of some vertebrates, equivalent to the function performed by Schwann cells in the peripheral nervous system. Single oligodendrocytes can extend their processes to 50 axons, wrapping approximately 1 μm of myelin sheath around each axon. In contrast, Schwann cells can wrap around only one axon. Oligodendrocytes are the third most common type of cell in the central nervous system. + +One of the key functions of oligodendrocytes is the production of the myelin sheath, a fatty, protective covering that accelerates the propagation of nerve impulses through neurons, thus improving nerve signal transmission. Oligodendrocytes do this by wrapping the myelin around the axons of neurons in a process called myelination. This insulation also helps prevent electrical signals from dispersing out from the axon, maintaining the quality and speed of the electrical signals along the nerve cells. Therefore, oligodendrocytes play an indispensable role in maintaining and regulating the efficiency of the electrical communication system in the central nervous system. + +Oligodendrocytes carry out other functions that are critical for the sustenance and preservation of the overall health of neurons. For instance, they play a role in supplying neurons with critical nutrients. Additionally, they regulate the concentration of ions in the extracellular environment of neurons and adjust the electrical activities of neurons. Dysfunction or loss of oligodendrocytes can lead to widespread neurological disorders such as multiple sclerosis where the immune system mistakenly attacks the myelin sheath, leading to poor transmission of electrical signals along the neurons. +" DOI:10.1101/cshperspect.a020479|DOI:10.1016/j.neuroscience.2013.11.029|DOI:10.1016/j.neuroscience.2013.06.047|DOI:10.1172/JCI90610|DOI:10.1007/978-3-319-47861-6_7 +615 CL:0000152 CL_0000152 "Exocrine cells are specialized cells that produce and secrete substances into ducts, which then transport these substances onto body surfaces or into body cavities. They form an integral part of the exocrine glands, which are one of the two main types of glands in the human body, the other being endocrine glands. Exocrine cells release the substances they produce through a mechanism known as exocytosis. These substances produced by exocrine cells are extremely varied and include sweat, saliva, mucus, digestive enzymes, and milk. + +Exocrine cells are highly diverse and are found throughout the body, differentiated according to the specific substances they secrete. For instance, in the sebaceous gland, exocrine cells known as sebum secreting cells secrete sebum, which helps keep the skin moisturized. In the pancreas, pancreatic acinar cells are exocrine cells that are grouped together in clusters known as acini, secreting digestive enzymes into the small intestine. + +The function of exocrine cells, therefore, is largely dependent on the secretion they produce and where in the body they are located. They help maintain homeostasis in the body, supporting processes such as digestion, maintaining skin health, and assisting in body temperature regulation. Dysfunction or disease of these cells can lead to various disorders, such as cystic fibrosis, where mucus-secreting exocrine cells produce abnormally thick and sticky mucus. Thus, the role of exocrine cells is critical in the normal operation of multiple bodily functions." DOI:10.1007/s10911-006-9031-3|DOI:10.1242/dev.197657|DOI:10.1152/physrev.00031.2002|DOI:10.1136/gut.2005.065946|DOI:10.1016/j.prrv.2007.02.004 +616 CL:0000154 CL_0000154 "Protein secreting cells, often referred to as secretory cells, are diversified cells specialized in synthesizing and releasing specific proteins into the bloodstream or extracellular environment. They play a pivotal role in various physiological processes across different organ systems. The structure of these cells is uniquely designed to facilitate their high protein production rate, often characterized by an expanded endoplasmic reticulum and abundant Golgi apparatuses, structures instrumental in protein synthesis and transportation. + +Given that various proteins serve multiple functions in the human body, each protein-secreting cell is generally adapted to a certain type of protein production that aligns with their location and role. For example, pancreatic acinar cells secrete digestive enzymes into the digestive tract to facilitate nutrient breakdown and absorption. Similarly, insulin secreting cells produce and secrete the peptide hormone insulin into the bloodstream, allowing regulation of blood sugar levels. Importantly, the regulation of protein secretion from these cells is tightly controlled through intracellular signaling pathways. Any disruption or dysfunction in these pathways can lead to various pathological conditions. For example, a dysfunction in insulin secreting cells can result in diabetes. +" DOI:10.1101/cshperspect.a012872|DOI:10.1146/annurev.cellbio.16.1.557|DOI:10.1038/nature04377|DOI:10.1038/s41580-020-00317-7 +617 CL:0000159 CL_0000159 "Seromucous secreting cells are a specialized cell type prominently found lining the mucosal surface of various body parts, including the nasal passages, lungs, stomach, intestines, and the respiratory tract. These cells play a crucial role in manufacturing and secreting key proteins and mucus necessary for the body to function optimally. + +Functionally, seromucous secreting cells are critical players in barrier maintenance and immune defense mechanisms of the body. Their primary role is to produce and secrete mucins, the primary component of mucus. Mucin is a glycoprotein, which forms mucus when combined with water and other components. The role of mucus within the body is multi-faceted, serving to lubricate internal surfaces, protect surfaces from particle adherence, and present a barrier to potential pathogens. The dual nature of these cells means they also secrete serous fluid, composed largely of water and enzymes. This fluid aids in lubrication, augmenting the function of the sticky mucus by helping moisten and support the body's epithelial surfaces. + +While seromucous secreting cells function uniformly, their distribution varies depending upon the specific organ system. For example, in the respiratory tract, they are responsible for the ""mucociliary escalator"" mechanism that enables foreign particles and microorganisms trapped in mucus to be continually swept away from the lungs towards the pharynx. In the digestive system, these cells contribute to the formation of the protective mucus layer that coats the stomach lining, shielding it from the acidic gastric juices. The vital role of seromucous secreting cells in maintaining overall cellular homeostasis makes them a prime contributor to the body's health and wellbeing." DOI:10.1007/s004180050306|DOI:10.1097/MLG.0b013e3180383651|DOI:10.1183/09031936.97.10071655|DOI:10.1152/ajplung.1994.267.2.L206|DOI:10.1038/nrgastro.2013.35 +618 CL:0000147 CL_0000147 "Pigment cells, which includes melanocytes, are specialized types of cells predominantly known for their role in the production and distribution of pigment, or color, in numerous organisms. The type and concentration of pigments produced by these cells in different parts of an organism’s body significantly contribute to its outward characteristics such as skin, hair, and eye color in humans. These cells reside in the basal layer of the skin epidermis, hair follicles, inner ear, uveal tract of the eye, and certain parts of the brain and heart. + +The primary function of pigment cells is synthesizing and storing a pigment known as melanin through a process called melanogenesis. The produced pigment is packaged into small vesicles called melanosomes, which are then transported along the cellular projections to keratinocytes, which are skin cells that make up about 90% of the outermost layer of human skin. The asymmetrically distributed melanosomes absorb and/or scatter the ultraviolet radiation in sunlight, thereby providing a protective shield against potential DNA damage, apoptosis, and skin cancer. Also, genetic differences in melanin production and transport is a mechanism that contributes to the variation in skin color between populations with different sunlight environments. + +Pigment cells are also implicated in a host of biological roles beyond pigmentation. They play a role in the immune system and inflammatory responses, can influence visual and hearing functions, and their ion-transport capabilities contribute to inner ear fluid homeostasis. Alterations in pigment cells can lead to several diseases such as albinism, vitiligo, and melanoma. Therefore, pigment cells are important for their protective role in skin and other organs, while their impairment can have serious health impacts." DOI:10.1146/annurev.cellbio.19.111401.092937|DOI:10.1111/pcmr.12121|DOI:10.1111/j.1751-1097.2007.00226.x|DOI:10.1146/annurev.genet.37.110801.143233|DOI:10.1080/21695717.2018.1461488 +619 CL:0000153 CL_0000153 "A glycosaminoglycan secreting cell is a specialized cell type that produces and secretes glycosaminoglycans, which are large linear polysaccharides made up of a varying sequence of two alternating sugars. Their primary function lies in maintaining and supporting the collagen and elastin present in the extracellular matrix, which provides structure and support to cells. In addition, these cells maintain our body's level of hydration and help in wound healing, development and cell-to-cell communication processes. + +Glycosaminoglycan synthesis is a diverse process that depends on the specific type or class glycosaminoglycan. Their synthesis can occur in the cytoplasm and may involve the endoplasmic reticulum and Golgi apparatus. Glycosaminoglycans are assembled through polymerization, and eventually make their way to the cell membrane, where they are secreted into the extracellular environment. + +Glycosaminoglycan secreting cells also provide a source of glycosaminoglycans for proteoglycan synthesis, which are a critical component of the extracellular matrix. The proteoglycans, formed by the combination of proteins and glycosaminoglycans, interact with water to create a fluid-filled matrix that offers resistance to compressive forces, demonstrating its importance in regions like cartilage. Moreover, glycosaminoglycan secreting cells have been found to be more prevalent in the skin, blood vessels, and various tissues in the body, playing a crucial role in maintaining the structural integrity of these tissues. These cells are not only involved in the internal working of organs but also in the interaction mechanism between cells. " DOI:10.3390/biom5032003|DOI:10.1073/pnas.2116718119|DOI:10.1155/2015/834893|DOI:10.3390/ph11010027 +620 CL:0000167 CL_0000167 "Peptide hormone secreting cells are specialized cells that produce and release peptide hormones into the body. These cells exist in several organs, including but not limited to the thyroid gland, parathyroid gland, and adrenal gland, in the gastric lining of the stomach and intestine, and in the pancreatic islets in the pancreas. Peptide hormones are short chains of amino acids and are a class of hormones with important functions in the body. + +The function of peptide hormone secreting cells is to secrete peptide hormones that regulate various physiological activities. The type and function of the peptide hormone secreted depends on the specific specialization of these cells, which depends on their tissue context. Some types of peptide hormones are involved in controlling metabolism, regulating immune system activity, maintaining homeostasis, stimulating growth and development, and controlling reproductive processes. These cells react to specific signals and cues from the body and respond by releasing their hormones. The released hormones then travel via the bloodstream to their target cells where they bind to specific receptors, triggering a response. + +The synthesis and secretion of peptide hormones is a complex metabolic process. First, the peptide hormone secreting cells synthesize the hormone as a precursor, often larger than the active hormone itself, which ensures correct folding and processing. The precursor hormone is then sent to the Golgi apparatus for further processing, which often includes the cleavage of the precursor into the active form of the hormone, and then packaged into secretory vesicles. Upon receiving a signal, these cells release the hormone into the extracellular space in a process known as exocytosis, from where they enter the bloodstream to function. The specificity of peptide hormone action is due to the specific receptors on their target cells, ensuring that they elicit the desired response where it is necessary. Thus, peptide hormone secreting cells play a prominent role in maintaining the body’s physiological stability." DOI:10.1007/s001250051322|DOI:10.1016/j.tem.2006.10.011|DOI:10.1002/dvdy.21573|DOI:10.1210/me.2008-0209|DOI:10.1210/er.2005-0034 +621 CL:0000170 CL_0000170 "Glucagon secreting cells, also known as alpha cells, are a type of peptide hormone secreting cell that constitute approximately 20% of the cells in the islets of Langerhans in the pancreas. These cells are scattered throughout the islet but are often found towards the periphery. The primary role of these cells is the production and secretion of the peptide hormone glucagon—a critical component in the regulation of blood glucose levels. The hormone is named for its ability to induce glycogenolysis in the liver, which results in the breakdown of stored glycogen into glucose, thereby increasing blood glucose levels. + +The function of glucagon secreting cells is vital in maintaining energy homeostasis. When blood glucose levels drop—such as during times of fasting or between meals—glucagon secreting cells respond by releasing glucagon into the bloodstream. The hormone travels to the liver, binding to glucagon receptors on hepatocytes. This binding initiates signaling pathways that activate enzymes responsible for glycogenolysis and gluconeogenesis, the formation of glucose from noncarbohydrate sources. Thus, glucagon acts as a counter-regulatory hormone to insulin, which promotes glucose storage and lowers circulating glucose levels. + +Furthermore, glucagon secreting cells serve a significant role in pathological conditions like diabetes mellitus. In type 1 diabetes, where there is a relative or absolute lack of insulin, excessive glucagon secretion can exacerbate hyperglycemia, or high blood sugar. Conversely, in type 2 diabetes, glucagon secretion may be inappropriately elevated or reduced, contributing to the dysregulation of glucose homeostasis.Glucagon secreting cells is therefore crucial in normal physiology, but also their dysregulation contributes to disease conditions." DOI:10.2337/db09-1177|DOI:10.1530/JOE-23-0081|DOI:10.1152/ajpendo.00492.2002|DOI:10.1530/JOE-22-0298|DOI:10.1038/s41574-018-0097-y +622 CL:0000172 CL_0000172 "Somatostatin secreting cells, also known as delta cells, D cells or type D enteroendocrine cells, are specialized endocrine cells primarily found within the pancreas and in the gastrointestinal (GI) tract. They are a component of the islets of Langerhans in the pancreas, residing alongside other endocrine cells such as alpha, beta, and epsilon cells. Outside of the pancreas, they also inhabit the antral region of the stomach and the duodenum, thus playing dual roles in both the digestive and endocrine systems. + +The primary function of these cells is the synthesis and release of somatostatin, a peptide hormone with inhibitory effects on the secretion of other hormones. In the pancreas, somatostatin secreting cells play a regulatory role by dampening the activity of both insulin and glucagon hormones. This happens by suppressing the secretion of insulin from beta cells and glucagon from alpha cells, therefore, maintaining glucose homeostasis. In the gastrointestinal system, they limit the secretion of gastrin, a hormone that stimulates the secretion of gastric acids to digest food and helps facilitate movement in the stomach and intestines. + +Furthermore, somatostatin secreted from these D cells also regulates the rate of cell proliferation and differentiation, and has been found to inhibit the release of growth hormone, thereby modulating the growth processes of the body. This regulatory role of being a ‘universal inhibitor’ confers on somatostatin secreting cells a significant function in not only maintaining glucose and acid balance but also in controlling cell growth and proliferation. Anomalies in the normal functioning of these cells, such as the development of tumours can occur and are known as somatostatinomas. The overproduction of somatostatin by these tumours could lead to diseases like diabetes, or digestive conditions like Zollinger-Ellison syndrome. Thus, these cells are invaluable to the homeostatic equilibrium of the body." DOI:10.1038/s41574-018-0020-6|DOI:10.1210/endo.141.1.7263|DOI:10.1159/000197691|DOI:10.1016/j.pharmthera.2004.02.002|DOI:10.1111/j.1440-1746.2007.05053.x +623 CL:0000168 CL_0000168 "Insulin secreting cells, also known as beta cells or type B pancreatic cells, are a specific type of cell found abundantly in the pancreas. They form part of the larger group of cells known as the islets of Langerhans, which are responsible for hormone production within the pancreas. Named after a German pathologist, the islets of Langerhans consist of different types of cells, each responsible for producing different hormones. Insulin secreting cells have been identified as elliptical or spherical in shape, and occupy about 65-80% of the total islet cells. They are distinguished by their cytoplasm filled with insulin-storing granules, and by their rich blood supply which is vital for insulin delivery to the body. + +Insulin secreting cells have the crucial function of secreting insulin, a critical hormone necessary for glucose regulation in the body. The process of insulin secretion is initiated when the blood glucose level increases, typically after meals. The glucose molecules are transported into the beta cells via glucose transporters. These glucose molecules are then metabolized, resulting in an increased energy concentration within the cells, in the form of the molecule ATP. The rise in ATP subsequently leads to the closing of ATP-sensitive potassium channels, causing the insulin secreting beta cell to depolarize and leading to the opening of the voltage-gated calcium channels. The influx of calcium ions into the cells triggers the fusion of insulin-containing vesicles with the plasma membrane, releasing insulin into the bloodstream. + +The secreted insulin has wide-ranging impacts on various tissues and organs. It primarily enables the body's cells to uptake glucose from the bloodstream and use it for energy metabolism. In addition, when there's excess glucose, insulin assists in storing it in the liver and releasing it when the body needs it. Insulin also inhibits the liver from producing glucose. Insulin also regulates lipid metabolism by facilitating the storage of lipids and by inhibiting lipolysis. Problems with insulin secretion, such as in type 1 diabetes where beta cells are destroyed, or in type 2 diabetes where the body's cells become resistant to insulin, can have serious implications on sugar regulation in the body, and ultimately lead to significant health complications." DOI:10.1038/s41574-021-00568-0|DOI:10.1038/s41580-020-00317-7|DOI:10.1016/j.cmet.2022.06.003|DOI:10.1016/j.biochi.2015.10.024|DOI:10.1007/s00125-005-0100-8 +624 CL:0000206 CL_0000206 "Chemoreceptor cells, also recognized as chemosensory cells, are highly specialized cells tasked with detecting chemical changes in their environment. These cells communicate between the outside world and an organism's internal system to allow the body to adapt to environmental changes. They form a fundamental part of various physiological systems and serve as the building blocks in the chemical sensory system, including taste, smell, and internal chemosensation mechanisms in the body. + +Functionally, chemoreceptor cells are perhaps best known for their role in the respiratory centers of the brain. In this context, they monitor the levels of carbon dioxide (CO2) and oxygen (O2) in the blood, as well as the pH level, triggering appropriate responses if these parameters move outside of a narrow, regulated range. Significant changes in these values may indicate issues such as ingestion of toxins or the onset of hypoxia, and the chemoreceptor cells ensure that rapid responses can be triggered to restore equilibrium, including alterations in breathing rate or renal function. + +Chemoreceptor cells also play crucial roles in other parts of the body. In the gustatory system, they work as primary sensory receptors for taste. Within the olfactory system, they detect odors, while in the carotid and aortic bodies, they respond to changes in blood chemistry. Inside the gastrointestinal tract, they sense changes in nutrient concentration and pH. Each chemoreceptor cell is tailored towards a specific chemosensation task, aiding in differentiating between various chemicals and triggering specific responses. This ability to sense a broad array of chemical changes is paramount to the body's capacity for homeostasis, survival, and interaction with the environment." DOI:10.1111/j.1748-1716.2011.02308.x|DOI:10.1152/physrev.00003.2019|DOI:10.1016/j.pneurobio.2005.03.001|DOI:10.1080/10409230701693359|DOI:10.1038/s41467-021-24444-7 +625 CL:0000213 CL_0000213 "Lining cells are a major type of cell that covers the exterior surface of the body and lines internal cavities and passageways for various organs. These cells serve as the first line of defense against physical and biological aggressors by providing a physical barrier that protects the underlying structures. + +These cells play a multifunctional role and depend on the specific regions they cover. In the digestive tract, they facilitate the absorption of nutrients and elimination of waste products. In the circulatory system, they line the interior surface of blood vessels. In the respiratory system, they remove harmful particles from the air we breathe. In addition, lining cells also play an indispensable role in fluid and electrolyte balance, immune response, and other physiological processes. + +One characteristic feature of lining cells is their capability of regeneration. A rapid turnover of these cells aids in the healing process, allowing the body to speedily recover from both internal and external injuries. Moreover, different types of lining cells can be recognised based on their unique shapes— squamous, cuboidal, and columnar, which correspond to their specific tasks and locations in the body. This diversity extends to their arrangements as well, which can be either single or stratified, directly correlating to the amount of protection required for that particular area of the body. Thus, lining cells' primary functions lie in protection, absorption, secretion, and transcellular transport." DOI:10.1016/S1357-2725(03)00242-5|DOI:10.1177/019262339602400114|DOI:10.1016/0049-0172(85)90007-1|DOI:10.1007/s00204-016-1794-8|DOI:10.1016/j.immuni.2015.07.007 +626 CL:0000215 CL_0000215 "Barrier cells, also known as barrier epithelial cells, constitute a unique cell type that primarily functions as a physical barrier to protect the organism from various external factors, such as pathogens, allergens, and toxins. This subset of cells mainly comprises the mesothelial cells of various organs inner lining of the gastrointestinal tract, and the epithelial layer of airways and blood vessels. + +In addition to their protective barrier function, barrier cells are often involved in selective transport of molecules, secretion of substances, and sensory reception. For instance, in the lining of the stomach and intestines, barrier cells secrete mucus which protects the cells from gastric acids and enzymes, while aiding digestion and nutrient absorption. In the airways, these cells have cilia which move mucus and trapped particles upward for expulsion. Similarly, barrier cells within the lining of blood vessels regulate the exchange of nutrients, metabolic products, and waste between blood and tissues. Hence, barrier cells play an essential role in various body systems, contributing to the overall health and wellbeing of an organism." DOI:10.1146/annurev.pathol.4.110807.092135|DOI:10.1016/S1357-2725(03)00242-5|DOI:10.1007/s00535-016-1207-z|DOI:10.1016/j.immuni.2015.07.007|DOI:10.4161/21688370.2014.978720 +627 CL:0000197 CL_0000197 "Sensory receptor cells are specialized types of cells that respond to specific types of stimuli such as light, sound, pressure, heat, or chemical changes. They act as transducers by converting external or internal environmental stimuli into electrochemical signals that the nervous system can process and interpret. These cells are situated throughout the body and form essential components of the sensory nervous system, facilitating the ability of an organism to interact with its environment. + +Sensory receptor cells have distinct structural variations depending on the type of stimulus they are meant to perceive. For example, photoreceptor cells in the eyes have a unique structure that can absorb and transduce light into electrical signals, enabling vision. Similarly, within the auditory system, ear hair cells in the cochlea translate the mechanical energy from sound waves into electrical signals that lead to the perception of sound. Other types of sensory receptor cells include thermoreceptor cells, which respond to changes in temperature, and pain receptor cells, which can detect potentially harmful stimuli that cause pain. + +The functions of sensory receptor cells are not just limited to simple signal conversion. They also exhibit adaptation, a mechanism by which they can adjust their sensitivity to a consistent stimulus. For example, the feeling of clothes on the skin is initially strong, but the sensory receptor cells quickly adapt, and the sensation becomes less noticeable. These cells also have a vital role in homeostasis, with certain specialized types of chemoreceptor cells functioning to monitor internal conditions such as pH, blood pressure, and levels of oxygen and carbon dioxide. Thus, sensory receptor cells form an essential link between the physical world and our perception of it, influencing a wide range of physiological processes." DOI:10.1523/JNEUROSCI.15-12-07757.1995|DOI:10.3389/fncel.2021.761416|DOI:10.1038/nrn1828|DOI:10.1002/neu.20079|DOI:10.1152/ajprenal.00252.2013 +628 CL:0000219 CL_0000219 "A motile cell is a unique type of cell that possesses the ability to move independently, often through the generation of contractile proteins within the cell structure. While many cells in multicellular organisms exhibit some degree of movement, motile cells distinguish themselves with a higher capacity for controlled, self-propelled motion. The source of this mobility is largely dependent on cellular structures such as flagella, cilia, or the ability to alter cell shape via pseudopodia. Their movements can be either random or directed towards specific signals, a process scientifically referred to as chemotaxis. + +Motile cells undertake a wide range of complex and crucial functions. For instance, cells of the immune system like neutrophils and macrophages exhibit motility, allowing them to seek out and destroy foreign pathogens in the body. Similarly, sperm cells, being highly active motile cells, depend on their flagella for movement towards the oocyte or egg to facilitate sexual reproduction. + +Mechanistic understanding of the dynamics of motile cells is pivotal in several biomedical applications. For instance, cancer cells acquire abnormal phenotypes from motile cells that aids in invasive growth and metastasis, leading to the spread of the disease. In contrast, impaired cell motility can lead to health issues as in Primary Ciliary Dyskinesia, a disorder characterized by defects in the action of cilia lining the respiratory tract and elsewhere, leading to recurrent infections. " DOI:10.1146/annurev.bioeng.7.060804.100340|DOI:10.1126/science.1221063|DOI:10.1189/jlb.68.5.593|DOI:10.1038/nrc.2018.15|DOI:10.3233/TRD-190036 +629 CL:0000212 CL_0000212 "Absorptive cells, also known as enterocytes, are specialized eukaryotic cells forming the majority of the epithelial lining in the small and large intestines of the gastrointestinal tract. These distinct cells are notable for their significant role in the absorption of nutrients from the food we consume. Specifically, these cells are responsible for the crucial function of absorbing water, electrolytes, and nutrients, such as carbohydrates, proteins, and lipids, broken down from the digestive process. + +The surface of each absorptive cell is covered with microvilli, small, finger-like projections that increase the cell's surface area to optimize its absorption capacity. The larger surface area provided by the microvilli maximizes the exposure of the cell's membrane to the content of the intestinal lumen, facilitating the efficient uptake of digested nutrients. Nutrients pass through these cells and then enter the bloodstream or the lymphatic system, contributing to the body's nourishment, energy supply, and overall metabolic functions. + +Absorptive cells have additional functions as complex actors in body homeostasis by playing an integral role in immune responses and intercellular communication. These cells can recognize pathogenic organisms and secretory antibodies to counteract their harmful effects. Absorptive cells also influence the intestinal microenvironment by sending signals and interacting with neighboring cells - a critical part in maintaining the health and functions of the body's digestive system. Their role extends beyond simple nutrient absorption, emphasizing their importance in overall body health. +" DOI:10.1038/nrg1840|DOI:10.1016/j.bpg.2016.02.007|DOI:10.1242/dev.135400|DOI:10.1016/j.chom.2016.03.003|DOI:10.1038/s41575-021-00423-7 +630 CL:0000211 CL_0000211 "Electrically active cells comprise a major and specialized cell type known for their unique ability to generate and propagate electrical signals. These cells are mainly found within the nervous system, cardiac muscle, and skeletal muscle tissues, playing significant roles in transmitting information, muscle contraction, and maintenance of the body's homeostasis. + +Electrically active cells function through an intricate process involving a sudden alteration in the cells' electrical potential. This is facilitated by the selective movement of ions across the cell's membrane, disrupting the electrochemical equilibrium. This process, also known as an action potential, is what allows these cells to transmit signals rapidly over long distances. In the nervous system, neurons transduce sensory stimuli into electrical potentials. This mechanism enables signal transmission from different body parts to the brain, facilitating complex functions such as thought, memory, and movement. In the cardiac and skeletal muscle tissues, electrically active cells propagate electrical signals that lead to a synchronized muscle contraction, enabling heartbeat and movement, respectively. + +The activity of these cells is regulated through various ion channels, synaptic activity, and specific neurotransmitters. Disruption in the normal activity of these regulators can lead to severe neurological and muscular diseases, such as myasthenia gravis, epilepsy, and cardiomyopathy. Thus, electrical signals and their proper transmission in electrically active cells is integral for maintaining normal homeostasis. " DOI:10.1038/nn753|DOI:10.1152/ajpheart.1983.244.1.H3|DOI:10.1007/s12551-013-0135-x|DOI:10.1016/j.expneurol.2015.01.007|DOI:10.15420/aer.2016.4.3 +631 CL:0000226 CL_0000226 "A single nucleate cell is a fundamental cell type found across a wide array of organisms, from simpler unicellular organisms to much more complex multicellular organisms including humans. Characterized by its possession of a single nucleus, which contains DNA, the genetic material of the cell which is crucial for the cell's overall function, survival, and the potential to replicate. + +Functionally, the single nucleate cell carries out a multitude of tasks essential to life, largely dependent on the specific type of cell and organism in which it is found. In multicellular organisms, the presence of a single nucleus helps in encoding all the necessary information for the growth, development, and function of the organism. This single nucleus serves as a command center, controlling the metabolic activities of the cell and thereby influencing the organism's organic traits. + +The DNA within the nucleus of the single nucleate cell is transcribed to RNA, which is further translated into proteins that perform diverse functions - enzymes catalyzing biochemical reactions, structural proteins giving cell its shape, transport proteins moving nutrients and wastes, to name a few. Beyond its crucial role in protein synthesis, the single nucleate cell's nucleus also plays a vital role during cell division, where the DNA is replicated and divided between two daughter cells. Hence, a single nucleate cell encapsulates the essentials of life - regulating biochemistry, carrying genetic inheritance, and providing for growth and reproduction. +" DOI:10.1016/j.ceb.2014.01.003|DOI:10.1038/nrm.2016.153|DOI:10.1242/jcs.037333 +632 CL:0000221 CL_0000221 "Ectodermal cells are key components of the ectoderm, one of the three primary germ layers formed during the early stages of embryonic development in multicellular organisms. These cells delineate into tissues and structures associated with the integumentary and nervous systems. The ectodermal layer, and thus ectodermal cells, are essential for the formation of the skin, hair, nails, lens of the eye, the epithelium of the mouth and nose, and the nervous system including the brain and spinal cord. + +The role of ectodermal cells largely depends on the specific organism, its developmental stage, and the location of these cells within the body. During the embryonic phase, ectodermal cells play a significant role in organogenesis. Organogenesis is the process through which the ectoderm, mesoderm, and endoderm develop into the internal organs of the organism. This process involves multiple signaling pathways, cellular migration, developmental molecules and differentiation. + +Some examples of the diversity of cell types and structures derived from ectodermal cells include the formation of the neural crest cells and neural tube, which give rise to multiple organ systems, including portions of the craniofacial skeleton, the peripheral nervous system, and the adrenal glands. Additionally, subsets of ectodermal cells are intrinsically linked in the formation of the lens and cornea of the eyes. Genetic mutations in the function of these cells during embryonic development can result in conditions such as ectodermal dysplasias, characterized by abnormal development of skin, hair, nails, teeth, or sweat glands. Thus, ectodermal cell functioning is critical in both the developmental phase and throughout life." DOI:10.1007/s00109-012-0908-x|DOI:10.1016/S0012-1606(03)00325-7|DOI:10.1371/journal.pbio.2004045|DOI:10.1016/j.ydbio.2012.01.006|DOI:10.1002/ajmg.a.61045 +633 CL:0000225 CL_0000225 "Anucleate cells are cells that lack a nucleus. This unique characteristic dramatically impacts their function and life cycle compared to single nucleate cells. These cells have a simplified cellular architecture and carry out very specific functions in the body. + +One of the most common types of anucleate cells in mammals are the mature red blood cells (RBCs), also known as enucleate erythrocytes. RBCs are initially produced in the bone marrow with a nucleus, but the cell expels its nucleus upon maturity. This process allows more space for hemoglobin, the oxygen-carrying protein. Functionally, erythrocytes are responsible for delivering oxygen from the lungs to the body's tissues and returning carbon dioxide back to the lungs. These disc-shaped cells are highly flexible, allowing them to maneuver through the tiniest blood vessels. + +Anucleate cells significantly contribute to the organism's function, however the absence of a nucleus imposes several limitations. These cells cannot divide and repair themselves, which results in a shortened lifespan. For example, human RBCs only live about 120 days. RBCs also lack mitochondria, which forces them to produce energy anaerobically, ensuring they do not consume the oxygen they transport. The absence of nucleus hampers protein synthesis, making these cells less adaptable to changes in their environment compared to nucleated cells. Other types of anucleate cells include platelets which play a critical role in the clotting process during injury. The absence of a nucleus in platelets prevents unnecessary clotting, as they cannot respond to external growth factors. Overall, anucleate cells represent a specialized adaptation to specific roles within the organism. Although they lack a nucleus, their unique structure and function within the body are essential for homeostasis." DOI:10.1016/j.tcb.2011.04.003|DOI:10.4061/2011/139851|DOI:10.1055/s-2007-969027|DOI:10.1055/s-2004-833484 +634 CL:0000237 CL_0000237 "Keratinizing barrier epithelial cells are one of the specialized cell types that make up the epithelium. Found predominantly in the epidermis, which is one of the layers of skin, these cells incorporate a unique structural protein known as keratin. Keratin promotes cell rigidity and fortification, allowing the skin and other epithelial surfaces to act as a barrier against environmental insults such as pathogens, chemicals, and physical trauma. Also, these cells help maintain body hygiene by trapping bacteria and preventing their penetration and systemic dissemination. + +The primary function of keratinizing barrier epithelial cells includes the formation of a stratified squamous epithelium, an essential facet of skin architecture. This structure comprises several layers of cells with different shapes and sizes, where cells in the topmost layer often contain high levels of keratin. During the process of keratinization, these cells undergo terminal differentiation, cease to divide, lose their nuclei and other organelles, and eventually form an outer layer of dead but mechanically potent cells, constituting the skin's uppermost ‘horny’ layer or stratum corneum. + +Aside from acting as the body's first line of defense, keratinizing barrier epithelial cells have a variety of other functions. They play a role in the regulation of body temperature and limit the loss of water, electrolytes, and other essential body fluids. These cells also participate in sensory functions as they contain nerve endings, helping the body perceive different external stimuli such as touch, temperature, and pain. Additionally, by undergoing apoptosis, keratinizing cells maintain the epithelial cell population and contribute to the formation of a unique environment for microorganisms, contributing to healthy skin microbiota. This complex interplay of functions makes keratinizing barrier epithelial cells critical to homeostasis and overall body health." DOI:10.1111/j.1469-7580.2009.01066.x|DOI:10.4103/jomfp.JOMFP_195_16|DOI:10.1111/j.0022-202X.2004.23213.x|DOI:10.1016/j.jaci.2016.09.019 +635 CL:0000228 CL_0000228 "A multinucleate cell is a type of cell containing multiple nuclei. These cells develop primarily through two cellular processes: karyokinesis without cytokinesis or through cell fusion. In the former scenario, the nuclear division (mitosis) occurs without further division into separate cells (cytokinesis). The latter case is when multiple cells fuse together, generating a cell with multiple nuclei. These cells can be observed in several types of tissues within various organisms and play a significant role in biological systems. + +Multinucleate cells have specific functions depending on their tissue origin. For instance, multinucleate cells can be found in the human skeletal muscle in the form of skeletal muscle fibers or myotubes. They are formed through fusion of individual muscle cells called myoblasts, conferring distinct functional advantages for the maintenance and repair of tissues. The multiple nuclei provide an increased DNA template, allowing for efficient production of the proteins such as actin and myosin needed for muscle contraction. Consequently, these multinucleate muscle fibers can be longer and have a larger volume than typical cells, contributing to muscle efficiency and strength. + +Multinucleate cells can also be found in the immune system, specifically in a subtype of macrophages that undergo fusion. An example is the multinuclear osteoclast, a particular type of multinucleate cell responsible for the reabsorption of bone tissue during bone growth, development, and repair. Multinucleated giant cells, a subtype of macrophages, are formed by the fusion of several macrophages when they encounter foreign substances too large for single cell phagocytosis. These giant cells have a central role in combating larger foreign substances, such as parasitic worms and implanted medical devices. The formation and function of multinucleate cells is extremely diverse, indicating their essential role in various biological contexts, from muscle function to immunity." DOI:10.1159/000075028|DOI:10.1242/dev.151035|DOI:10.1242/jcs.216267|DOI:10.1016/j.ajpath.2019.02.006 +636 CL:0000306 CL_0000306 "Crystallin accumulating cells, as their name suggests, predominantly play a pivotal role in the accumulation of a group of water-soluble proteins known as crystallins, within cellular structures. This cell type is typically found in the ocular lens, contributing significantly to its main function of focusing light onto the retina, enabling vision. The proteins these cells gather and store directly facilitate lens transparency and refractive index — two crucial elements in the light-focusing process. + +The function and importance of crystallin accumulating cells stem from the very proteins they collect. Crystallin proteins have a high solubility and an ordered, compact, globular structure, which allows them to densely pack within these cells, thereby minimizing light scattering and maximizing transparency. These proteins are divided into three types: alpha, beta, and gamma crystallins. Their different organizational structure and interaction contribute to optical clarity and lens resilience, and any alterations in their clustering can potentially lead to cataract formation. + +Crystallin accumulating cells are unique in their phenomenal protein gathering capability and longevity. Unlike most cells in the body, the lens cells, including the crystallin accumulating cells, do not undergo regular turnover, remaining in the lens throughout an individual's lifespan. As a consequence, an optimal functionality and homeostasis maintenance of these cells are crucial for lens transparency over time. " DOI:10.1016/j.preteyeres.2006.10.003|DOI:10.1016/j.pbiomolbio.2014.02.006|DOI:10.1038/s41594-020-00543-9|DOI:10.1016/j.pbiomolbio.2014.05.002|DOI:10.1186/1479-7364-6-26 +637 CL:0000313 CL_0000313 "Serous secreting cells are specialized types of epithelial cells primarily involved in the production and release of serous secretions. Known for their high content of proteins, these cells can be found in the trachea, bronchus, bronchioles, and submucosal glands. They are most notably found in the salivary glands, where they produce digestive enzymes such as amylase. + +These cells are typically characterized by a relatively round shape and a basally located spherical nucleus. The cytoplasm is densely packed with well-developed rough endoplasmic reticula and numerous zymogen granules, reflective of their active role in protein synthesis and secretion. This substantive cellular machinery is designed explicitly for producing copious amounts of serous secretions, which are pivotal to respiratory, digestive, and other bodily functions. + +On a functional level, the secretions of serous cells are employed in two main capacities: digestion and protection. In the digestive system, serous cells contribute to macromolecular breakdown, primarily of carbohydrates through the enzyme amylase. This function is critical to the overall process of digestion and absorption of nutrients in the body. On the other hand, the watery secretions play a protective role, aiding in the continuous moistening and lubrication of the body's internal surfaces and organ linings against bacterial invasion and mechanical stress. Hence, serous secreting cells form an integral part of our daily physiological functions while playing an underappreciated role in maintaining health and bodily homeostasis. + + +" DOI:10.1146/annurev.ph.52.030190.000525|DOI:10.1152/ajplung.1994.267.2.L206|DOI:10.1183/09031936.93.06040498|DOI:10.1002/jemt.1070260104 +638 CL:0000307 CL_0000307 "Tracheal epithelial cells, also known as bronchial epithelial cells, are specialized cells that form the lining of the trachea, a crucial part of the respiratory system. They form a continuous layer known as the epithelium, which serves as the first line of defense against airborne pathogens and particles. These cells play a significant role in keeping the respiratory system healthy and functional. + +Tracheal epithelial cells are equipped with cilia, tiny hair-like projections that move in coordinated waves. This ciliary movement, along with the mucus produced by these cells, forms an essential barrier, known as the mucociliary escalator, that traps and moves foreign particles, harmful microorganisms, and debris up and out of the lungs. Beyond defense, these cells also help in maintaining the humidity and temperature of the air entering the lungs, ensuring optimal conditions for gas exchange. + +Pathologically, tracheal epithelial cells are involved in various respiratory diseases. The dysfunction or damage of these cells can lead to conditions such as chronic obstructive pulmonary disease (COPD), asthma, bronchitis, or cystic fibrosis. In cystic fibrosis, a change in the genetic information of these cells can cause abnormally thick and sticky mucus, leading to a breakdown of the protective mucociliary escalator and resulting in recurrent, severe lung infections." DOI:10.1038/s41577-020-00477-9|DOI:10.1038/s41385-020-00370-7|DOI:10.1038/mi.2017.71|DOI:10.1007/BF00234174|DOI:10.1513/pats.200605-117SF +639 CL:0000323 CL_0000323 "A lysozyme secreting cell is a specific type of cell primarily involved in the synthesis and secretion of the enzyme lysozyme, a crucial component in our body's defense mechanism against microbial invasion. These cells are mainly found in various tissues throughout the body, including the mucosal lining of the respiratory and digestive tract, tears, saliva, and human milk, along with some specific immune cells. + +Functionally, lysozyme secreting cells play a crucial role in innate immunity, due to the antimicrobial action of lysozyme. The enzyme is capable of degrading the peptidoglycan layer of bacterial cell walls, which results in the lysis and destruction of the bacteria. This antimicrobial mechanism acts as one of the first-line defenses against pathogenic microbes, even before the adaptive immune response is triggered. Therefore, lysozyme-secreting cells play a pivotal role in maintaining the body's health by creating a hostile environment for potential invaders. + +Under abnormal circumstances, the functionality of these cells can significantly contribute to the progression of certain diseases. For instance, overproduction of lysozyme due to increased activity of lysozyme secreting cells may lead to the development of inflammatory diseases like arthritis. In contrast, deficiencies in lysozyme production can expose the body to increased risk of bacterial infections. Thus, the balance of lysozyme secreting cell activity is critical for its normal antimicrobial function in the body." DOI:10.3390/antibiotics10121534|DOI:10.1126/science.aal4677|DOI:10.1165/rcmb.2011-0011RT|DOI:10.3389/fimmu.2020.00427/full +640 CL:0000311 CL_0000311 "Keratin-accumulating cells, primarily known as keratinocytes, are a distinctive type of epithelial cells predominantly found in the skin's outermost layer known as the epidermis. These cells are responsible for the production of a unique type of protein called keratin. Keratin is a crucial part of the biological structure and functionality of these cells and is essential in creating a protective barrier for the body. These cells form a protective shield against environmental damage such as UV radiation, harmful microbes, and physical injuries. + +The primary function of keratinocytes is the synthesis and accumulation of keratin, which undergoes minor modifications such as desquamation and cornification resulting in the formation of a solid and stable protein-rich protective layer on the body's surface. The production of keratin is a highly coordinated and regulated process. The cytoskeleton of these cells is primarily composed of keratin intermediate filaments. During keratinocyte maturation and differentiation, keratin-accumulating cells transit from the basal layer to the outermost layer of the skin during which they synthesize different types of keratins sequentially creating a stratified and structured epidermal layer. + +Moreover, keratinocytes produce cytokines and chemokines that have defensive roles against pathogenic intruders. Additionally, these cells partake in the inflammation process by signaling immune cells to the area of the injury. Furthermore, keratinocytes play crucial roles in wound healing and skin regeneration. In addition to having a protective and barrier-centric role, keratinocytes are also involved in regulating the rate of water loss from the body, maintaining body temperature, and facilitating sensory perception. " DOI:10.1007/s00418-008-0435-6|DOI:10.1083/jcb.201404147|DOI:10.1016/j.bbamcr.2013.06.010|DOI:10.1172/jci.insight.142067|DOI:10.3390/ijms21228790 +641 CL:0000319 CL_0000319 "Mucus secreting cells are specialized epithelial cells that are widely distributed throughout the body. They can be found predominantly in the respiratory and gastrointestinal tracts, more specifically in the lining of the nose, lungs, stomach, intestines, and the surface of eyes. Most mucus secreting cells have a distinctive goblet-like shape that is attributed to their dense accumulation of secretory vesicles and are considered goblet cells. + +The primary function of mucus secreting cells is the production and release of mucus, a gel-like substance composed mainly of glycoproteins known as mucins. Mucus serves several crucial functions in the body, from protecting the epithelial cells of the body's vital organs against abrasive damage, to trapping foreign bodies, such as dust and bacteria, thereby playing a key role in the innate immune system. It also keeps the epithelial tissues hydrated and lubricated, enabling smooth movement of various substances and preventing drying out of tissues. + +The secretion of mucus by mucus secreting cells is a complex process and its dysregulation can lead to disease. Mucins are synthesized within the endoplasmic reticulum and the Golgi apparatus of the cell. When stimulated, the mucus secreting cells release the mucus by exocytosis, a process involving the fusion of the secretory vesicle membrane with the cell's plasma membrane. This action is often in response to both chemical and mechanical stimuli. However, abnormal function of mucus secreting cells can lead to certain diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD)." DOI:10.1016/j.chest.2017.11.008|DOI:10.1172/JCI15217|DOI:10.1016/j.addr.2017.09.023|DOI:10.1038/mi.2015.32|DOI:10.1080/01926230601060025 +642 CL:0000327 CL_0000327 "Extracellular matrix secreting cells are responsible for the production, secretion, and organization of the extracellular matrix (ECM). The ECM is a complex network of proteins and polysaccharides secreted by cells that provides structural and biochemical support to the surrounding cells. It plays a crucial role in tissue and organ morphogenesis, in the differentiation of tissues, and in normal and abnormal cellular functions. Several types of ECM secreting cells exist in the body, including chondrocytes, which secrete collagen and glycosaminoglycans. + +Originating from the early stages of embryonic development, ECM secreting cells undergo a maturation process where changes in gene expression allow them to specialize in ECM production. Importantly, cell-ECM interactions are critical for tissue structure and function. They mediate cell adhesion, cell-to-cell communication, and differentiation, impacting tissue integrity and functionality. The ECM is a dynamic and intricate network subject to continuous remodeling and turnover throughout the lifespan of an organism. + +Anomalies in ECM cells or the secreted ECM can lead to a variety of pathological conditions. For instance, excessive ECM secretion may result in tissue fibrosis, while insufficient secretion can lead to tissue degeneration disorders, such as osteoarthrosis. In cancer, changes in ECM can also contribute to tumor growth and metastasis. Thus, the normal biology of ECM secreting cells and their regulatory mechanisms is key for maintaining a healthy state in the body. +" DOI:10.1242/jcs.023820|DOI:10.1016/j.joca.2017.02.797|DOI:10.1016/bs.ctdb.2018.03.006|DOI:10.1242/dev.175596|DOI:10.1242/dmm.004077 +643 CL:0000329 CL_0000329 "Oxygen-accumulating cells possess the distinctive ability to store or accumulate oxygen in its surroundings. Such cells are found in organisms that dwell in areas with fluctuating oxygen levels or require a reserve during periods of intense activity. The function of these cells primarily revolves around their capacity to absorb, store, and efficiently utilize oxygen to support various physiological processes. Erythrocytes or red blood cells as well as muscle cells are oxygen-accumulating cells. + +These cells are notable for their exceptional adaptations allowing for the high-capacity storage of oxygen. One such adaptation can be seen in the presence of oxygen-binding proteins such as myoglobin found in high concentrations in muscle cells. Myoglobin, similar to hemoglobin found in red blood cells, has a high affinity for oxygen and acts as an oxygen reserve by binding to oxygen molecules when concentrations are high, and then releasing these molecules when oxygen levels decrease in muscle cells. This crucial function helps to ensure that these cells can continue to function and support the organism's metabolism, particularly under conditions of oxygen scarcity." DOI:10.1242/jeb.043075|DOI:10.1242/jeb.023697|DOI:10.3389/fphys.2013.00332|https://www.ncbi.nlm.nih.gov/books/NBK54103/ +644 CL:0000325 CL_0000325 "The term ""stuff accumulating cells"" refers to a class of cells encompassing a variety of cell types that are characterized by their capacity to accumulate various substances. These substances can range from lipids, proteins, carbohydrates to foreign bodies which the body needs to remove. The different cell types fulfill a huge variety of functions in various tissues under normal or pathological conditions. + +Several cell types fall under this class of cell, including adipocytes, crystallin accumulating cells, keratinocytes, phagocytes, metal ion accumulating cells, pigment cells, and many more. Many 'stuff accumulating cells' function within the body's self-maintenance and repair systems by collecting and holding waste material or excess nutrients until they can be appropriately discarded or utilized. + +One key function of cells in this class is in lipid metabolism. Upon consuming food, the excess lipids that are not instantaneously needed by the body are accumulated in specialized adipocytes or fat cells. Their unique ability to adjust and increase in size allows for the safe storage of lipids without causing significant cellular damage. This accumulation aids not only for energy storage but also to prevent excess lipids from freely circulating in the body. + +Another example of a 'stuff accumulating cell' is a pigment cell, whose primary function is the synthesis and storage of melanin which is packaged into small vesicles called melanosomes, which are then transported along the cellular projections to keratinocytes. " DOI:10.1016/j.cbi.2017.12.021|https://ohiostate.pressbooks.pub/vethisto/chapter/1-cell-inclusions/ +645 CL:0000349 CL_0000349 "Extraembryonic cells are a group of different cell types that emerge during the early stages of embryonic development. These cells play a vital part in forming the extraembryonic structures that support the growth and development of the embryo, including the placenta, yolk sac, allantois, and chorion. Although they don't contribute to the baby's constitution, extraembryonic cells play a vital role in ensuring the embryo's survival and development during pregnancy. + +A primary function of these cells is to facilitate oxygen and nutrient transfer from the mother to the fetus. Notably, certain extraembryonic cells develop into the placenta, an organ in the uterus filtering oxygen and nutrients from the mother's blood to transport to the fetus. The placenta also removes waste from the fetus's blood, maintaining a stable internal environment. + +Moreover, extraembryonic cells contribute to embryo protection. Some evolve into the amniotic sac or amnion, a fluid-filled protective layer that cushions the growing embryo, mitigating pressure or potential impacts. Additionally, these cells are essential for hormone production critical to fetal development and maintaining pregnancy. Specifically, placental syncytiotrophoblast cells secrete human chorionic gonadotropin, regulating progesterone levels and supporting pregnancy continuation. " DOI:10.1098/rstb.2021.0255|https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/extraembryonic-membranes|DOI:10.1111/rda.12633|DOI:10.1098/rstb.2021.0250 +646 CL:0000386 CL_0000386 "Tendon cells are specialized muscle attachment cells that are part of the epidermal cell layer. Tendons are tough, flexible connective tissues that connect muscles to bones, transmitting the force generated by muscle contractions to allow joint movement. + +These cells play a crucial role in the synthesis and organization of the extracellular matrix within tendons, which mainly consists of collagen fibers, proteoglycans, and other matrix proteins. Through their synthesis of collagen, particularly type I collagen, tendon cells contribute to the tensile strength and resilience of tendons, enabling them to withstand mechanical forces during movement and physical activity. + +Furthermore, tendon cells interact with various signaling molecules and growth factors to regulate processes such as cell proliferation, differentiation, and inflammation within the tendon microenvironment. Overall, tendon cells play a vital role in maintaining the structural and functional integrity of tendons, making them essential for musculoskeletal health and mobility." DOI:10.1242/dev.057885|https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/tendon-cell|DOI:10.1302/2046-3758.118.BJR-2021-0576.R1 +647 CL:0000393 CL_0000393 "Electrically responsive cells refer to a subset of cells that possess the ability to respond to electrical stimuli. These cells are typically characterized by their excitable membranes, which enables them to perform critical functions in the body. They are involved in the process of signal transmission in the nervous system as neurons, and play a role in muscle contraction as muscle cells. These cells exhibit a dynamic functionality that is central to maintaining physiological homeostasis. + +At the core of their functionality is the ability to generate and propagate action potentials, a predominant type of electrical signal within the biological systems. The responsiveness to electrical stimuli is driven by the presence of voltage-gated ion channels on the membrane of these cells. These channels allow the flow of ions such as sodium, potassium, and calcium, following fluctuations in the surrounding electrical environment, which results in the creation of action potentials. Through these action potentials, information is rapidly conducted over long cellular distances, enabling efficient communication between cells and quick responses to the myriad of biological stimuli. Electrically responsive cells play a pivotal role in maintaining biological functions on multiple fronts, facilitating not just neural communication and processes, but also contributing to muscle function." DOI:10.1038/nrn2148|DOI:10.1101/cshperspect.a006023|DOI:10.1113/JP270909 +648 CL:0000388 CL_0000388 "Tendon cells are specialized elongated fibroblasts that are predominantly found in tendons, the fibrous connective tissue that connects muscle to bone. These cells are biologically unique and essential for the formation and repair of tendons. Tendon cells possess elongated cell bodies and have a spindle or stellate-like shape with thin and long cytoplasmic extensions. They are predominantly positioned longitudinally along the collagen fibers. Their primary function is to produce and maintain the extracellular matrix of tendons, which comprises primarily of collagen, proteoglycans, and other non-collagenous proteins. + +Tendon cells are actively involved in tendon homeostasis and adaptation to mechanical loading. When tendons are regularly subjected to mechanical strain, these cells react by synthesizing more matrix proteins, thus strengthening the tendon structure. In response to tendon injury or degenerative changes, tendon cells can proliferate and increase their matrix synthesis to repair and regenerate the damaged tissue. However, excessive mechanical loading or aging can result in abnormal responses, leading to pathologic changes in tendon structure and function. + +In addition, tendon cells also have immunomodulatory functions. They can orchestrate local immune responses by producing a variety of cytokines and chemokines, and by interacting with immune cells that infiltrate the tendon tissue under pathologic conditions. Moreover, tendon cells are capable of expressing genes related to nociception and have a potential role in tendon pain mechanisms." DOI:10.1038/nrrheum.2015.26|DOI:10.1016/j.jbiomech.2005.05.011|DOI:10.1152/physrev.00031.2003|DOI:10.3390/cells11030434|DOI:10.1515/sjpain-2022-0018/html +649 CL:0000404 CL_0000404 "The electrically signaling cell is a specialized cell type that uses bioelectrical signals to transmit information across the cell and between other cells in the body. These cells play an indispensable role in a multitude of physiological functions including the conduction of nerve impulses, muscle contraction, secretion, and response to external stimuli. The primary mechanism facilitating this unique capability is the generation and propagation of action potentials, transient alterations in the electrical potential difference across the plasma membrane. + +In the human body, electrically signaling cells are most commonly found in the nervous system, specifically in neurons. In neurons, the transmission of electrical signals is fundamental for the processing of sensory input, motor control, cognition, learning and memory. Neurons utilize their dendrites to receive incoming messages, their soma or cell body to process these signals, and their axons to relay the processed information to other neurons, muscles, or glands. + +The ability to generate these electrical signals involves voltage-gated ion channels and pumps found in the cell membrane of these electrically signaling cells. These channels allow the selective passage of ions including sodium, potassium, calcium, and chloride. By varying the concentrations of these ions across the membrane, they effectively modulate the membrane potential, and hence, the cell's electrical signal. The careful orchestration of these channels and pumps' activities enables these cells to rapidly alter their membrane potential, create action potentials, and ultimately facilitate rapid communication within and between cells. Abnormalities in these cells can lead to a variety of pathological conditions such as neurodegenerative diseases. +" https://www.ncbi.nlm.nih.gov/books/NBK441977/|DOI:10.1080/01677060802610604|DOI:10.1016/j.conb.2004.08.012|DOI:10.1146/annurev.physiol.66.032102.113328|DOI:10.1038/ng1758 +650 CL:0000412 CL_0000412 "A polyploid cell is a unique type of cell characterized by the possession of more than two sets of chromosomes. This is much higher than the typical diploid nature of other somatic cells. This cellular phenomenon known as polyploidy results from errors during cell division leading to the generation of non-standard polyploid cells, a property that is common to both plant and animal cells. These cells occur naturally and can also be formed through genetic manipulation. + +Polyploid cells play a critical role in the overall growth and development of organisms. In plant cells, polyploidy often contributes to speciation and diversity. A notable characteristic of many plant species is their ability to tolerate polyploidy, a trait that often leads to increased cell size, altered gene expression, and may enhance the physiological and adaptive traits of a plant. In animals, polyploidy is less common but still plays a significant role in liver function and injury repair. Polyploidization in hepatocytes aids in maintaining genetic stability and also allows for cellular adaptation to liver injury. + +Polyploid cells also play a potential role in cancer development. Some cancer cells are polyploid or aneuploid (having an abnormal number of chromosomes) indicating a relationship between chromosome status and cancer progression. Polyploidy in cancer cells may contribute to increased mutation rates, adaptation to adverse environments, and resistance to chemotherapy. Overall, polyploid cells may lead to pathological conditions like cancer, however, many are part of normal healthy biological systems, playing an integral role in the diversity and evolution of life." DOI:10.1016/j.tcb.2013.06.002|DOI:10.1016/j.tig.2015.03.011|DOI:10.1038/cddis.2017.167|DOI:10.1038/nrm1276|DOI:10.1146/annurev-cellbio-092910-154234 +651 CL:0000417 CL_0000417 "Endopolyploid cells are a specialized cell type characterized by having multiple complete sets of chromosomes, far exceeding the amount found in typical diploid cells. The process known as endoreplication results in variant cycles of DNA replication without subsequent cell divisions, leading to an increase in cell volume, an alteration in gene expression, and polyploidy. These cells are commonly found throughout the plant and animal kingdoms, indicating their foundational role in organismal biology. + +Endopolyploid cells serve critical roles in maintaining an organism's biological system by regulating tissue growth and development, cellular differentiation, and physiological response to environmental stimuli. For instance, in plants, endopolyploidy serves as a mechanism for increased cell size leading to larger fruits and broader leaves. In animals, these cells are fundamental in liver regeneration. Therefore, their prominence in adaptive and developmental processes across diverse organisms reflects their evolutionary importance. + +Endopolyploid cells also play a role in pathological conditions, primarily cancer development, where endoreplication can lead to genomic instability resulting in malignant progression. However, these cells also possess inherent potential for therapeutic applications. For example, stimulating endoreplication in cancer cells can trigger senescence and reduction in tumor growth. Furthermore, endopolyploid cells can be harnessed for regenerative medicine purposes, as they have demonstrated potential for differentiation and tissue repair. +" DOI:10.1101/gad.1829209|DOI:10.1016/j.tcb.2018.02.006|DOI:10.1038/s41418-017-0040-0|DOI:10.1016/j.cellbi.2005.10.013|DOI:10.1242/dev.080531 +652 CL:0000413 CL_0000413 "A haploid cell is a unique class of cell characterized by having a single set of chromosomes. The formation of haploid cells occurs through meiosis, a process where a diploid cell, containing two sets of chromosomes, undergoes division, resulting in four haploid cells. + +Haploid cells play an important role in the sexual reproduction of various organisms. Serving as gametes, they transmit genetic information to successive generations, contributing to genetic diversity. Their single set of chromosomes results in unique trait combinations in offspring, enhancing adaptability to changing environments. Furthermore, haploid cells facilitate the study of recessive traits in genetic research, as each gene is present in a single copy, without the influence of a dominant gene. + +It's important to note that certain organisms, such as some fungi and algae, follow a haploid dominant life cycle, spending the majority of their life cycle in the haploid phase. This phase accelerates the generation of genetic diversity among offspring, proving advantageous in rapidly changing environments. + + + + + + +" https://www.ncbi.nlm.nih.gov/books/NBK26840/|DOI:10.1186/s13287-017-0657-4|https://bccampusbiology.pressbooks.tru.ca/chapter/sexual-reproduction/ +653 CL:0000424 CL_0000424 "Excretory cells are specialized components of an organism's excretory system, responsible for eliminating waste. These cells play a crucial role in filtering blood, extracting waste, and producing urine for expulsion. However, the specifics of excretion functions may vary across different organisms and excretory cell subtypes. + +In mammals, excretory cells are prominent in structures like the kidneys, forming part of nephrons. Nephrons consist of various excretory cells, including podocytes, proximal, and distal convoluted tubule cells, collaborating to filter metabolic waste and regulate urine composition. + +In simpler organisms like flatworms and nematodes, excretory cells, known as flame cells or nephridiocytes, remove waste through tubes and ducts. Regardless of complexity, the primary roles of excretory cells across organisms are the extraction, transformation, and expulsion of waste, promoting internal homeostasis and systemic health. + + + + + +" https://www.sciencedirect.com/topics/medicine-and-dentistry/excretory-system|DOI:10.1371/journal.pone.0014754|DOI:10.1002/cphy.c140002 +654 CL:0000447 CL_0000447 "Carbohydrate secreting cells are specialized cells that are involved in the synthesis and secretion of carbohydrates. These types of cells can be found in various organisms and also diverse tissue types, including specific cells like chondrocytes, which secrete the carbohydrate glycosaminoglycan. The carbohydrates they produce often serve as key components of mucus, enzymes, and other essential biological substances. + +These cells play vital roles in the metabolism and overall health of an organism. Aside from their roles in metabolism, these carbohydrate-laden compounds have other important roles. They participate in various biological processes such as cell communication, immune response, pathogen recognition, as well as growth and development of the organism. + +Aberrations in carbohydrate secreting cells can lead to various health problems. For instance, disturbances in the pancreatic carbohydrate secretion can result in conditions such as cystic fibrosis or chronic pancreatitis. In the gut, disruption in the balance of carbohydrate production impacts the mucus lining and could potentially cause gastrointestinal disorders. This highlights the importance of such cells, both in maintaining normal physiological functions, as well as potentially playing key roles in certain pathological conditions. +" DOI:10.1002/term.2398|DOI:10.1021/ar030138x|DOI:10.1111/brv.12034|DOI:10.1023/A:1020867221861 +655 CL:0000457 CL_0000457 "Biogenic amine secreting cells are specialized types of cells found in numerous tissues and organ systems throughout the body. These cells are responsible for the synthesis, accumulation, and release of biogenic amines, a class of naturally occurring compounds derived from amino acids that play crucial roles in signal transduction. Notably, many biogenic amines function as neurotransmitters, chemicals that transmit signals across a nerve synapse, or as hormones, substances that regulate the activities of cells or organs. + +There exist several types of biogenic amine secreting cells, distinguished by the specific biogenic amines they produce and secrete. Some examples include serotonergic neurons in the brain that generate serotonin, a critical neurotransmitter involved in mood, sleep, and other functions. In the stomach, enterochromaffin-like cells secrete histamine, playing a key role in gastric acid secretion. Lastly, adrenal medulla chromaffin cells release adrenaline and noradrenaline, hormones essential for the body's fight-or-flight response. + +In general, these cells produce biogenic amines through decarboxylation, a biochemical reaction that removes a carboxyl group from amino acids. Once synthesized, the biogenic amines are stored in vesicles within the cell until an appropriate signal prompts their release. Depending upon their locations and the respective biogenic amines they secrete, the activation of these cells influences diverse physiological processes, ranging from neurotransmission and endocrine control to immune response and gastrointestinal regulation. Consequently, abnormal functioning of biogenic amine secreting cells is implicated in a plethora of health conditions, including neurodegenerative disorders, neuropsychiatric illnesses, cardiovascular diseases, and cancer." DOI:10.1038/nrneurol.2015.172|DOI:10.1016/S0959-4388(00)00088-X|DOI:10.3390/genes14020263 +656 CL:0000473 CL_0000473 "Defensive cells, commonly known as immune cells, play a crucial role in protecting against foreign substances and pathogens. These cells include alarm substance cells, follicular dendritic cells, M cells of gut, and phagocytes. + +Alarm substance cells are specialized cells found in certain aquatic organisms such as fishes and are responsible for releasing chemical signals into the surrounding environment in response to perceived threats. Exposure to skin-penetrating pathogens like Saprolegnia ferax and Saprolegnia parasitica, as well as skin-penetrating parasites such as larval trematodes like Teleorchis sp. and Uvulifer sp., stimulates the production of alarm cells. + +Follicular dendritic cells are primarily found in the germinal centers of lymphoid follicles, where they play essential roles in antigen presentation and the regulation of B cell responses. On the other hand, M or microfold cells are pivotal in the surveillance of mucosal immunity, actively transporting external antigens from the gut lumen into the lymphoid follicle. + +Neutrophils and monocytes, known as phagocytes, are integral to immune responses from their early to late stages. They circulate and traverse tissues, primarily tasked with engulfing and eliminating microbes and cellular debris." DOI:10.1098/rspb.2007.0709|DOI:10.1016/j.celrep.2019.10.086|DOI:10.1186/s41232-018-0072-y|https://www.sciencedirect.com/topics/immunology-and-microbiology/phagocyte +657 CL:0000458 CL_0000458 "Serotonin secreting cells are a type of biogenic amine secreting cell that can be found in the gastrointestinal tract and in the lungs. These cells are among the most prevalent enteroendocrine cell types scattered throughout the gastrointestinal mucosa. The majority of the body's serotonin (around 90%) is produced in the gut by these serotonin secreting cells. They produce and secrete serotonin (5-hydroxytryptamine, 5-HT), a vital signaling molecule that impacts a range of physiological activities. + +Primarily, these serotonin secreting cells contribute to the regulation of gut motility, secretion, visceral sensitivity, and local blood flow. In response to chemical, mechanical, or hormonal changes within the lumen of the gut, these cells produce and secrete serotonin. For example, they detect and respond to the presence and movement of food, playing an important regulatory role in digestion. The secretion of serotonin initiates peristaltic and secretory reflexes, aiding in the movement and processing of food within the gut. + +In addition, serotonin secreting cells play a crucial role beyond the gastrointestinal tract. Serotonin is also a vital neurotransmitter in the brain and contributes to feelings of wellbeing and happiness. A lack of serotonin is often associated with mood disorders, such as depression and anxiety. Thus, these cells play a crucial role both in the local control of the gastrointestinal system and in the wider systemic and neurological functions of the body." DOI:10.1038/nrgastro.2013.105|DOI:10.1152/ajplung.00167.2005|DOI:10.1038/nrgastro.2017.51|DOI:10.1016/j.lfs.2018.08.050|DOI:10.1016/j.ejphar.2014.10.031 +658 CL:0000500 CL_0000500 "Follicular epithelial cells are associated with oocytes in the ovarian follicles. These follicular epithelial cells surround and support the developing oocyte, with both cells types contributing to bi-directional signaling to promote oocyte and follicular development and maturation. + +Throughout the development of the follicle, the follicular epithelial cells support the oocyte and proliferate. In primordial follicles, the oocyte is surrounded by single layer of ovarian follicular epithelial cells called pre-granulosa cells. Upon hormonal activation, the follicle develops into a primary follicle containing the oocyte surrounded by a single layer of granulosa cells. At the secondary follicle stage, the granulosa cells proliferate and form multiple layers, eventually sub-specializing into cumulus granulosa cells, which continue to surround the oocyte, and mural granulosa cells, which line the follicular wall and form a stratified epithelial layer. + +Follicular epithelial cells appear to play important roles in oocyte development, fertilization, early embryonic development, and pregnancy. Additionally, ovarian tumors may also arise from granulosa cells. These cells are crucial for the normal functioning of the female reproductive system." DOI:10.1016/j.anireprosci.2004.05.017|DOI:10.1016/j.fertnstert.2014.11.015|DOI:10.3390/cells10092292|DOI:10.1016/B978-0-12-813209-8.00002-9|DOI:10.3389/fphys.2021.800739 +659 CL:0000506 CL_0000506 "Enkephalin secreting cells are a subpopulation of endrophine secreting cells that are primarily involved with modulating pain perception, stress responses, and reinforcement mechanisms. These distinctive cells synthesize and secrete enkephalins, a type of endogenous opioid peptide. Enkephalins are crucial regulators of pain perception, with their primary role being to decrease the experience or sensation of pain. They work by binding to specific opioid receptors present on the surface of certain neurons, thus attenuating the transmission of pain signals to the brain. + +These cells are widely distributed in both the central and peripheral nervous systems, with a significant concentration in regions of the brain. Peripherally, enkephalin secreting cells are also located in the adrenal medulla, as well as pain-responsive and inflammation-related areas including the dorsal root ganglia and the intestinal tract. Reflecting their broad functional roles, these cells not only serve as key actors in pain modulation but also in physiological processes like mood regulation, reward behavior, stress responses, and immune response. + +In addition to their involvement in stress modulation and pain control, enkephalin secreting cells also play a vital role in maintaining homeostasis and regulating various physiological responses. For instance, in the context of physical threat or stress, these cells increase the release of enkephalins, causing a surge in pain tolerance, and offering potential survival benefits. Experimental studies suggest that abnormalities or dysfunctions in enkephalin secreting cells or the broader enkephalin system may be related to various health conditions, such as chronic pain disorders, opioid addiction, mood disorders, and various forms of stress-related illness." DOI:10.3389/fnsys.2022.932546|DOI:10.1155/2017/1546125|DOI:10.1016/bs.vh.2019.05.001|https://www.ncbi.nlm.nih.gov/books/NBK557764/ +660 CL:0000507 CL_0000507 "Endorphin secreting cells are specialized cells thatproduce and release endorphins. Endorphins are a type of neurotransmitters, generated in response to stress and pain, which function to limit the transmission of pain signals and evoke feelings of pleasure or euphoria. These cells play a key role in the biological systems related to pain perception and emotional regulation. + +Natively, endorphin secreting cells are predominantly found within the pituitary gland and hypothalamus. When the body undergoes stressful situations or encounters harm, these cells are signalled to release endorphins. The produced endorphins bind to the opioid receptors in the brain, blocking pain signals and inducing feelings of well-being. This mechanism is a critical protective response of the human body, acting to mitigate pain and discomfort. + +Aside from their chief role in pain modulation, endorphin secreting cells also contribute significantly to various physiological functions. Endorphins also interact with the reward system of the brain, which results in feelings of pleasure and positivity. This effect is marked in scenarios such as the 'runner's high', experienced during continuous, rigorous exercise. Additionally, endorphins help in modulating appetite, releasing sex hormones, and enhancing the immune response. Collectively, the functions of endorphin secreting cells underscore their key role in maintaining the balance and overall well-being of the body amidst different physical stressors." https://www.ncbi.nlm.nih.gov/books/NBK470306/|DOI:10.3390/ijms22010338|DOI:10.1093/cercor/bhn013|DOI:10.1016/S0195-6663(81)80042-6 +661 CL:0000511 CL_0000511 "The androgen binding protein (ABP) secreting cell is a highly specialized cell distinctively featured in male reproductive system, specifically known as the Sertoli cells of the testes. These cells play a pivotal role in male fertility and overall reproductive health. Classified under the epithelial cells, they are embedded within the seminiferous tubules' walls, effectively forming a crucial part of the blood-testis barrier, thus ensuring the proper partitioning of the various stages of spermatogenesis. + +ABP secreting cells are fundamentally involved in producing and secreting ABP, a glycoprotein that binds androgens such as testosterone and dihydrotestosterone. Consequently, they play a crucial role in modulating circulating testosterone levels and successfully maintaining a high concentration of male sex hormones within the seminiferous tubules. This directly influences the maturation process of sperm. + +Additionally, these cells have regulatory functions that contribute further to male fertility. They aid the process of spermiation, which is the release of mature spermatids into the lumen of the seminiferous tubules. Moreover, the secretion of ABP by these cells also reinforces the local effects of androgens on spermatogenesis. It is also known that ABP regulates the bioavailability, as well as the functional potency of intra-testicular androgens. Consequently, any abnormal function or alteration in these cells, such as producing less ABP, can contribute to male infertility. " DOI:10.1016/0303-7207(75)90021-0|DOI:10.1006/scdb.1998.0203|DOI:10.1210/me.2002-0070|DOI:10.1002/j.1939-4640.2002.tb02296.x +662 CL:0000518 CL_0000518 "Phagocytes (sensu vertebrate) are a critical component of the immune system, a diverse range of specialized cells aimed at preserving the health and integrity of an organism. The term ""phagocyte"" literally translates to ""eating cell"" and indeed, these cells are specialized in engulfing and digesting foreign particles, pathogens and dead or dying cells in a process known as phagocytosis. In the context of vertebrates, this cell type includes mononuclear phagocytes, multinucleated phagocytes, and osteoclasts. + +Mononuclear phagocytes are derived from precursor cells in the bone marrow. They encompass monocytes, macrophages, and dendritic cells, are tasked with engulfing and digesting foreign particles and pathogens, as well as presenting antigens to activate other immune cells. They are widely distributed throughout tissues and can, under certain circumstances, differentiate into multinucleated giant cells or osteoclasts. + +Osteoclasts, which are responsible for bone resorption, typically engage in bone remodeling under normal physiological conditions. However, in pathological states like rheumatoid arthritis and osteoporosis, osteoclasts contribute to bone degradation and loss. +" DOI:10.3389/fimmu.2017.00499|https://www.sciencedirect.com/topics/medicine-and-dentistry/mononuclear-phagocyte|DOI:10.1111/j.1365-2613.2000.00164.x|DOI:10.3389/fcell.2022.873226 +663 CL:0000527 CL_0000527 "An efferent neuron is a specialized type of neuron integral to the proper functioning of the nervous system and includes motor neurons. These neurons form a critical part of the pathway that delivers instructions from the brain and spinal cord towards the body's muscles and glands. This results in muscle contractions or glandular secretions which underlie our voluntary movements and automatic responses respectively. They represent the final step in a sequence of actions, transporting signals from the central nervous system outward to elicit a response. + +Efferent neurons exhibit distinct characteristics which allow them to carry out their function. They have a cell body, housing the nucleus and other essential components, and long appendages known as axons that transmit signals away from the cell body. These signals, in the form of action potentials, traverse the length of the neuron to reach nerve endings, which then release neurotransmitters. The neurotransmitters, in turn, bind to receptors on effectors such as muscles or glands, stimulating a response. Therefore, efferent neurons are vital for accurately delivering signals from our brain to various parts of our body. +" https://www.sciencedirect.com/science/article/abs/pii/S0165027097001763|DOI:10.1111/j.1460-9568.1995.tb01092.x|DOI:10.1152/jn.1994.71.2.437 +664 CL:0000540 CL_0000540 "Neurons play a significant role in the nervous system as the major components involved in the reception, processing, and transmission of information. These cells are functionally diverse and unique, but they all share basic structures including the cell body (soma), dendrites and the axon. The soma, which contains the nucleus, is the main section of the cell, whereas the dendrites, protruding from the soma, receive signals from other neurons. The axon, a long tail-like structure, transmits messages away from the soma towards other cells. + +Neurons carry out the key task of facilitating communication within the body. They receive signals through the dendrites, process these signals in the soma, and then relay the signals down the axon to the synapse, from where they are transferred to other neurons or directly to the body’s muscle or gland cells. This process is integral to the entirety of the body’s functions, including thought processing, coordination of body parts, and reaction to stimuli." https://www.ncbi.nlm.nih.gov/books/NBK441977/|DOI:10.1080/01677060802610604|DOI:10.1016/j.conb.2004.08.012|DOI:10.1016/j.ceb.2022.102133 +665 CL:0000548 CL_0000548 "Animal cells constitute the basic unit of life in organisms of the animal kingdom. Unlike plant cells, they do not have cell walls or chloroplasts, but they do have organelles, including the nucleus, the mitochondria and the endoplasmic reticulum. The nucleus governs cellular activities such as growth and reproduction, while mitochondria generate energy. The endoplasmic reticulum (ER) comprises the rough ER, involved in protein synthesis, and the smooth ER, contributing to lipid synthesis.The cytoplasm, a gel-like substance, hosts vital metabolic activities within the cell. Additional organelles, such as the Golgi apparatus, lysosomes, and peroxisomes, play roles in packaging, digestion, and detoxification, respectively. + +Unlike the fixed shape of plant cells, animal cells exhibit diverse sizes and irregular shapes due to the absence of a rigid cell wall. This structural flexibility allows for movement, crucial for cells involved in dynamic processes like the immune response. Specialized animal cells perform distinct functions, exemplified by neurons transmitting signals, red blood cells delivering oxygen, and muscle cells enabling body movements. Collectively, the diverse functions of animal cells contribute to the intricate processes sustaining the complexity of the animal organism." https://www.ncbi.nlm.nih.gov/books/NBK9841/|https://www.ncbi.nlm.nih.gov/books/NBK26841/|https://www.ncbi.nlm.nih.gov/books/NBK9953/ +666 CL:0000547 CL_0000547 "The proerythroblast, also know as rubriblast or pronormoblast, is a pivotal component in the hematopoietic lineage as it initiates the sequence of erythrocyte development. It is primarily sourced from hematopoietic stem cells in bone marrow through the process known as erythropoiesis. This complex process is driven by a series of intricate genetic regulations, growth factors, and hormonal cues such as erythropoietin, a vital hormone regulating red blood cell production. + +Morphologically, proerythroblasts are larger than mature erythrocytes and exhibit a basophilic cytoplasm brought about by the high concentration of ribosomes. The nucleus, round with prominent nucleoli, occupies the central cytoplasm, signifying high proliferative activity. + +Functionally, the proerythroblast is vital for hemoglobin biosynthesis and cell morphology transformation. It undergoes proliferation and differentiation stages to form erythroblasts, culminating in the release of a reticulocyte into the bloodstream as a mature red blood cell. As the starting point of red blood cell production, the proerythroblast significantly contributes to the body's overall oxygen-carrying capacity." https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/proerythroblast|DOI:10.1007/s12551-019-00579-2 +667 CL:0000568 CL_0000568 "Amine Precursor Uptake and Decarboxylation Cells (APUD cells) are primarily found in the gastrointestinal tract and respiratory system. APUD cells vary in their morphology and their exact function is determined by their location in the body. + +In the endocrine system, APUD cells have a central role in producing a diverse array of substances, including hormones (e.g., insulin, glucagon), peptides (e.g., gastric inhibitory peptide, somatostatin), and neurotransmitters (e.g., serotonin, catecholamines, histamine). These compounds are vital for regulating key physiological responses such as digestion, glucose metabolism, and bronchial relaxation. The cells achieve this regulatory function by adeptly sensing environmental changes, such as variations in nutrient availability, and promptly secreting the specific hormone required in response. + +In relation to disease, abnormalities in APUD cells can lead to multiple disorders. These include Cushing's syndrome, stemming from excessive adrenocorticotropic hormone (ACTH) production, Zollinger-Ellison syndrome caused by gastrin overproduction, and carcinoid syndrome attributed to serotonin excess. Furthermore, due to their neuroendocrine properties, pathological conditions may contribute to the development of neuroendocrine tumors." https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/apud-cell|DOI:10.1111/j.1469-7793.1997.363bn.x|DOI:10.1111/j.1469-7793.2001.0581h.x|DOI:10.1016/S0147-0272(76)80010-4 +668 CL:0000558 CL_0000558 "A reticulocyte is an immature red blood cell characterized by the remnants of ribosomal RNA in the cytoplasm, These cells, originating in the bone marrow during erythropoiesis, are transitional forms between immature and fully mature red blood cells. + +As reticulocytes mature into erythrocytes, they lose residual RNA and gain the ability to transport oxygen through hemoglobin. This transition typically takes one to two days. The percentage of reticulocytes, known as the reticulocyte count, is a key clinical marker for assessing red blood cell production in the bone marrow. + +Reticulocytes respond dynamically to abnormal red blood cell loss, as seen in conditions like autoimmune hemolytic anemia or significant blood loss. Increased demand for oxygen signals the bone marrow to boost reticulocyte production. Consequently, a higher reticulocyte count is common in such situations. Conversely, lower counts may indicate conditions where the bone marrow struggles to produce enough red blood cells, as in aplastic anemia. Therefore, reticulocytes, pivotal in erythrocyte production, also serve as a vital diagnostic tool in hematologic diseases, contributing significantly to circulatory system health. +" https://www.ncbi.nlm.nih.gov/books/NBK542172/|DOI:10.1097/MOH.0b013e328345213e|https://www.ncbi.nlm.nih.gov/books/NBK264/|DOI:10.3390/membranes12030311 +669 CL:0000578 CL_0000578 "The term ""experimentally modified cell in vitro"" encompasses cells that have been modified in a controlled experimental setting, usually within a laboratory, outside the confines of a living organism. These modifications occur using diverse techniques and tools, such as a petri dish or test tube, allowing precise control over the experimental conditions. + +The functions and characteristics of these cells can be vastly different, based on the modification or treatment they undergo. For example, cells can undergo genetic modifications to highlight specific characteristics or behaviours, or to intentionally inflict a disease state, such as cancer, for research purposes. Other modifications might include environmental stressors or treatments with different medications or compounds, aiming to observe the cells' response or resistance. Thus, although ""experimentally modified cell in vitro"" encompasses an endless variety of cells, their shared characteristic is their use as tools to investigate and elucidate the complexities of cellular function and response. + +" https://www.ncbi.nlm.nih.gov/books/NBK216047/|https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/in-vitro-studies +670 CL:0000586 CL_0000586 "Germ cells are highly specialized cells exclusively located in the gonads (ovaries in females, testes in males) and give rise to gametes. + +During early embryonic development, specific cells earmarked as germ cells undergo meiosis, reducing genetic material to a haploid state. In males, these cells become spermatozoa, while in females, they transform into oocytes or egg cells. Beyond their reproductive role, germ cells contribute significantly to genetic diversity through recombination during meiosis, creating unique genetic material. + +Germ cells are influenced by factors like age, environment, and lifestyle, directly impacting fertility, pregnancy, and offspring health. Damage or mutations at the germ cell level can lead to severe outcomes such as infertility, birth defects, or genetic disorders in offspring. " DOI:10.1038/cr.2008.116|DOI:10.1007/978-1-4614-4015-4_7|DOI:10.3390/ijms22041979|DOI:10.1016/j.mrrev.2017.04.001 +671 CL:0000593 CL_0000593 "Androgen-secreting cells are specialized cells which play a crucial role in the endocrine system, particularly in the reproductive processes of males. Their principal function is the production and release of androgens, including testosterone, dihydrotestosterone, and androstenedione. In both males and females, androgens contribute to development, sexual behaviors, and metabolic processes. In males, androgens are vital for the development of male characteristics during puberty and for maintaining male reproductive health and sexual function throughout adulthood. + +Androgen-secreting cells include theca cells, hilus cells, and type III cells of the adrenal cortex. Testosterone-secreting cells include Leydig cells of the testes and luteal cells of the corpus luteum. Theca cells of the ovary are recruited during follicular development and contribute to the complex signaling pathways required therein. Specifically, theca interna cells produce androstenedione, which can be converted by granulosa cells of the follicle to estrogens. Hilus cells, located in the hilum of the ovary, are considered to be the ovarian counterpart to Leydig cells with similar histological characteristics. Androgens are also produced by cells in the zona reticularis of the adrenal cortex. + +Malfunctions or abnormalities in androgen-secreting cells can lead to various disorders. In males, a deficiency in androgen production can cause impaired sexual development or infertility. Conversely, excessive androgen production can lead to conditions such as hirsutism or polycystic ovary syndrome in females, characterized by the presence of male-pattern hair growth and other masculinizing symptoms. Therefore, a balanced and properly regulated function of androgen-secreting cells is vital for human reproductive health." DOI:10.1007/978-3-319-31973-5_5|DOI:10.1159/000494900|DOI:10.1016/j.biocel.2005.01.016|https://www.ncbi.nlm.nih.gov/books/NBK537260/ +672 CL:0000595 CL_0000595 "The enucleate erythrocyte, commonly known as the red blood cell (RBC) or simply erythrocyte, is a vital element in the blood's cellular composition, crucial for the body's physiological processes. This unique blood cell lacks a nucleus, evident under a microscope by its distinctive biconcave disc shape, optimizing cell volume, surface area, and flexibility for circulation through the body's capillaries. While animals such as birds, reptiles, fishes, and amphibians, possess nucleated erythrocytes, most mammals have enucleate erythrocytes. + +Enucleate erythrocytes primarily function to transport oxygen from the lungs to all body tissues and organs, while simultaneously carrying waste carbon dioxide back to the lungs for expulsion. Hemoglobin, a protein within erythrocytes, binds readily to oxygen, facilitating its transport. Additionally, these cells contribute to immune responses and maintain the body's acid-base balance critical for normal bodily function. + +Erythrocyte production, termed erythropoiesis, occurs in the bone marrow. Progenitor cells undergo maturation, losing their nucleus and organelles, a unique event in human cell biology. This enucleation results in a more flexible cell with enhanced hemoglobin capacity for efficient gas transport. The typical lifespan of a human erythrocyte is approximately 120 days, after which macrophages, primarily in the spleen, remove them from circulation. Despite lacking a nucleus, enucleate erythrocytes have mechanisms to sense and adapt to environmental changes, ensuring their effective role in oxygen transportation." https://www.ncbi.nlm.nih.gov/books/NBK2263/|DOI:10.3389/fphys.2017.01076|DOI:10.3389/fphys.2021.655393|DOI:10.1152/ajpregu.00276.2020 +673 CL:0000623 CL_0000623 "Natural killer cells, often abbreviated as NK cells, are a type of cytotoxic lymphocyte critical to the innate immune system. These cells were named for their inherent ability to kill a variety of target cells without prior sensitization to them. Their primary role in the body’s immune defense mechanism is to provide rapid responses to virally infected cells while also responding to the formation of tumors. + +NK cells are unique among the immune cells due to their ability to recognize stressed cells in the absence of antibodies, allowing for a much faster immune reaction. They primarily identify and control the spread of early signs of cancer and infections by performing immunosurveillance, by scanning the body for abnormal cells. Once an infected or abnormal cell is found, NK cells activate a series of responses that lead to the destruction of the affected cells, a process called apoptosis or programmed cell death. + +Of particular note is that unlike other immune cells, the activity of NK cells is tightly regulated by a balance between inhibitory and activating signals, a critical feature in their functional response. This helps to prevent damage to normal (healthy) cells which might otherwise be targeted during an immune response. Hence, in addition to their roles in fighting tumors and infections, NK cells also contribute significantly to the immune tolerance, thereby maintaining overall body balance. " DOI:10.1038/ni1582|DOI:10.3389/fimmu.2018.01869|DOI:10.3389/fimmu.2022.879124|DOI:10.1038/cdd.2013.26|DOI:10.1073/pnas.1206322110 +674 CL:0000627 CL_0000627 "A transporting cell is a type of cell that specializes in moving molecules, nutrients, ions, and other substances across biological structures. This process is vital in multicellular organisms, regulating physiological functions and maintaining overall body balance. This cell type includes choroid plexus epithelial cells and M cells of the gut. + +Choroid plexus epithelial cells play a pivotal role in secreting cerebrospinal fluid into the brain's ventricles, establishing a crucial selective barrier between the neural system and blood. Additionally, they are the primary source of cerebrospinal fluid secretion, facilitated by specific ion channels within these cells. Furthermore, choroid plexus epithelial cells synthesize and release vital growth factors and peptides essential for the repair of the injured cerebrovascular system. + +M cells, also known as microfold cells due to their distinctive structure, are specialized epithelial cells located primarily above gut-associated lymphoid tissues (GALT) like Peyer’s patches in the ileum. Their primary role involves sampling and transporting antigens/pathogens from the luminal surface to the sub-epithelium through a process known as transcytosis. + + + +" DOI:10.3389/fnmol.2022.949231|https://www.ncbi.nlm.nih.gov/books/NBK534232 +675 CL:0000630 CL_0000630 "Supporting cells, also known as sustentacular cells, are specialized cells providing structural or physiological support to adjacent functioning cells in various bodily tissues. They contribute to the architecture and function of their respective organ systems, playing pivotal roles in maintaining integrity and optimized operation. + +In the nervous system, glial cells like astrocytes, oligodendrocytes, Schwann cells, and microglia fulfill functions such as providing nutrients, maintaining homeostasis, participating in signal transmission, and forming the myelin sheath for efficient impulse propagation. They also aid in neural repair and regeneration post-injury. + +In the sensory system, supporting cells are present in sensory epithelia. For instance, in the olfactory system, they assist in detoxification, humidification of air, and guiding odorant molecules to nerve endings. In the auditory system, supporting cells maintain the health of hair cells, crucial for sound detection and balance. In organs like the liver, these cells contribute to substance secretion and reabsorption. Despite being named supporting cells, they are dynamic and responsive, playing active roles in the cell's microenvironment across various systems." https://www.sciencedirect.com/topics/immunology-and-microbiology/sustentacular-cell|DOI:10.1016/j.semcdb.2013.03.009|https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/glial-cells|https://www.ncbi.nlm.nih.gov/books/NBK10896/ +676 CL:0000667 CL_0000667 "Collagen secreting cells are crucial for the structural integrity of various tissues and organs within the body. These cells are specialized to synthesize, secrete, and organize the extracellular matrix (ECM), which provides a supportive framework for cells and tissues. Among the many components of the ECM, collagen is the most abundant protein produced by collagen secreting cells. + +Chondrocytes are a specific type of collagen secreting cell found in cartilage, where they play a key role in maintaining structural integrity. These cells exhibit extensive functional plasticity. When cartilage is damaged, signaling pathways become activated in chondrocytes that facilitate repair. However, these cells are thought to have limited migratory potential and slow synthesis of ECM. Furthermore, defects in chondrocytes that occur through the aging process are thought to play a role in the pathogenesis of osteoarthritis. Thus, the normal function of collagen secreting cells is important for repair and homeostasis of cartilage." DOI:10.1038/s41586-019-0874-3|DOI:10.1146/annurev-cellbio-100913-013002|DOI:10.1016/j.aanat.2009.05.003|DOI:10.1016/j.actbio.2021.12.006|DOI:10.1038/nrrheum.2016.65 +677 CL:0000677 CL_0000677 "Gut absorptive cells, or enterocytes, are specialized epithelial cells in the gastrointestinal tract essential for nutrient absorption. With a columnar shape, they feature numerous microvilli on their apical surface, enhancing absorption area. Equipped with apical endosomes, they facilitate active absorption. + +Functionally, these cells primarily absorb water, dietary nutrients, ions, and vitamins processed into absorbable forms by secretions and digestive enzymes. Through active transport and passive diffusion, they absorb monosaccharides, amino acids, and lipid micelles. Absorbed molecules undergo further processing or are transported into blood or lymph for distribution. + +Apart from nutrient absorption, gut absorptive cells play a crucial role in immune homeostasis. They form a barrier against pathogens, interact with gut microbiota, and regulate signals to underlying immune cells, mediating immune responses. Impairment in their function can lead to severe malnutrition and malabsorption syndromes, underscoring their critical role in overall human health." https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/enterocyte|DOI:10.4161/gmic.19320|DOI:10.1016/j.micinf.2005.04.003 +678 CL:0000681 CL_0000681 "Radial glial cells, or radial glia, are key cells in the developing nervous system, mainly located in the ventricular zone of the developing cerebral cortex. Emerging from neuroepithelial cells early in brain development, they serve as neural stem cells and provide a scaffold for migrating neurons. + +These cells possess the ability to self-renew and generate various neurons and certain glial cells. Through symmetric and asymmetric cell divisions, they produce neurons directly or via intermediate progenitor cells, ensuring precise cell type and quantity for the complex layers of the cerebral cortex. + +In addition to their role in neurogenesis, radial glial cells act as physical scaffolds guiding neuronal migration. Their long radial processes form a pathway for newborn neurons to travel, attaching and detaching as they move along. After neurogenesis and layering, radial glial cells may transform into astrocytes or undergo apoptosis. Some may also persist in the adult brain as neural stem cells, contributing to neurogenesis in specific regions like the hippocampus and ventricular-subventricular zone." DOI:10.1016/S0166-2236(02)02156-2|DOI:10.1111/joa.12006|DOI:10.1016/S0896-6273(00)80621-2|DOI:10.1016/j.pneurobio.2006.11.002 +679 CL:0000239 CL_0000239 "Brush border epithelial cells, also known as microvillar cells, are specialized cells predominantly found lining the small intestine and proximal tubules of the kidneys. They derive their name from their characteristic appearance under a light microscope, resembling a paintbrush's bristles due to a dense covering of microvilli on their apical surface. The microvilli are tiny, finger-like projections that greatly increase the surface area of these cells, optimizing nutrient absorption and enzymatic activity. + +The primary function of brush border epithelial cells in the small intestine is the absorption of digested nutrients. As food particles reach the small intestine, digestive enzymes present within the brush border, such as disaccharidases and peptidases, break down carbohydrates and proteins into simpler forms, such as glucose and amino acids. These simpler nutrients are readily absorbed through the microvilli into the bloodstream. Simultaneously, these cells contribute to maintaining the intestinal barrier, preventing the invasion of harmful substances or microorganisms into the systemic circulation. + +In the context of the kidneys, brush border epithelial cells are a crucial component of the proximal tubules. These cells aid in the reabsorption of ions, glucose, and amino acids from the filtrate, thereby playing an indispensable role in the regulation of the body's water and electrolyte balance. In addition to absorption, these cells also participate in the secretion of substances like creatinine and certain drugs into the kidney filtrate for subsequent excretion. " DOI:10.1083/jcb.201407015|DOI:10.1002/jcp.26033|DOI:10.1152/ajpgi.00005.2011|DOI:10.1073/pnas.0405179101 +680 CL:0000710 CL_0000710 "Neurecto-epithelial cells, also known as neuroepithelial cells, are a pivotal subset of cells that are mainly found during the early neural developmental phase within an organism. These cells serve crucial roles in the formation of the neural system during the creation of the body's network for signal transmission. They possess the ability to rapidly proliferate and differentiate into diverse types of neural cells, paving the way towards their prominent role in executing the complex development of the central nervous system (CNS). + +The primary function of neurecto-epithelial cells is to form the neural tube. The neural tube is a tubular structure that eventually develops into major components of the CNS, including the spinal cord and brain. The neurecto-epithelial cells line the inside of this tube, and, upon receiving specific signals, they divide and differentiate to create more specialized cell types.. Neurecto-epithelial cells, therefore, serve as the primary source of neural diversity, contributing to the construction of the highly complex neural network of the body. + +Additionally, neurecto-epithelial cells also play an essential role in neural migration. Following differentiation, the cells produced must find their correct location within the neural system, a process facilitated by neurecto-epithelial cells. They manifest microscopic protrusions called basal processes that assist newly differentiated cells in their journey to their final location. Thus, through their critical involvement in the formation, differentiation, and guidance of neural cells, neurecto-epithelial cells function as fundamental components within the neural developmental process." DOI:10.1038/ncomms14167|DOI:10.1016/j.abb.2012.07.016|DOI:10.1006/excr.1995.1173|DOI:10.1083/jcb.201901077|DOI:10.1002/wdev.28 +681 CL:0000749 CL_0000749 "ON-bipolar cells, classified as retinal bipolar cells, contribute to the visual processing pathway. Located in the inner nuclear layer of the retina, they serve as intermediary neurons, transmitting visual information from photoreceptors to ganglion cells. This facilitates the conversion of received light signals into electrical signals processed by the brain for visual image formation. A notable feature of ON-bipolar cells is their ability to respond positively to light increase, unlike OFF-bipolar cells that respond to a decrease in light. + +Specifically, ON-bipolar cells connect to photoreceptor cells (rod and cone cells) and receive their synapses. Their major function involves transducing graded potentials from photoreceptors, representing varying brightness levels in the visual field. During increased light or light onset, ON-bipolar cells depolarize, leading to heightened neurotransmitter release and signaling to downstream neurons. + +The unique arrangement of ON-bipolar cells in the retina segregates the visual field into lit and unlit regions, enhancing spatial contrast detection and aiding edge detection. The diversity of ON-bipolar cells, resulting from different connectivity to various photoreceptors, contributes to the high resolution and color perception of the visual system. Dysfunction in these cells is a pathological hallmark of retinal diseases, including night blindness and specific retinitis pigmentosa types. + + + + +" DOI:10.1146/annurev-vision-102016-061338|DOI:10.1016/j.preteyeres.2008.03.003|DOI:10.7554/eLife.20041|DOI:10.1016/j.ajhg.2009.10.003|DOI:10.1016/j.exer.2016.03.018 +682 CL:0000750 CL_0000750 "OFF-bipolar cells, a specific type of neuron in the retina, constitute one of the two primary bipolar cell types, the other being ON-bipolar cells. Playing a vital role in visual processing, they transmit signals from photoreceptors (rods and cones) to ganglion cells, which then relay information to the brain. Unlike ON-bipolar cells, OFF-bipolar cells are hyperpolarized by light and depolarized by darkness. + +OFF-bipolar cells exhibit structural diversity, characterized by differences in both dendritic arbor size and the specific photoreceptors to which they establish connections. Positioned in the inner nuclear layer of the retina, they have polarized extensions receiving inputs from photoreceptors and transmitting information to ganglion cells. Their function converts photoreceptor signals for processing by the visual system. + +Working in conjunction with ON-bipolar cells, OFF-bipolar cells contribute to creating and enhancing contrast in visual input. Their design employs feedforward inhibition, enhancing visual contrast and detail by emphasizing dark surrounded by light (or vice versa) areas. " https://www.ncbi.nlm.nih.gov/books/NBK11521/|DOI:10.2174/1570159X13999150122165018 +683 CL:0000255 CL_0000255 "Eukaryotic cells, distinguished by their intricate structure, constitute a foundational cell type found in a diverse range of organisms, including humans, animals, plants, and fungi. Their defining features include a membrane-bound nucleus housing genetic material and various organelles such as mitochondria, endoplasmic reticulum, and Golgi apparatus, each specialized for crucial cellular functions. + +The function of a eukaryotic cell depends on its organelles and its role within the larger organism. The nucleus governs cell activities through gene expression and plays a vital role in reproduction, while mitochondria generate energy by converting nutrients into ATP through respiration. The endoplasmic reticulum packages synthesized proteins for transport, and the Golgi apparatus processes and dispatches proteins to their destinations. Cytoplasm, the cell's internal environment, facilitates biochemical reactions. + +Despite specialization, eukaryotic cells share core functions like cellular growth, division, response to stimuli, and protein synthesis, processing, and transport. Interactions among eukaryotic cells contribute collectively to the overall function and survival of the organism." https://www.sciencedirect.com/topics/immunology-and-microbiology/eukaryotic-cell|https://www.ncbi.nlm.nih.gov/books/NBK26907/ +684 CL:0000244 CL_0000244 "Transitional epithelial cells, also known as urothelial cells, are a special type of epithelial cell that lines the urinary tract system's internal surfaces, specifically the renal pelvis, ureter, bladder, and portions of the urethra. The main characteristic feature of these cells is their ability to adapt to and withstand the distension that naturally occurs within the urinary tract system due to the storage and excretion of urine. These cells are so named because they are transitional in appearance and nature, meaning they can change from a relaxed, cuboidal form to a squished, squamous form in response to mechanical stress. + +The primary function of transitional epithelial cells is to form a robust, impermeable barrier between the urine and the body's internal environment. These cells prevent potential harmful materials and substances present in the urine, like bacterial toxins, from being reabsorbed into the bloodstream, especially when the bladder fills with urine. Additionally, the cells are biologically designed to minimize any damage to this protective lining by creating a highly effective barrier. This protective function is of extreme importance to the health and survival of an organism. Another important aspect of transitional epithelial cells is their ability to regenerate and repair the epithelial barrier's integrity after injury. This regenerative capacity is pivotal within the urinary tract system, especially given this system's continual exposure to potentially harmful agents. " DOI:10.1038/s41385-022-00565-0|DOI:10.1152/ajprenal.00327.2009|DOI:10.1152/physrev.00041.2019|DOI:10.1152/physrev.00030.2012|DOI:10.1002/dvdy.24487 +685 CL:0000764 CL_0000764 "Erythroid lineage cells, integral to the body's blood-forming system, originate from multipotent hematopoietic stem cells in the bone marrow. Through erythropoiesis, a developmental pathway involving various stages and cell types, these cells transform into mature red blood cells (erythrocytes). Their primary function lies in facilitating oxygen transport throughout the body, accomplished by the mature erythrocytes containing hemoglobin. + +Erythroid lineage cells regulate hemoglobin production during maturation, ejecting their nucleus and organelles to maximize space for hemoglobin, enhancing oxygen transport efficiency. The finely tuned process of erythropoiesis responds to the body's oxygen needs. When tissue oxygen levels are low, the kidneys release erythropoietin, a hormone stimulating the bone marrow to produce more erythroid progenitor cells and mature red cells. + +This regulation is crucial, as dysfunction may lead to disorders like anemia or polycythemia. Thus, erythroid lineage cells not only play a vital role in oxygen transport but also serve as a key model for understanding blood cell development, maturation, and related diseases." DOI:10.1101/cshperspect.a011601|DOI:10.1016/j.dci.2015.12.012|DOI:10.1016/j.bcmd.2009.02.001 +686 CL:0000765 CL_0000765 "Erythroblasts, also known as normoblasts, are immature red blood cells primarily found in the bone marrow. They serve as precursors to mature red blood cells (erythrocytes) and play a crucial role in erythropoiesis, the production of red blood cells. The main function of erythroblasts is to synthesize hemoglobin, a vital molecule enabling erythrocytes to carry oxygen throughout the body. Identifiable by their round shape and a nucleus rich in DNA, a feature absent in mature erythrocytes, erythroblasts undergo a series of developmental stages. + +Erythropoiesis initiates with multipotent hematopoietic stem cells differentiating into proerythroblasts under the influence of growth factors, notably erythropoietin. Proerythroblasts then transform into erythroblasts, characterized by multiple rounds of mitosis and hemoglobin accumulation. Throughout this process, erythroblasts lose cellular organelles and reduce in size, progressing through basophilic erythroblast, polychromatic erythroblast, and orthochromatic erythroblast stages. + +In the final phase, orthochromatic erythroblasts expel their nuclei, becoming reticulocytes—nearing full maturation. Reticulocytes shed their reticular substance to become fully mature erythrocytes. Precise regulation of erythropoiesis is crucial for maintaining red blood cell balance, as disruptions can lead to blood disorders like anemia or polycythemia. " https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/erythroblast|DOI:10.1007/s12551-019-00579-2|DOI:10.1073/pnas.0909296106|DOI:10.1182/blood.2021011044 +687 CL:0000786 CL_0000786 "Plasma cells, or effector B cells, play a crucial role in the immune system. These cells stand out for their ability to produce antibodies (immunoglobulins), essential proteins aiding the immune system in recognizing and neutralizing pathogens like bacteria and viruses. Serving as the ultimate stage in the B-cell lineage, plasma cells act as the body's primary defense mechanism against infections and diseases. + +Distinguished by their distinctive nucleus, intricate endoplasmic reticulum, and ample cytoplasm, plasma cells are uniquely adapted for their chief function of antibody production. Each plasma cell specializes in producing a single type of antibody, specifically tailored to combat a particular antigen. When exposed to an antigen during an immune response, B cells transform into plasmablasts, immature plasma cells that subsequently mature and proliferate into fully functional plasma cells capable of generating large quantities of the specific antibody required. + +While circulating in the blood and lymphatic system, plasma cells also reside in various tissues and organs, providing localized immune defense. Long-lived plasma cells, a subset, persist in the body for extended periods, maintaining long-term immune memory and ensuring a rapid response upon re-exposure to the same antigen. However, any disruption in plasma cell regulation can lead to disorders such as multiple myeloma and autoimmune diseases. Hence, the role of plasma cells is pivotal not only in combatting infections but also in maintaining the overall balance of the immune system." https://www.ncbi.nlm.nih.gov/books/NBK556082/|https://www.ncbi.nlm.nih.gov/books/NBK27092/|DOI:10.1111/imr.12732 +688 CL:0000823 CL_0000823 "Immature natural killer (NK) cells, as their name implies, are a developmental stage of NK cells, critical components of the innate immune system. NK cells are specialized large granular lymphocytes that play a critical role in early host defense mechanisms against infections and cancer. Immature NK cells are constantly produced in the bone marrow through hematopoiesis from lymphoid progenitor cells and undergo various stages of maturation and activation before they can fully exert their immune functions. + +The primary function of mature NK cells is to mediate cytotoxicity and produce immune-regulating cytokines, contributing to the immune response. Unlike their mature counterparts, immature NK cells show a reduced functional capability and require further maturation to fully engage in their immune functions. During their maturation process, they acquire a range of surface receptors that aid in the identification and elimination of abnormal cells. These include inhibitory and stimulatory receptors that recognise major histocompatibility complex (MHC) class I molecules, largely dictating their function. + +The maturation process of NK cells involves a complex regulatory network, including transcriptional regulation, signal transduction and programming of effector functions. A balance of signals from stimulatory and inhibitory receptors guides the responsiveness of an NK cell. In situations where inhibitory signals predominate (e.g when MHC Class I molecules are recognised), NK cells remain inactive. Conversely, lowered MHC Class I expression or signals from stimulatory ligands can activate these cells. Thus, immature NK cells are not just inactive forms of NK cells, but are dynamic entities in the process of maturation, contributing to the versatility and adaptability of the immune system. Even though immature NK cells might not be fully functionally equipped, they provide an essential reservoir for maintaining a comprehensive and functional NK cell pool in response to varying immune challenges." DOI:10.1038/nri2154|DOI:10.3389/fimmu.2018.01869|DOI:10.3389/fimmu.2022.1061959|DOI:10.1038/nri3044|DOI:10.1186/ar4232 +689 CL:0000824 CL_0000824 "Mature natural killer cells, often abbreviated as NK cells, represent a crucial component of our innate immune defense system, specifically geared towards tackling viral infections and tumor growth. These cells are a type of lymphocyte, essentially a white blood cell, and are a part of the body's first line of defense, reacting fairly quickly to a wide array of threats. Once mature, these cells are characterized by their large granular lymphocytes - a cellular component filled with enzymes that can destroy invading cells. + +The primary function of mature natural killer cells lies in their ability to recognize and eliminate virus-infected cells and malignant tumor cells. Unlike other immune cells, NK cells do not require the presence of antigens to identify harmful cells. Instead, they detect alterations on the surface of distressed cells, particularly those that are lacking normal protein markers. Upon identification, NK cells bind to these distressed cells using special receptors, leading to the activation of an immune response. + +Activation of mature natural killer cells triggers the release of cytotoxic granules, which further elicits a sequence of events culminating in the death of target cells. This is achieved via two main pathways: the granule exocytosis pathway and the death-receptor-induced apoptosis pathway, both leading to the death of target cells. Simultaneously, NK cells promote adaptive immune response by secreting a host of chemical signals called cytokines and chemokines, which serve to alert and activate other immune cells. Consequently, mature natural killer cells lie at the intersection of innate and adaptive immunity, making them an essential actor in maintaining overall immune homeostasis." "DOI:10.1038/s41577-022-00732-1|DOI:10.3389/fimmu.2018.01869|DOI:10.1084/jem.20181454 +|DOI:10.1111/j.1365-2567.2009.03123.x|DOI:10.1038/onc.2012.206" +690 CL:0000905 CL_0000905 "Effector memory CD4-positive, alpha-beta T cells, often simply referred to as effector memory T cells or Tem, play a critical role in the adaptive immune system. They belong to the subset of T lymphocytes, which are pivotal for monitoring and responding to foreign antigens in the human body. As a subset of memory T cells, these cells contribute to long-term immunological memory and are key players in the response to previously encountered pathogens. + +Effector memory CD4-positive, alpha-beta T cells are defined by cell surface expression of alpha-beta T cell receptors (TCRs) and CD4 molecules, which facilitates antigen recognition and subsequent immune response initiation. Additionally, these cells typically express CD45RO as a marker of memory T cells and lack expression of CCR7 and CD62L, distinguishing them from central memory T cells. + +Effector memory T cells are produced following a primary immune response, although the mechanisms by which some activated T cells may become memory T cells is still unclear. Effector memory T cells are usually found in the blood and traffic through peripheral organs. These cells migrate to inflamed tissue during an immune response. They are named for their ability to rapidly secrete effector cytokines upon antigen re-exposure to activate the secondary immune response, thus providing a long-lived pool of effector T cells. Effector memory T cells can be further subdivided into TH1, TH2 or TH17 memory cells, with each able to orchestrate a different immune response." DOI:10.1038/s41590-023-01510-4|DOI:10.1615/critrevimmunol.2014010373|DOI:10.1111/imm.12929|DOI:10.3390/cells9030531 +691 CL:0000904 CL_0000904 "Central memory CD4-positive, alpha-beta T cells, usually referred to as central memory T cells or Tcm, are a subset of T cells, one of the critical components of the adaptive immune system. Derived from activated effector T cells, these central memory T cells play a pivotal role in maintaining long-term immunity against previously encountered antigens. They contribute to long-term immunological memory that provides the immune system its ability to swiftly respond to known pathogens. + +Central memory CD4-positive, alpha-beta T cells are defined by the expression of alpha-beta T cell receptors (TCRs) and CD4 molecules, which facilitates antigen recognition and subsequent immune response initiation. Additionally, these cells typically express CD45RO as a marker of memory T cells and CCR7 and CD62L, distinguishing them from effector memory T cells which do not express the latter two markers. Their CD62L and CCR7 expressions promote their trafficking through lymphoid tissues, thereby positioning them at the forefront of antigen recognition and immune response activation. + +Central memory T cells traffic between secondary lymphoid organs, providing immune surveillance by sampling antigens that have collected in the lymphoid tissues. Upon antigen re-challenge, these cells can secrete interleukin-2 (IL-2), though typically not cytokine signatures that are produced by other effector T cell subsets. Central memory T cells are also capable of significant proliferation, providing a reservoir for effector memory T cells." DOI:10.1038/s41590-023-01510-4|DOI:10.1615/critrevimmunol.2014010373|DOI:10.1111/imm.12929|DOI:10.3390/cells9030531 +692 CL:0000910 CL_0000910 "Cytotoxic T cells, also known as CD8+ T cells, are a subtype of T cells and a critical component of the immune system. These cells play a vital role in host defense against viral infections and the development of tumor immunity. Cytotoxic T cells are identified by their cell surface glycoprotein CD8, which is crucial for their interaction with infected or transformed cells. + +Cytotoxic T cells are primarily responsible for the recognition and elimination of host cells that are either infected by viruses or have become tumorigenic. They are equipped with specialized receptors - T cell receptors (TCRs) on their cell surface. These receptors identify specific antigens presented on the surface of infected or transformed cells by a molecule known as the Major Histocompatibility Complex (MHC). Specifically, cytotoxic T cells interact with antigens presented by MHC Class I molecules, which are often found on the surface of virus-infected cells or cancer cells. + +Upon recognition of the specific antigen, the cytotoxic T cell becomes activated and subsequently eliminates the target cell. The killing mechanism involves the secretion of cytotoxic compounds such as perforin and granzymes. Perforin forms pores in the target cell membrane while granzymes enter through these pores and induce programmed cell death, or apoptosis." DOI:10.1038/s41416-020-01048-4|DOI:10.1016/j.immuni.2011.07.010|DOI:10.1038/s41577-021-00574-3|DOI:10.5114/ceji.2014.42135|DOI:10.1146/annurev.immunol.26.021607.090404 +693 CL:0000939 CL_0000939 "The CD16-positive, CD56-dim natural killer (NK) cells are critical components of the innate immune system, in the human body. This group of cells is characterized by a specific marker profile - expressing high levels of CD16 (FCγRIIIA) and lower or dim intensity of CD56 (NCAM). CD16 is an important activatory receptor that facilitates antibody-dependent cellular cytotoxicity through the recognition of antibody-coated cells, while CD56 is an important adhesion molecule that helps NK cells interact with their target cells. + +Functionally, these cells are regarded as the most mature NK cells and are the primary NK cell subset found in the circulatory blood. These cells are well-known for their high cytotoxic potential, along with their ability to rapidly produce a wide range of cytokines and chemokines in response to stimulation. Their potent cytotoxicity is largely mediated by the direct killing of virally infected cells and cancer cells, as well as the ability to produce inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). This makes them a key mediator for limiting the initial dissemination and growth of malignant or infected cells within the body. + +Furthermore, the CD16-positive, CD56-dim NK cells serve a significant role in immune regulation and modulation of adaptive immune responses. They are capable of interacting with other immune cells such as dendritic cells, macrophages, and T cells to modulate immune responses through both direct cellular contacts and the release of soluble factors. These multifaceted interactions allow CD16-positive, CD56-dim NK cells to effectuate both effector and regulatory functions, thereby maintaining a balance between immune defense and immune tolerance, and preventing autoimmunity." DOI:10.1111/j.1365-2567.2008.03027.x|DOI:10.4049/jimmunol.179.1.89|DOI:10.3389/fcimb.2020.00162|DOI:10.1073/pnas.1012356108 +694 CL:0001029 CL_0001029 "The common dendritic progenitor (CDP) is a stem cell responsible for generating dendritic cell lineages crucial for immune function. + +CDPs primarily differentiate into two main types of dendritic cells: conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs). This diversification enhances the functional variety of the immune response. cDCs excel at capturing, processing, and presenting antigens to both naive and memory T-cells, guiding the adaptive immune response. Conversely, pDCs are potent cytokine producers, particularly interferons, vital for antiviral responses. + +Beyond generating dendritic cell subtypes, CDPs play a crucial role in maintaining homeostatic control of immune responses. Striking a balance between their progenitor state and commitment to specific dendritic cell lineages is essential for adapting to the body's varying needs. This delicate equilibrium ensures swift and appropriate responses against pathogens without triggering autoimmunity. + + + +" DOI:10.1146/annurev-immunol-020711-074950|DOI:10.3389/fimmu.2019.01222|DOI:10.3390/ijms23094885 +695 CL:0001034 CL_0001034 "A ""cell in vitro"" refers to a cell grown or manipulated outside its natural biological setting, typically in an artificial environment like a petri dish or test tube. These cells, commonly derived from cell culture practices, include primary cells directly sourced from living organisms or modified cell lines with indefinite proliferation capabilities. + +The characteristics of the in vitro cell depend on its source, but, generally, it provides a valuable platform for researchers to study various cellular processes such as division, growth, morphogenesis, and differentiation. It also allows investigation into internal mechanisms like protein synthesis and gene expression, offering insights into cell-cell interactions, responses to environmental factors, and the effects of chemicals, drugs, or pathogens on cellular physiology. + +In pharmacological studies, cells in vitro play a crucial role, serving as tools for screening pharmaceutical compounds and as disease progression model systems. They are also pivotal in genetic engineering studies, providing a controlled environment to observe changes in a cell's genetic information. Certain mammalian cell lines in vitro, thanks to their perpetual growth, have significantly contributed to breakthroughs in vaccine development and understanding cancer biology. While in vitro cells cannot fully replicate the complexities of living systems, they play a vital role in advancing our understanding of fundamental biological processes. + + + +" DOI:10.1016/B978-0-12-803077-6.00009-6|https://www.ncbi.nlm.nih.gov/books/NBK26851/|https://www.ncbi.nlm.nih.gov/books/NBK26851/ +696 CL:0001051 CL_0001051 "The CD4-positive, CXCR3-negative, CCR6-negative, alpha-beta T cell is a special class of T lymphocytes, key players in the immune system's adaptive responses. This subset of T cells plays a crucial role in modulating immune responses, including immune defense against infections, controlling autoimmunity, and maintaining body homeostasis. + +CD4, also known as T-helper cells, assist other T cells or B cells to accomplish their effector functions. These cells recognize antigens displayed on MHC class II molecules typically present on antigen-presenting cells (APCs) such as macrophages, dendritic cells, and B cells. Following the interaction with an antigen, CD4-positive T cells proliferate and differentiate into functionally specific subsets, such as Th1, Th2, and Th17 cells, which are characterized by the type of cytokines they produce and their immunological roles. + +The absence of chemokine receptors CXCR3 and CCR6 differentiates this T cell subtype from others. Lack of expression of CXCR3 and CCR6 are hallmarks of Th2 cells, that differentiate from naïve CD4+ T cells following TCR ligation and specific cytokine signaling. Th2 cell development and stabilization requires the master regulatory transcription factor GATA-3. Furthermore, IL-4-mediated activation of STAT6 is thought to play an important role in Th2 cell differentiation. + +The primary function of these cells is to coordinate the immune response against extracellular pathogens, particularly parasitic helminths. They achieve this primarily through the secretion of their signature cytokines – the interleukins IL-4, IL-5, and IL-13. Despite their critical roles in host defense, an overactive Th2 response can also lead to pathological outcomes such as allergy and asthma." DOI:10.1038/s41598-018-37846-3|DOI:10.1385/IR:28:1:25|DOI:10.1186/rr40|DOI:10.1155/2012/925135 +697 CL:0001063 CL_0001063 "Neoplastic cells, commonly known as cancer cells, represent a distinct cell type characterized by uncontrolled growth, division, and mutation. Originating from normal cells, they undergo genetic alterations driven by factors such as environmental influences, viral infections, chemical exposure, and inherited genetic defects. + +Similar to ordinary cells, neoplastic cells initially maintain the functions of their cell of origin. However, as they mutate and lose regulatory control, they deviate from their original function, prioritizing uncontrolled growth and survival over normal cellular duties. This relentless multiplication disrupts the structure and function of the tissue or organ they inhabit, leading to the clinical manifestations of cancer. + +Despite their aberrant behavior, neoplastic cells retain some characteristics of normal cell function, such as the fundamental ability to grow and divide, as well as utilization of mechanisms like metabolism and cell signaling. However, these processes are severely distorted, allowing cancer cells to evade death signals and enhance their own survival. Notably, neoplastic cells can also achieve a form of 'immortality' by activating the enzyme telomerase, extending their lifespan and enabling continuous replication. + + + + +" https://www.sciencedirect.com/topics/engineering/neoplastic-cell|DOI:10.4161/cc.23720 +698 CL:0001060 CL_0001060 "Hematopoietic oligopotent progenitor cells, lineage-negative, are pivotal in the intricate hematopoietic system, deriving from hematopoietic stem cells (HSCs) in the bone marrow. Their primary function involves generating various mature blood cell types, showcasing restricted differentiation potential while having the ability to transform into closely related cell types. + +Characterized by their ""lineage-negative"" status, these cells do not express specific hematopoietic lineage markers, indicating their relative immaturity and potential for further lineage commitment. Their inherent plasticity enables them to respond to hematopoietic growth factors and cytokines, guiding differentiation into erythroid, myeloid, lymphoid, or megakaryocyte populations. The specific lineage path adopted depends on signals received from the microenvironment. + +Functionally, lineage-negative hematopoietic oligopotent progenitor cells are vital for maintaining blood system homeostasis, ensuring a consistent output of mature blood cells throughout an individual's life. They also play a crucial role in rapidly producing blood cells in response to infections, blood loss, or other forms of physiological stress. Recognizing their essential role and potential is fundamental to therapeutic approaches in regenerative medicine, particularly in conditions affecting blood cell production and function, such as leukemia and anemia. + + + +" https://pubmed.ncbi.nlm.nih.gov/19325941/ +699 CL:0001064 CL_0001064 "A malignant cell, commonly associated with cancer, is characterized by uncontrolled growth, evasion of normal cell death, tissue invasion, and the induction of angiogenesis. These cells exhibit fundamental genetic mutations and alterations in normal cellular mechanisms, driving their uncontrollable proliferation. + +Functionally, malignant cells disrupt the typical cell cycle, manipulating it for continuous division and survival. They evade apoptosis, or programmed cell death, often through overproduction of anti-apoptotic proteins or mutations in pro-apoptotic proteins. + +Malignant cells also distinguish themselves by their ability to invade tissues and metastasize to other body sites. Unlike normal cells, they can detach, penetrate barriers like the basement membrane, and establish secondary tumors, causing harm in multiple organ systems. Additionally, they induce angiogenesis, creating their own blood supply to sustain rapid proliferation. + +While retaining some functions of their cell of origin, malignant cells undergo pathological reprogramming, prioritizing survival and propagation, leading to substantial harm to the host organism." DOI:10.1016/j.semcancer.2015.03.008|DOI:10.1002/jcb.21707|DOI:10.1016/j.semcancer.2022.10.006|https://www.ncbi.nlm.nih.gov/books/NBK9963/ +700 CL:0001061 CL_0001061 "An ""abnormal cell"" arises when it undergoes excessive growth and division or fails to undergo programmed cell death when necessary. This type of cell is also refered to as a neoplastic cell and can be classified as either benign (non-cancerous) or malignant (cancerous). + +Benign neoplasms, though non-cancerous, can still cause health issues depending on their size and location. Unlike malignant neoplasms, they typically do not invade nearby tissues or spread to distant sites in the body. Instead, they tend to grow slowly and remain localized. However, large benign tumors can exert pressure on surrounding structures, leading to symptoms such as pain, discomfort, or functional impairment. + +Malignant neoplasms, or cancers, are characterized by their ability to invade adjacent tissues and metastasize to distant organs through the bloodstream or lymphatic system. These tumors can disrupt normal bodily functions and have the potential to be life-threatening if left untreated. Malignant cells often exhibit abnormal morphology, increased proliferation rates, and the ability to evade the body's immune surveillance mechanisms. + + + +" https://www.cancer.gov/publications/dictionaries/cancer-terms/def/neoplasm|https://www.ncbi.nlm.nih.gov/books/NBK9963/|https://www.ncbi.nlm.nih.gov/books/NBK164700/ +701 CL:0001068 CL_0001068 "ILC1s, or Group 1 innate lymphoid cells, are a subset of the innate lymphoid cell family mainly concentrated in mucosal barriers like the intestine and liver. Playing a crucial role in the immediate response against pathogenic microorganisms, cellular transformations, and inflammation, ILC1s have two primary functions: cytokine secretion and cytotoxicity. + +ILC1s generate IFN-γ and exhibit the T-box transcription factors Eomesodermin (Eomes) and/or T-bet. They stimulate and regulate the immune response, aiding in defense against viral and bacterial infections. Additionally, they exhibit cytotoxic capabilities through the expression of natural cytotoxicity receptors and the production of granzyme B, a serine protease stored within granules. This allows ILC1s to induce cell death in tumor or virus-infected cells. However, ILC1 activation must be carefully regulated, as overactivity can lead to inflammatory diseases like inflammatory bowel disease, psoriasis, and rheumatoid arthritis." DOI:10.3389/fimmu.2016.00426|DOI:10.1016/j.imlet.2016.07.005|DOI:10.1016/j.bj.2020.10.001 +702 CL:0001074 CL_0001074 "The CD34-positive, CD56-positive, CD117-positive common innate lymphoid precursor, often shortened to CD34+CD56+CD117+ CILP, is a progenitor cell type of the human immune system. The naming of this cell type is based on the unique presence of three cell surface proteins: CD34, CD56 and CD117, which are respectively associated with stemness, innate immunity and cellular differentiation within the hematopoietic lineage. + +The primary function of these cells is to serve as precursor cells that can further differentiate into various mature innate lymphoid cells (ILCs). ILCs, which are essential components of the innate immune system, are responsible for responding to pathogens, maintaining mucosal barrier integrity, and modulating adaptive immune responses. The ability to differentiate into any type of ILCs, including NK cells, ILC1, ILC2, and ILC3, highlights the multilineage potential and intrinsic plasticity of these precursors, which is crucial for maintaining the homeostasis of the immune system. In addition to contributing to innate immunity, CD34+CD56+CD117+ CILPs also have a significant role in adaptive immunity through their ability to stimulate T-cell differentiation and function. " DOI:10.1016/j.immuni.2018.08.010|DOI:10.1038/s41423-019-0211-7|DOI:10.1016/j.immuni.2014.09.005|DOI:10.1016/j.immuni.2018.05.013|DOI:10.1007/978-981-10-5987-2_11 +703 CL:0001077 CL_0001077 "ILC1, an abbreviation for Group 1 Innate Lymphoid Cells, are an integral part of the human immune system. They play a vital role in initiating and promoting early immune responses, particularly positioned at barrier surfaces of the human body such as the skin and gut. ILC1s, like all ILCs, are lymphocyte-like and their primary function is to protect the host against challenging infections and diseases, predominantly of viral pathogens. + +While their integral part in the immune response is essential, abnormal ILC1 responses could potentially lead to pathological conditions. For example, dysregulated ILC1 activity has been implicated in chronic inflammation and autoimmune diseases such as inflammatory bowel disease and psoriasis. + +However, delineating ILC1 in humans is more complicated compared to their mouse counterparts. The presence of classical helper CD127+ ILC1, NK cells exhibiting diminished cytotoxicity, and a subset of cytotoxic ieILC1 pose challenges in establishing a consistent nomenclature for ILC1 and comparing them across various studies." DOI:10.1007/s00281-018-0688-7|DOI:10.1016/j.it.2020.08.009|DOI:10.1101/cshperspect.a030304 +704 CL:0001200 CL_0001200 "Lymphocytes of B lineage, CD19-positive, also known as CD19+B cells, are a critical component of the adaptive immune system. CD19 is a surface marker protein, contributing to antigen receptor signaling assemblies for B cell activation and regulation. CD19+B cells play a fundamental role in humoral immunity which underscores their role in the production of antibodies against specific antigens. These cells are found predominantly in the lymphoid tissue, peripheral blood, and bone marrow. + +CD19+B cells act as antigen-presenting cells (APCs) capable of activating T cells via major histocompatibility complex (MHC) II-restricted antigen presentation. Opportunely, these antigen-antibody interactions lead to B cell activation, proliferation, and differentiation into plasma cells, which in turn produce protective antibodies. This individual ability to recognize and respond to specific antigens enables CD19+B cells to initiate a targeted immune response, a distinguishing characteristic compared to components of the innate immune system. + +Furthermore, CD19+B cells express a unique B cell receptor (BCR) specific to a particular antigen. The BCR is a membrane-bound form of antibody that, once triggered, mediates intracellular signals promoting a variety of responses, including proliferation, differentiation, and secretion of protective antibodies. Importantly, the CD19 molecule enhances the responsiveness of the BCR by lowering the threshold for antigen-dependent stimulation. Put simply, the CD19 molecule amplifies the signal provided by the BCR interaction with the antigen, thus promoting the B cell response. This feedback mechanism sustains antibody production to fight infections effectively while ensuring the tolerogenic behavior of B cells towards self-antigens. " DOI:10.1186/2162-3619-1-36|DOI:10.1016/j.humimm.2018.04.013|DOI:10.3109/08916934.2014.921810|DOI:10.4049/jimmunol.170.1.73|DOI:10.1093/intimm/dxh266 +705 CL:0001204 CL_0001204 "CD4-positive, alpha-beta memory T cell, CD45RO-positive is a specialized subtype of T cells that play a critical role in adaptive immunity, which is the immune system's targeted response to specific pathogens. These cells are distinguished by the cell surface expression of alpha-beta T cell receptors (TCRs), the TCR co-receptor CD4, and the CD45RO isoform of the CD45 common leukocyte antigen. This combination of markers reflects the mature, memory status of these T cells. + +CD4-positive, alpha-beta memory T cells, CD45RO-positive are key players in the body's long-term immunological memory. Unlike naive T cells, which respond to a novel antigen and require up to 1-2 weeks to mount a full immune response, memory T cells respond rapidly and robustly when they encounter an antigen they have previously encountered. This is a result of their prior activation during an initial immune response. Following the resolution of the initial infection or injury, a small number of activated T cells survive to become memory T cells, retaining the ability to recognize the specific antigen related to that infection. The expression of the CD45RO marker identifies these cells as memory T cells, a population often contrasted to naive CD45RA-expressing T cells. + +In terms of function, when these CD4-positive, alpha-beta memory T cells, CD45RO-positive are re-exposed to their specific antigen, they proliferate and differentiate rapidly into high potency effector cells. This expedited response accounts for the swiftness and intensity of secondary immune responses to pathogens that have already been encountered. These memory T cells also activate B cells, resulting in antibody production, resulting in further neutralization of pathogens during the secondary response. The essential roles of CD4-positive, alpha-beta memory T cells, CD45RO-positive make them pivotal entities in managing pathogenic re-infections and vaccine strategies." DOI:10.1038/s41590-023-01510-4|DOI:10.1615/critrevimmunol.2014010373|DOI:10.1111/imm.12929|DOI:10.3390/cells9030531|DOI:10.3389/fimmu.2018.02394 +706 CL:0002031 CL_0002031 "A hematopoietic lineage restricted progenitor cell is a specialized type of stem cell crucial for the continuous generation and maturation of diverse blood cells throughout an organism's life. As integral components of the hematopoietic system, these cells, predominantly located in the bone marrow but also present in peripheral and umbilical cord blood, are designated as 'lineage restricted' due to their predetermined differentiation into specific blood cell types. + +This specialization results in the formation of various blood cell types, including erythrocytes, granulocytes, macrophages, dendritic cells, and lymphocytes. Functionally, hematopoietic lineage restricted progenitor cells play a critical role in supporting the immune system and facilitating oxygen transportation by regulating leukocytes and erythrocytes production. These cells are also important in therapeutic approaches for hematopoietic disorders such as leukemia and anemia. Additionally, they hold promise in regenerative medicine for replenishing blood cells. " DOI:10.1515/BC.2008.092|DOI:10.3390/ijms24065862|DOI:10.15283/ijsc19127 +707 CL:0002032 CL_0002032 "Hematopoietic oligopotent progenitor cells are vital components within the hematopoietic system, overseeing the production and development of blood cells. As a subtype of hematopoietic progenitor cells, they are labeled 'oligopotent' due to their capability to differentiate into a limited set of blood cell types. Originating from multipotent hematopoietic stem cells with the ability to generate any blood cell, these progenitor cells gradually transition from multipotency to an oligopotent state, restricting their differentiation potential to a select few cell types. + +The primary role of hematopoietic oligopotent progenitor cells is to regulate the body's blood cell supply. Their specific functions vary based on the subtype of oligopotent progenitor cell. For instance, lymphoid progenitors can give rise to diverse lymphocytes like T cells, B cells, and natural killer cells, while myeloid progenitors differentiate into red blood cells, platelets, mast cells, and certain white blood cells such as granulocytes and monocytes. + +The differentiation process of these cells is finely tuned, responding to the body's physiological needs to produce the right types and quantities of cells based on external stimuli or conditions. Despite losing the ability to differentiate into any blood cell type, their capacity for self-renewal ensures a sustainable source of specific blood cells, contributing to a balanced hematopoietic system. " DOI:10.1002/wsbm.86|DOI:10.1186/s13287-019-1165-5 +708 CL:0002077 CL_0002077 "Ecto-epithelial cells, also known as ectodermal epithelial cells, make up the outer layer of the epithelial tissue and are derived from ectoderm, first of the three germ layers formed during the early stages of embryonic development. These cells play a critical role in the formation and function of various structures, including the skin (epidermis), hair, nails, mammary glands, and sweat glands. They also form part of the tissues lining the mouth, nasal passages, and even the cornea in the eye. + +In the skin, these cells have a protective role, forming a barrier against potential environmental hazards such as pathogens, UV radiation, and chemicals. Due to their role in skin formation, they are key contributors to the process of wound healing. They are also vital in the formation of keratin, a protein that lends strength and waterproofing capabilities to the skin, hair, and nails. These cells are further divided into various subtypes, each with its own specific properties and roles. For example, keratinocytes are ecto-epithelial cells responsible for producing keratin. Other subtypes include Langerhans cells and Merkel cells, respectively playing roles in immunity and touch sensation. " DOI:10.1038/s41380-022-01829-8|https://www.ncbi.nlm.nih.gov/books/NBK532977/|DOI:10.1016/S0012-1606(03)00325-7 +709 CL:0002078 CL_0002078 "Meso-epithelial cells are specialized cells that originate from mesenchymal tissue and adopt epithelial characteristics, playing crucial roles in various physiological functions. Typically, these cells are found lined along the internal and external surfaces of the body, contributing to the formation of various tissues and organs. Mesenchymal tissue, from which these cells derive, is primarily embryonic tissue that can differentiate into various cell types, including muscle, bone, and connective tissues. With the transformation into meso-epithelial cells, these can perform much more specialized functions relating to both epithelial and mesenchymal tissues. + +These cells are known for their key role in the process of epithelial-mesenchymal transition (EMT) and the reverse process, mesenchymal-epithelial transition (MET). During these processes, epithelial cells acquire mesenchymal cell traits and vice versa, which allow these cells to acquire enhanced mobility, invasiveness, and increased resistance to apoptosis. EMT and MET are critical in many developmental and pathological processes, including gastrulation, neural tube formation, heart development, as well as metastasis and tumorigenesis. These transitions are essential for wound healing, tissue regeneration, organ fibrosis, and metastsis in adult organisms." DOI:10.1038/s41556-018-0195-z|DOI:10.1038/nrc.2017.118|DOI:10.1002/dvg.23531 +710 CL:0002174 CL_0002174 "An ovarian follicle consists of a developing oocyte enveloped by one or more layers of cells referred to as follicular cells. Within this cell population, there are various subtypes including granulosa cells and cumulus cells.A primary follicle is characterized by a solitary layer of cuboidal granulosa cells, while a secondary follicle features multiple layers of granulosa cells. + +Granulosa cells are the main coordinators for ovarian follicular development. Their primary role is the production of sex hormones, particularly estrogen, achieved through the conversion of androgens with the enzymatic assistance of aromatase. Additionally, they support the growth of the oocyte within the primordial follicle, providing physical assistance during its maturation. Cumulus cells are a group of closely associated granulosa cells that surround and provide nourishment to oocytes. + +These cells also initiate signals essential for ovulation. Through a process known as ""gap junction intercellular communication,"" follicular cells interact with the oocyte, facilitating the exchange of small molecules. This involves the exchange of small molecules that allow the cells to respond concurrently to signals inducing growth, development, and finally, ovulation. Post-ovulation, these cells undergo luteinization to form the corpus luteum, producing progesterone crucial for early pregnancy maintenance. In summary, follicular cells in the ovary are essential for successful human reproduction, overseeing follicular development, coordinating ovulation onset, and contributing to crucial post-ovulatory events." DOI:10.1590/1806-9282.20230175|DOI:10.1002/rmb2.12010|https://training.seer.cancer.gov/anatomy/reproductive/female/ovaries.html|DOI:10.7717/peerj.1761|https://www.sciencedirect.com/topics/neuroscience/ovarian-follicle +711 CL:0002159 CL_0002159 "The general ecto-epithelial cells are a crucial component of the body's foremost barrier. They belong to the epithelial tissue category, one of the primary tissue types in multicellular organisms. These cells form the body's outermost layer, providing the first line of defense against various external threats including pathogens, toxins, and physical injury. They also play a key role in defining the boundary between the body's internal and external environments, serving as a semi-permeable border that regulates substance exchange between these binary environments. Structurally, these cells are characterized by their tightly-packed arrangement that forms a continuous sheet. + +Their core functionalities include protection, absorption, secretion, and sensation. They provide protection against mechanical and chemical damage, and pathogen entry into underlying body tissues. They also absorb nutrients and other essential substances from the surrounding environment, either through simple or facilitated diffusion or active transport. In terms of secretion, these cells produce a variety of functional substances, including enzymes, hormones, and mucus, facilitating regulatory as well as protective mechanisms. Some ecto-epithelial cells, particularly those on the skin and mucous membranes, are additionally evolved for sensation, as they contain nerve endings that respond to touch, pressure, temperature, or pain." https://www.ncbi.nlm.nih.gov/books/NBK532977/|DOI:10.1016/S0012-1606(03)00325-7|DOI:10.1016/j.cub.2021.07.078 +712 CL:0002194 CL_0002194 "A monopoietic cell is a precursor cell involved in the formation of monocytes (monopoiesis). The process of human monopoiesis is tightly regulated, beginning in the hematopoietic stem cell (HSC) compartment of the bone marrow and culminating in the generation of mature monocytes circulating in the blood. + +This cell type includes monoblasts and promonocyte. Monoblasts are characterized as large cells measuring 20-30 μm, with a round or oval nucleus, fine chromatin, a distinct nucleolus, and basophilic cytoplasm containing few azurophilic granules. On the other hand, promonocytes have an indented or lobulated nucleus shape and their nucleoli are less distrinct than monoblasts. + +Both monoblasts and promonocytes play a vital role in the body's immune response by differentiating into monocytes and subsequently macrophages or dendritic cells. These cells are critical for phagocytosis, antigen presentation, and the initiation of immune responses. They also participate in tissue repair and the regulation of immune responses, ensuring the body's health and defense against pathogens. +" https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/monoblast|DOI:10.4081/hr.2018.7823|DOI:10.3390/jcm10112264|https://www.ncbi.nlm.nih.gov/books/NBK557618/|DOI:10.1038/s41418-019-0297-6 +713 CL:0002202 CL_0002202 "The epithelial cells of the tracheobronchial tree play a crucial role in the functionality and maintenance of the respiratory system. Primarily, they constitute a physical barrier which protects the respiratory tract from external environmental factors such as pollutants, allergens, pathogens, and noxious substances. This layer of cells lines the airways of the tracheobronchial tree, from the trachea to the terminal bronchioles, and is integral to the maintenance of tissue homeostasis and respiratory health. + +The specialized, ciliated pseudostratified columnar epithelium of the tracheobronchial tree has several key functions. Their characteristic ciliations propel mucus, trapped particulates, and pathogens upward and out of the respiratory system, while the goblet cells interspersed among them secrete mucus, thus playing a role in the mucociliary clearance mechanism. Furthermore, these cells operate as a critical component of the immune system. Their pattern recognition receptors, such as Toll-like receptors, recognize various pathogens and trigger an immune response to protect the lungs from infection. + +Additionally, these cells are involved in the synthesis and metabolism of several bioactive mediators, including leukotrienes and prostaglandins, hence contributing to the regulation of the inflammatory processes in the respiratory tract. Moreover, they act as effector cells in the allergic responses and are known to produce various chemokines and cytokines, thus playing a pivotal role in the host defense mechanism." DOI:10.1152/japplphysiol.00984.2010|DOI:10.1111/ahe.12272|DOI:10.1038/s41577-020-00477-9 +714 CL:0002222 CL_0002222 "Vertebrate lens cells, also known as crystalline lens cells or simply lens cells, are crucial for focusing light onto the retina and ensuring clear vision. Originating from ectodermal tissue, these cells start as simple cuboidal epithelial cells, evolving over time into unique and intricate structures. + +There are two main types of lens cells: anterior lens epithelial cells (LECs) and lens fiber cells. Anterior LECs, forming a monolayer on the inner surface of the anterior lens capsule, manage growth, repair, and lens homeostasis. They can self-renew and differentiate into fiber cells, ensuring continuous lens growth throughout a vertebrate's life. + +Lens fiber cells, constituting the majority of the lens, contribute to its light-focusing ability. These transparent, elongated cells organize into tightly packed layers, enhancing the lens's refractive properties. During maturation, they lose intracellular organelles to minimize light scattering and increase transparency, crucial for proper eye function. Additionally, these cells produce crystallin proteins, influencing the lens's refractive index and contributing to protection and homeostasis. The organized cooperation of vertebrate lens cells is vital for the structure, function, and maintenance of the crystalline lens, ensuring clear vision." DOI:10.1242/dev.107953|DOI:10.1038/s41598-020-73625-9|DOI:10.1016/j.semcdb.2006.10.011 +715 CL:0000737 CL_0000737 "Striated muscle cells are highly specialized cells primarily responsible for voluntary movement in animals. Morphologically, these muscle cells have a striped or band-like appearance when examined under a microscope, which is a direct result of their unique internal structure featuring overlapping proteins. This distinct cell type is part of the muscular system and plays a pivotal role in biological functions that require muscle contraction such as locomotion, posture control, and the maintenance of bodily functions such as heartbeats and digestion. + +Despite being uniform in structure, striated muscle cells are further classified into two types: skeletal and cardiac muscle cells. Skeletal muscle cells are attached to the skeletal system and their contraction manifests as bodily movement. They are multinucleated, meaning they possess multiple nuclei, and they exhibit a cylindrical shape that can span lengths of a whole muscle. Cardiac muscle cells, on the other hand, are smaller, branched, and mainly constitute the myocardium, or the muscular wall of the heart. These cells only have one or two nuclei and their rhythmic, involuntary contractions maintain the beating of the heart. + +The function of striated muscle cells revolves around their ability to contract and generate force. This is achieved through a complex sequence of events known as the sliding filament model. In this process, the sarcomere involves overlapping actin and myosin proteins, which interact and slide past each other, leading to the shortening and lengthening of the muscle fiber. This process is influenced by neural stimuli and hormonal control, with energy provided by the cellular process of respiration. Thus, striated muscle cells function as the principal mediators of voluntary movement and cardiac function." DOI:10.1007/s00018-016-2285-z|DOI:10.1152/physrev.00040.2020|DOI:10.1152/ajpcell.00050.2017|DOI:10.1002/(SICI)1521-1878(200002)22:2<188::AID-BIES10>3.0.CO;2-T +716 CL:0002320 CL_0002320 "Connective tissue cells constitute a diverse group of cells that are central to the structure and function of the body's tissues and organs. As the crucial structural component of connective tissue, the most abundant tissue type in the body, these cells are responsible for producing and maintaining the extracellular matrix. This matrix, comprising ground substance and fibers, forms a supportive framework facilitating nutrient and waste exchange and contributing to the strength and flexibility of connective tissues. + +The primary types of connective tissue cells include fibroblasts, adipocytes (fat cells), and immune cells like macrophages, mast cells, and leukocytes. Fibroblasts, the most abundant, synthesize both fibers and ground substance. Adipocytes store energy, provide insulation, and protect organs, while immune cells defend against pathogens and aid in inflammation. + +These cells also play critical roles in wound healing, tissue repair, and regeneration, influencing diseases such as fibrosis, autoimmune conditions, and cancers. Hyperactive fibroblasts contribute to excessive extracellular matrix production in fibrosis, disrupting normal tissue architecture. In autoimmune diseases and cancers, immune cell behavior in connective tissue is altered. + + + + + +" https://training.seer.cancer.gov/anatomy/cells_tissues_membranes/tissues/connective.html|https://www.ncbi.nlm.nih.gov/books/NBK538534/|https://www.ncbi.nlm.nih.gov/books/NBK541065/|DOI:10.3389/fbioe.2022.958381 +717 CL:0002308 CL_0002308 "Epithelial cells of skin glands are specialized cells that play a key role in the structure and function of skin glands. These glands are categorized into two main types: sebaceous glands and sweat glands. Both types of glands are crucial for maintaining homeostasis and protecting the body from external stressors. Epithelial cells in the skin glands exhibit a polarized structure and organization, allowing them to carry out their primary functions effectively. + +Epithelial cells of the sebaceous glands are primarily responsible for producing and releasing sebum, a complex mixture of lipids and proteins. Sebum plays a crucial role in forming a protective barrier on the surface of the skin, thereby preventing the penetration of harmful microorganisms and ensuring skin hydration. These cells undergo a process known as holocrine secretion, in which the entire cell disintegrates to deliver its content, resulting in the continuous turnover of sebaceous gland cells. + +As for the sweat glands, they contain secretory epithelial cells. These cells are responsible for the production and secretion of sweat, a liquid consisting of water, salts, and small amounts of urea. Sweat has a critical role in thermoregulation as its evaporation from the skin surface results in cooling the body. Sweat also helps in the excretion of waste products and maintaining the pH of the skin. Additionally, in some mammals, these cells can produce scent for communication and social interaction purposes. Epithelial cells in the sweat glands undergo merocrine secretion where they release their product upon stimulation, such as during times of stress or high body temperature, without the cell itself being destroyed or damaged. + +" https://www.ncbi.nlm.nih.gov/books/NBK499819/|DOI:10.1080/23328940.2019.1632145|https://www.ncbi.nlm.nih.gov/books/NBK542322/|https://www.ncbi.nlm.nih.gov/books/NBK482278/ +718 CL:0002343 CL_0002343 "The decidual natural killer cell, often referred to as dNK cell, is a specific type of natural killer cell that is typically found in the uterus, particularly during the early stages of pregnancy. These cells, predominant immune cells in the decidual layer of the uterus, are unique to humans and have distinct functional characteristics and phenotypic markers that differentiate them from other types of natural killer cells. Unlike other NK cells that typically have cytotoxic functions, decidual NK cells have certain specialized roles that are particularly important during pregnancy. + +One of the primary roles of these cells is their contribution to the successful formation of a placenta. They facilitate the process of placentation by aiding in the remodeling of spiral arteries, which is crucial for establishing adequate blood flow to the developing fetus. dNK cells secrete a series of different growth factors, cytokines, and angiogenic factors which aid in the modification of the uterine environment to accommodate the implantation and nutrition of the embryo, promoting fetal growth and development. + +Additionally, decidual NK cells exhibit immunomodulatory properties. They play a significant function in regulating the maternal immune response to the implanted embryo, thereby preventing an undesirable immune response against the semi-allogeneic fetus. dNK cells have immune tolerance properties, which help to establish and maintain a delicate balance between defending against potential pathogens and permitting the growth of the fetus. Despite their limited cytotoxic activity, decidual NK cells can still respond to pathological stimuli, making them an integral part of the immune defense mechanism during pregnancy. Evidently, the unique functional characteristics of decidual natural killer cells underscore their importance in reproductive biology and maternal-fetal immune tolerance." DOI:10.1016/j.ebiom.2018.12.053|DOI:10.3389/fimmu.2021.728291|DOI:10.1111/imm.12218|DOI:10.3389/fimmu.2019.01397 +719 CL:0002355 CL_0002355 "The primitive red blood cell, also known as proerythroblast, represents an early stage in erythropoiesis—the formation of red blood cells essential for oxygen transport in the body. Originating in the initial embryonic phase, these cells emerge in the primitive yolk sac, a key site for primitive hematopoiesis occurring exclusively during embryonic development. + +Characterized by their larger size and the presence of a nucleus, primitive red blood cells undergo replication while in circulation. They carry a significantly high hemoglobin content, essential for efficient oxygen transport, particularly in low-oxygen environments during embryonic growth. + +Another distinctive feature is their progressive differentiation into mature erythrocytes, a vital aspect of definitive erythropoiesis. This process involves the removal of the nucleus, leading to the formation of smaller, biconcave, non-nucleated mature erythrocytes crucial in adult organisms. However, during embryonic development, primitive red blood cells play a pivotal role in ensuring adequate oxygen supply to growing tissues until the bone marrow matures to produce definitive erythrocytes." https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/proerythroblast|DOI:10.1182/blood-2012-01-153486|DOI:10.3389/fphys.2014.00003|DOI:10.1186/s12951-023-02060-5 +720 CL:0002417 CL_0002417 "A primitive erythroid lineage cell is a fundamental component of hematopoiesis, the intricate process of blood cell formation in the body. This embryonic cell specifically belongs to the erythroid lineage and plays a critical role during mammalian embryogenesis. Descending directly from mesodermal cells, it is among the earliest blood cells to emerge in the embryo, crucial for feto-maternal exchanges in early mammalian development. + +The primary function of a primitive erythroid lineage cell is to differentiate into primitive erythrocytes or larger red blood cells with nuclei. These erythrocytes have a short lifespan and support the rapidly growing embryo until definitive hematopoiesis is established. Despite their transient nature, primitive erythroid lineage cells impact the formation and function of definitive red blood cells, influencing the hematopoietic system established later in development." DOI:10.3389/fphys.2014.00003|DOI:10.1101/cshperspect.a011601 +721 CL:0002422 CL_0002422 "While some species, such as birds, fishes, amphibians, and reptiles, have nucleated red blood cells (RBCs), most mammals have enucleuated RBCs. The enucleated reticulocyte marks an intermediate phase in the life cycle of RBCs, emerging after the expulsion of the nucleus from a reticulocyte. This enucleation process contributes to the distinctive biconcave shape of RBCs, optimizing them for efficient gas transportation and filtration through narrow capillaries. + +These cells retains cytoplasmic RNA briefly after enucleation, allowing for limited protein synthesis. This step signifies the concluding phase of erythropoiesis, a vital process enabling the reticulocyte to mature into an erythrocyte, priming it for its primary function. + +The main role of enucleated reticulocytes is their transformation into fully mature RBCs, the primary carriers of oxygen in the body. They transport oxygen from the lungs to cells and facilitate the removal of carbon dioxide from cells to the lungs. + +" https://www.sciencedirect.com/topics/medicine-and-dentistry/reticulocyte|https://www.ncbi.nlm.nih.gov/books/NBK264/|DOI:10.3389/fphys.2018.00829|DOI:10.4049/jimmunol.1800565 +722 CL:0002522 CL_0002522 "The kidney's role in filtering blood and concentrating metabolic waste into urine occurs within a complex and functionally sophisticated unit known as the renal glomerulus. The renal filtration cells that support this process are referred to as podocytes and nephrocytes. + +Podocytes are found in the kidneys of vertebrates, particularly in the outermost layer of the glomerulus, where they form part of the filtration barrier. Their intricate foot processes interdigitate to create filtration slits, allowing for the selective passage of substances into the renal tubules while preventing the loss of important molecules like proteins. + +On the other hand, nephrocytes are present in certain invertebrates, such as insects, functioning similarly to podocytes by filtering waste materials and excess fluids from the hemolymph. While podocytes are exclusive to vertebrates, nephrocytes play a crucial role in maintaining fluid balance and waste management in invertebrates, contributing to overall physiological homeostasis. +" DOI:10.1083/jcb.201410017|DOI:10.1155/2018/5697436|DOI:10.3389/fmed.2022.801837|DOI:10.1038/nature07526 +723 CL:0002625 CL_0002625 "Seminiferous tubule epithelial cells, also known as Sertoli cells, are found in the testis of males and are integral to the process of spermatogenesis, the production of mature sperm cells. Positioned within the seminiferous tubules alongside developing sperm cells, they constitute an essential part of the blood-testis barrier, which prevents the entry of systemic substances and immune cells into the lumen, thereby protecting the male germ line from systemic infections. This specialized region, which partitions the seminiferous epithelium into basal and adluminal compartments, also provides the controlled microenvironment essential for the maturation of germ cells and the differentiation processes that occur during spermatogenesis. + +These cells display a unique ability to nurse developing sperm cells while regulating the stages of their differentiation. Seminiferous tubule epithelial cells provide essential nutrients and growth factors to nurture the developing spermatocytes and spermatids while also aiding in the removal and detoxification of their waste products. They are also pivotal in the structural organization of the seminiferous tubules and play a key role in the shaping of early spermatids into mature spermatozoa, even participating in the final release of mature sperm into the lumen, a process known as spermiation. + +In addition to playing an integral role in spermatogenesis, Sertoli cells can also be seen as immunomodulatory, given that they create a tolerogenic environment enabling the survival of genetically modified offspring cells, as they express unique sets of auto-antigens during the different stages of differentiation. This immune privilege is critical for preventing auto-immunization against the maturing haploid germ cells, which could otherwise induce detrimental auto-immune reactions. Consequently, any disruption in the functioning of the seminiferous tubule epithelial cells can have adverse effects on fertility and overall male reproductive health." DOI:10.1016/j.semcdb.2021.06.016|https://www.ncbi.nlm.nih.gov/books/NBK560631/|DOI:10.1152/physiol.00001.2014|DOI:10.1093/biolre/ioy027|DOI:10.3389/fimmu.2022.913502 +724 CL:0002658 CL_0002658 "Glandular cells of the large intestine represent one of the main cell types found within the epithelial lining of the large intestine, particularly in the colon's glandular structures known as colonic crypts. They are a critical component of the epithelial barrier, which serves as the first line of defense against harmful microbes and toxins in the intestine while facilitating essential nutrient absorption. Consisting primarily of enterocytes, large intestine goblet cells, and enteroendocrine cells of colon, each type of these cells performs distinct, vital roles in maintaining intestinal health. + +Enterocytes, the most abundant subtype of glandular cells in the large intestine, are responsible for the absorption of water, electrolytes and various nutrients from digested food. These cells have a highly developed brush border (microvilli) that increases their surface area, enhancing nutrient and water absorption. Meanwhile, large intestine goblet cells interspersed among enterocytes produce a protective layer of mucus that lubricates the intestine and traps potentially harmful microorganisms and toxins, preventing their contact with the epithelial cells and underlying tissues. + +Enteroendocrine cells of colon, though less in number, are exceedingly important for intestinal function and overall homeostasis. This glandular cell type secretes various hormones that regulate fluid balance, glucose metabolism, digestion, and appetite, among other processes. Dysregulation or damage to these glandular cells can disrupt normal gut function, paving the way for a variety of disorders, including inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, and neoplasms like colonic polyps and colorectal cancer. Therefore, the glandular cells of the large intestine are pivotal in the function and maintenance of the health of the digestive system." DOI:10.1038/nrc2392|DOI:10.1038/s41580-020-0278-0|DOI:10.1111/imr.12182|DOI:10.1007/s00441-016-2530-7 +725 CL:0008000 CL_0008000 "Non-striated muscle cells, also known as smooth muscle cells, are a type of muscle cell present across various tissues and systems in the body. Unlike striated muscle cells, non-striated muscle cells lack sarcomeres and their visible banding patterns due to the different orientation and packaging of myofilaments. They have a smooth uniform appearance, and are typically elongated and spindle-shaped, with a single, centrally located nucleus. The bodies of non-striated muscle cells are surrounded by a thin layer of endomysium, and they link together forming sheets of muscle tissues. + +The primary function of non-striated muscle cells is involuntary muscle control, allowing a variety of internal physiological processes to occur without conscious effort. Non-striated muscle cells are found in the walls of many organ systems including the intestinal tract, urinary bladder, blood vessels, uterus, and other parts of the body. They are responsible for several essential functions such as maintaining vascular resistance and regulating blood flow and pressure in the cardiovascular system, facilitating the movement of substances through the digestive tract, and contracting during childbirth. + +Non-striated muscle cells are distinct not only in their function but also in their regulation. They are controlled by the autonomic nervous system, hormones, or sometimes can function independently. Moreover, the non-striated muscle cells possess the ability to maintain contractile tension for long periods without using much energy or undergoing fatigue. This unique feature is vital for long-term functions such as maintaining the tone in the vascular system and continually pushing contents through the digestive tract. +" https://www.ncbi.nlm.nih.gov/books/NBK526125|DOI:10.1098/rstb.2017.0318|DOI:10.1038/nrgastro.2012.168|DOI:10.1152/physiolgenomics.00111.2010 +726 CL:0005018 CL_0005018 "Ghrelin secreting cells are specialized cells predominantly found within the stomach, principally in the gastric oxyntic glands of the stomach's fundus, and in smaller numbers in the duodenum and pancreas. These cells produce and secrete ghrelin, a key peptide hormone that plays a crucial role in a wide array of physiological processes. + +Ghrelin, often referred to as the 'hunger hormone', is the sole known peripherally-produced and centrally-acting peptide that stimulates food intake and promotes storage of consumed nutrients. Ghrelin also plays pivotal roles in maintaining the body's energy balance, influencing glucose metabolism, gastric motility, and acid secretion, promoting cell proliferation, and regulating immune responses. Moreover, this hormone also plays a role in the central nervous system, through its influence on stress response, mood, and cognition. + +The activity of ghrelin secreting-cells is regulated by nutrient availability. When the stomach is empty, these cells are triggered to secrete ghrelin, which in turn signals the brain to initiate feelings of hunger. Conversely, following a meal, the presence of nutrients in the gastrointestinal lumen inhibits ghrelin secretion, thus diminishing the sensations of hunger. Several other factors, including neuronal and hormonal inputs, also modulate the function of ghrelin secreting cells. Dysfunction or dysregulation in these cells or ghrelin signaling can contribute to several pathophysiological conditions, such as obesity, eating disorders, cachexia, and growth hormone deficiency." DOI:10.1016/j.molmet.2015.03.005|DOI:10.1038/s41574-023-00927-z|DOI:10.1038/srep15725|DOI:10.1111/apha.13588 +727 CL:0008007 CL_0008007 "Visceral muscle cells are an integral part of the contractile system within the walls of various organs and structures in the body, such as the gastrointestinal tract, the uterus, blood vessels, airways, and the urinary bladder. These cells include smooth muscle cells, which lack the striations characteristic of striated muscle cells like cardiac muscle cells and skeletal muscle fibers. + +Functionally, visceral muscle cells are responsible for involuntary movements that maintain the function of the organs they are located in. Unlike skeletal muscle cells, which are under voluntary control, the contractions of visceral muscle cells are not under conscious control. For instance, they enable the peristaltic movements that allow food to move through the digestive system, the dilation and constriction of blood vessels and airways, and the expulsion of urine from the bladder. These functions are crucial for homeostasis and the general health of an organism. + +In terms of structure, visceral muscle cells are elongated, spindle-shaped, and each contains a single nucleus. These cells are tightly bound together, creating sheets of muscles that function in unison. Their contraction is typically slow but sustained, due to a unique arrangement of actin and myosin filaments, which allows for prolonged contractile force. The inherent nature of these cells to contract and relax without tiring over extended periods of time hence enables them to effectively carry out their function of continuously regulating organ capacity and maintaining normal functioning of the body's internal environment." DOI:10.1038/s41569-019-0227-9|DOI:]10.1152/physrev.1998.78.3.811|DOI:10.1152/advan.00025.2003|DOI:10.1016/j.autneu.2009.10.006|DOI:10.1152/ajpcell.00253.2008 +728 CL:0008028 CL_0008028 "Visual system neurons are a crucial cell type that directly contributes to the major processes of vision. Within the intricate network of the nervous system, these cells play a significant role in transmitting the visual stimuli received by the eye to the respective processing centers in the brain. + +In the context of their functionality, visual system neurons communicate with various specialized cells in the eye that collect light stimulus, such as photoreceptor cells (rods and cones). Specific visual system neurons like retinal bipolar neurons take the signals from photoreceptors and convey them through the retinal ganglion cells that make up the optic nerve. This transmitted information reaches the brain and is later formulated into images in our consciousness, enabling us to perceive visual input from our environment. + +Visual system neurons are instrumental in forming the various aspects of visual perception - color, depth, motion, and shape. They not only help in the transmission of signals but also participate in processing visual stimuli at different levels of the visual system. Furthermore, the intricate connection and diverse types of visual system neurons influences visual reflexes and synchronized eye movements. A defect or malfunction in these neurons can lead to impaired vision or blindness, signifying their essential role in the visual system. " DOI:10.1038/nrn3783|DOI:10.1016/j.ydbio.2021.09.005|DOI:10.1146/annurev-vision-082114-035334|DOI:10.1126/science.201028|DOI:10.1016/j.preteyeres.2008.03.003 +729 CL:0008046 CL_0008046 "Extrafusal muscle fibers are the primary components of skeletal muscle fiber, which makes up a large part of the muscular system in vertebrates, including humans. These fibers are ubiquitous throughout the body and are responsible for generating force and facilitating a myriad of movements. Extrafusal muscle fibers differs from the intrafusal muscle fibers that serve as muscle spindles, a sensory receptor. Extrafusal muscle fibers facilitate body movement while intrafusal fibers provide the nervous system with information about muscle length and changes in muscle length. + +Extrafusal muscle fibers can be subdivided into two types based on their characteristics and function: slow-twitch and fast-twitch fibers. Slow-twitch fibers, also known as Type I fibers or slow muscle cells, are smaller, have a slower contractile speed and produce less force, but are more resistant to fatigue and are therefore preferred for sustained and steady activities such as maintaining posture or endurance running. Fast-twitch fibers, also known as Type II fibers or fast muscle cells, are larger in size, capable of producing more force, and have a faster contractile speed, making them optimal for short, rapid, and powerful bursts of movements like sprinting or jumping. However, they fatigue more quickly. + +The functionality of extrafusal muscle fibers is systematically coordinated with the central nervous system through motor neurons. Alpha motor neurons, a type of motor neuron, innervate extrafusal muscle fibers and initiate the contraction of the muscle, the mechanism which provides the force to move the skeleton. This process follows the all-or-nothing principle, whereby an action potential causes every fiber in a muscle unit to contract. Thus, extrafusal muscle fibers play a key role in the voluntary and involuntary motor activities that are integral to daily life. +" DOI:10.1002/(SICI)1097-4598(199604)19:4<488::AID-MUS9>3.0.CO;2-8|DOI:10.1152/jn.00071.2018|DOI:10.1085/jgp.201210773|DOI:10.1073/pnas.0906809106|DOI:10.1113/JP270561 +730 CL:0009010 CL_0009010 "Transit Amplifying Cells (TACs) are a unique type of progenitor cells crucial for human and animal tissue regeneration and cell turnover. They are vital for maintaining homeostasis and promoting growth in various tissues like skin, hematopoietic system, intestinal epithelium, and neural tissue. + +Acting as intermediaries, TACs combine the proliferation potential of stem cells with the specialization of differentiated cells. For instance, in the skin, TACs migrate through layers, rapidly dividing and differentiating into various cell types, ensuring quick cell turnover for tissue regeneration after injury or normal processes. + +Dysregulation of TACs may contribute to conditions like cancer, where their rapid proliferation potential may lead to continuous cell division and tumor formation. Ongoing research in cell biology and oncology aims to understand the molecular mechanics governing TACs, with the goal of utilizing their regenerative potential in medicine and developing innovative anticancer strategies." DOI:10.1016/j.cell.2014.02.057|DOI:10.3389/fbioe.2023.1189225|DOI:10.1002/wdev.282 +731 CL:0010021 CL_0010021 "Cardiac myoblasts are a distinctive precursor cell type that play a pivotal role in the development of the heart muscle, known as the myocardium. These precursor cells can undergo differentiation into mature heart muscle cells or cardiomyocytes. Cardiac myoblasts also have the ability to proliferate, which contributes to the formation and growth of the heart during development. + +Cardiac myoblasts are mainly involved in the regeneration and repair of cardiac tissues. After a myocardial injury, such as a heart attack, cardiac myoblasts may proliferate and differentiate to aid in tissue repair. However, this regenerative capacity in humans is limited. These cells express genes critical for heart development, such as GATA4, Nkx2.5, and Tbx5. Interactions between cardiac myoblasts and their environment also play a crucial role in heart development. Cardiac myoblasts respond to various signaling molecules, hormones, and mechanical forces, which guide their proliferation and differentiation into mature cardiomyocytes. +" DOI:10.1016/0014-4827(59)90127-2|DOI:10.1038/s41598-017-12869-4|DOI:10.1038/nm1618|DOI:10.1371/journal.pone.0129303 +732 CL:1000275 CL_1000275 "Smooth muscle cells of the small intestine form a key component of the enteric system which is imperative for gastrointestinal motility. These cells are a specialized subgroup of smooth muscle cells, specifically found in the layers of the small intestine. The small intestine represents a significant part of the digestive system and plays a crucial role in the absorption of nutrients into the bloodstream. + +Smooth muscle cells of the small intestine are predominantly responsible for creating the contractions and relaxations that constitute intestinal motility. They trigger these movements in a coordinated and rhythmic manner known as peristalsis and segmentation. Peristalsis is a form of longitudinal and sequential contraction that pushes food from the upper gastrointestinal tract to the lower parts. Segmentation works by squeezing the intestine randomly, thereby facilitating the mixing of food particles and increasing contact with absorptive surfaces. These two processes are critical for intestinal motility and an effective digestive process. + +Apart from facilitating transit of food through contractions, these smooth muscle cells play a role in controlling the diameter of the vessels and the blood flow in the small intestine by their constrictive ability. These smooth muscle cells also contribute to the structural integrity of the small intestine by forming a part of its muscularis externa and muscularis mucosae. Additionally, they interact with other cell types such as enteric neurons and interstitial cells of Cajal (ICC), forming an integrated cellular network that ensures optimal functioning of the intestinal tract." DOI:10.1038/nrgastro.2012.168|DOI:10.1007/978-981-13-5895-1_1|DOI:10.1053/j.gastro.2016.02.030|DOI:10.1038/s41575-020-0271-2|DOI:10.1111/j.1582-4934.2008.00352.x +733 CL:1000317 CL_1000317 "Intestinal villus goblet cells are a specialized type of epithelial cell that reside in the intestinal tract. They are most prominently found in the small intestine but can also be seen in the colon. Their name is derived from their unique shape which resembles a goblet when viewed under a microscope. But beyond their unique shape, these cells have important roles in maintaining the physiology and health of the intestinal lining. + +The primary role of intestinal villus goblet cells is the production and secretion of mucus, a critical component for the preservation and maintenance of the intestinal lining. From an anatomical perspective, the mucus layer aids in the locomotion of matter along the intestinal tract, creating a buffer from the mechanical stress created by the movement of food particles. At a microscopic level, the mucus forms a protective barrier against microorganisms and potentially harmful substances in the intestinal lumen, averting direct contact with the epithelial cells, and hence preserving the integrity of the intestinal mucosal barrier. + +Intestinal villus goblet cells also play a key role in immune response within the intestines. The mucus secreted by these cells contains various antimicrobial peptides and immunoglobin A, important components of the body's first line of defense of the immune system. With such, goblet cells provide a robust and specialized response to infectious microbes and contribute to overall gut homeostasis. In pathological conditions, such as inflammatory bowel diseases, the number and efficiency of intestinal villus goblet cells can be affected, leading to reduced mucus production and disruption of the protective barrier, further underscoring their crucial role in intestinal health. +" DOI:10.1038/s41575-022-00675-x|DOI:10.1038/s41385-018-0039-y|DOI:10.1038/nri.2016.88|DOI:10.1016/j.diff.2008.09.008 +734 CL:1000339 CL_1000339 "The Enterocyte of Epithelium Proper of Small Intestine represents a specific type of specialized epithelial cell typically found lining the internal surface of the small intestine, notably the ilium and jejunum. These cells are characterized by their columnar structure and dominate the intestinal epithelium, playing a crucial role in the digestion and absorption of nutrients derived from the food we consume. + +Functionally, enterocytes facilitate the final steps in the digestion process by absorbing simple carbohydrates, peptides, amino acids, fats, and vitamins, thus contributing significantly to nutrient acquisition. Enterocytes achieve this by enzymatic digestion on their luminal surface and then transport the resulting simple molecules into the bloodstream. Their apical surface, which faces the lumen of the intestine, is densely covered with microvilli, collectively termed the brush border, which significantly increase the cell's surface area, allowing for more efficient nutrient absorption. + +Enterocytes are also involved in immunity; they create a barrier to prevent unwanted materials and microorganisms from entering the body from the gut. Despite their absorptive function, enterocytes selectively absorb materials, allowing only nutrients and water while excluding harmful substances. Their junctions with adjacent cells are reinforced by tight junction proteins, ensuring a controlled uptake of substances and maintaining the integrity of the intestinal barrier. Indicative of their importance, these cells have a relatively fast turnover rate, being replaced every 4 to 5 days to continually maintain a functional and healthy digestive system." DOI:10.1016/j.micinf.2005.04.003|DOI:10.1111/j.1365-2249.2011.04523.x|DOI:10.1111/j.1365-2249.2011.04523.x|DOI:10.1371/journal.pbio.3001586|DOI:10.1038/nri3608 +735 CL:1000412 CL_1000412 "Endothelial cells of arterioles are specialized cells lining the interior surfaces of the arterioles - minute arteries that lead to capillaries. Arterioles, being the primary site of vascular resistance, play a vital role in controlling blood pressure and blood flow distribution, and the endothelial cells lining these arterioles have unique adaptations allowing them to fulfill this role effectively. The smaller diameter of arterioles, compared to larger arteries, naturally increases resistance to blood flow, which can be dynamically adjusted by the contraction or relaxation of vascular smooth muscle cells that these endothelial cells interact with. + +These cells play a major role in regulation of vasomotor tone, blood fluidity and clotting, permeability, white blood cell adhesion, and angiogenesis, contributing significantly to cardiovascular homeostasis. By releasing vasodilators, such as nitric oxide and prostacyclin, and vasoconstrictors, such as endothelin-1, they actively control the diameter of arterioles to help regulate blood flow and pressure. Additionally, they form a selectively permeable barrier between the lumen and surrounding tissue, controlling the passage of materials and the transit of white blood cells into and out of the bloodstream. + +In response to tissue damage or during the formation of new blood vessels (angiogenesis), endothelial cells can proliferate and migrate. They express various adhesion molecules enabling the adhesion and rolling of white blood cells, which is a prerequisite for these cells to leave the bloodstream in areas of inflammation. Further, these cells play a crucial role in hemostasis and thrombosis, as they synthesize and express anticoagulant molecules to prevent spontaneous clot formation under normal conditions. " DOI:10.1038/s41569-022-00770-1|DOI:10.1016/j.neuron.2017.10.012|DOI:10.1111/micc.12040|https://www.ncbi.nlm.nih.gov/books/NBK53240/|DOI:10.1186/s12872-015-0124-z +736 CL:1000504 CL_1000504 "The renal medulla, situated within the inner part of the kidney, is composed of medullary collecting ducts, loops of Henle, vasa recta, and the interstitium. The distinct spatial organization of these elements is vital for controlling urine concentration and facilitating other specialized functions of the kidney. + +The medullary collecting ducts extend from the cortex (outer part of the kidney) through the medulla and play a crucial role in the final adjustment of urine concentration. As urine travels through these ducts, water is reabsorbed, and the concentration of solutes increases. The reabsorption of water is influenced by hormones such as antidiuretic hormone (ADH), which is produced by the pituitary gland. + +The loops of Henle play a crucial role in the concentration of urine and the reabsorption of water and solutes. The unique anatomy of the loop, especially the descending and ascending limbs, creates a countercurrent multiplier system. This system establishes a concentration gradient in the medulla, enabling the kidney to produce concentrated urine and conserve water effectively. + + +" https://training.seer.cancer.gov/anatomy/urinary/components/kidney.html|DOI:10.4161/org.19308|DOI:10.1016/j.semnephrol.2009.03.008|https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/loop-of-henle +737 CL:1000616 CL_1000616 "The outer medulla is a region within the kidney and includes part of the loop of Henle and the distal convoluted tubule. It is predominantly organized into a region of parallel bundles of tubules and vessels, known as renal pyramids. + +This cell type can be further classified. Examples include the kidney loop of Henle medullary thick ascending and descending limb epithelial cells, as well as the kidney proximal straight tubule epithelial cell and outer renal medulla vasa recta cell. + +Cells in the outer medulla are crucial to the kidney's primary functions: filtering blood, eliminating waste, conserving electrolytes, and regulating acid-base balance. Involved in reabsorption and secretion processes within tubules and vessels, they actively contribute to urine concentration through the transport of solutes and water. + +Additionally, cells in the outer medulla act as an intricate sensor system, responding to changes in volume and osmotic concentration within the kidney. They play a key role in regulating blood pressure and filtration rate, responding to hormonal signals and releasing molecules like renin for blood pressure control. Ensuring the proper function of these cells is essential for maintaining the body's homeostasis, including fluid and electrolyte balance, blood pressure, and overall kidney function." DOI:10.4161/org.19308 +738 CL:1000612 CL_1000612 "The kidney corpuscle cell, also known as a renal corpuscle cell, is a crucial component of the renal corpuscle, a structure within the kidney responsible for initiating the blood filtration process to produce urine. Comprising the glomerulus and Bowman's capsule, the renal corpuscle relies on these cells to play a central role in the kidney's filtration system. + +During blood filtration, kidney corpuscle cells create an interface between blood and filtrate, allowing the removal of waste while retaining essential components in the bloodstream. The cells perform this through a combination of physical and specialized properties that are critical to an accurate filtering process. Some of these cells, such as endothelial cells in the glomerulus, are characterized by their fenestrations that help facilitate the filtration of plasma from the blood. These cells are specialized to permit the passage of fluid, while blocking the passage of blood cells and large proteins. Another type of corpuscle cell, the podocyte in Bowman's capsule, contributes with tentacle-like protrusions and slit diaphragms for further plasma filtration. + +Moreover, kidney corpuscle cells are implicated in disease states. Damage or pathology affecting these cells can reduce the kidney's filtering capacity, leading to kidney disease. For example, podocyte damage may cause protein leakage into urine (proteinuria), an early sign of kidney issues. Beyond routine filtration, renal corpuscle cells are vital for overall kidney health, serving as a crucial indicator for potential kidney-related problems." https://www.ncbi.nlm.nih.gov/books/NBK554544/|https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/renal-corpuscle|DOI:10.2215/CJN.09400913|https://www.ncbi.nlm.nih.gov/books/NBK554474|DOI:10.1016/j.kint.2016.01.012 +739 CL:1000618 CL_1000618 "The juxtaglomerular complex, also known as the juxtaglomerular apparatus, is pivotal in regulating kidney function, specifically blood filtration and pressure control. Within the nephron, the kidney's functional unit, this complex comprises three key cell types: juxtaglomerular cells (JG cells), macula densa cells, and extraglomerular mesangial cells. Each cell type has a vital role in governing kidney function. + +JG cells, or granular cells, are specialized smooth muscle cells in the afferent arterioles. They release renin, a hormone catalyzing the renin-angiotensin system, in response to low blood pressure. Macula densa cells, located in the distal convoluted tubule, sense changes in sodium chloride concentration and regulate renin release by JG cells accordingly. Extraglomerular mesangial cells, positioned between afferent and efferent arterioles, play a less understood role. They are believed to transmit signals between macula densa and JG cells, contributing to information exchange within the juxtaglomerular complex and helping regulate nephron filtration rates." https://www.sciencedirect.com/topics/medicine-and-dentistry/juxtaglomerular-apparatus|https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/juxtaglomerular-cell|DOI:10.1681/ASN.2009070759|https://www.sciencedirect.com/topics/neuroscience/extraglomerular-mesangial-cell|DOI:10.1111/j.1440-1681.1997.tb01240.x +740 CL:1000893 CL_1000893 "Kidney venous blood vessel cells, also known as renal venous endothelial cells, are integral to the kidney's vascular system. They play a critical role in constructing and maintaining the renal venous system, impacting the body's blood pressure, filtration, and waste elimination. Positioned in the lining of venous blood vessels in the kidneys, they share characteristics with other vascular endothelial cells. + +Their primary function is to facilitate the transport of deoxygenated blood from the kidneys back to the heart. After the kidneys filter toxins and eliminate waste as urine, these cells are crucial in returning purified, deoxygenated blood for reoxygenation. They also contribute to controlling fluid and solute exchange between blood and kidney tissues, with the permeability of the vascular endothelium, regulated by these cells, playing a key role. + +Beyond being a biological conduit, renal venous endothelial cells interact with surrounding cells, tissues, and serum components, serving a vital role in cellular crosstalk and immune response. Recent studies highlight their active involvement in kidney-related diseases like renal fibrosis and inflammation, making them important therapeutic targets. + + + + +" DOI:10.1038/s41581-021-00411-9|DOI:10.1159/000447607 +741 CL:1001036 CL_1001036 "The vasa recta refers to a network of blood vessels associated with the kidneys. The endothelial cells in the vasa recta are instrumental in maintaining the delicate balance of salt and water in the bloodstream, warranting the normal functioning of the kidneys. They are primarily located in the renal medulla, which contains the loops of Henle and the collecting ducts. + +The primary function of the vasa recta is to participate in the countercurrent exchange system, a crucial mechanism for establishing and maintaining the concentration gradient in the kidney's medulla. This gradient is essential for the process of urine concentration. The vasa recta runs parallel to the nephron's loop of Henle, and as blood flows through these vessels, it undergoes exchange with the surrounding interstitial fluid. This exchange allows for the reabsorption of water and solutes, helping to preserve the hypertonic environment of the medulla and facilitating the production of concentrated urine." https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/vasa-recta|DOI:10.1016/j.semnephrol.2009.03.008 +742 CL:1001138 CL_1001138 "Cells located in the interlobular artery play a crucial role in the kidney's arterial and microcirculatory system. These arteries are integral to the renal vasculature, with their walls containing smooth muscle cells. These cells have the responsibility of regulating blood flow to the nephrons, which serve as the functional units of the kidney. Additionally, they participate in autoregulation, ensuring a consistent renal blood flow despite variations in systemic blood pressure. The health or functionality of these cells is paramount, as issues could potentially result in kidney dysfunction, emphasizing their vital contribution to overall health and homeostasis. + + + + + +" https://www.sciencedirect.com/topics/medicine-and-dentistry/interlobular-arteries +743 CL:1001216 CL_1001216 Interlobular artery endothelial cells are a specific type of endothelial cell found within the interlobular arteries in the kidneys. The prime function of these cells is to regulate the passage of fluids and molecules across the arterial wall, thus directly impacting kidney function as a filtering organ. These cells also play a pivotal role in maintaining the homeostatic balance in the kidney, balancing the passage of electrolytes, hormones, and other important molecules under normal conditions and responding to the stress under abnormal or pathological conditions like kidney diseases. In addition, these cells have an influential role in angiogenesis, the process by which new blood vessels form from pre-existing ones. This is particularly significant during the repair and regeneration of kidney tissues following injury or disease-related damage. DOI:10.1016/B978-0-12-415759-0.00047-9|DOI:10.1038/sj.ki.5001725 +744 CL:1001320 CL_1001320 Urethra cells are a specialized type of cell that make up the urethra, a crucial part of the urinary tract in both male and female mammals. The main function of urethra cells is to enable efficient and controlled urine passage through peristalsis, preventing backflow or uncontrolled expulsion. Urethra cells also contribute to maintaining sterility in the urinary tract. Goblet cells, a subtype, produce mucus as a physical barrier against harmful bacteria. Additionally, some urethra cells have immune functions, detecting pathogens and prompting immune responses to prevent urinary tract infections. Thus, urethra cells play a dual role: ensuring effective waste elimination and bolstering the body's defense against urinary tract infections. https://www.ncbi.nlm.nih.gov/books/NBK542238/ +745 CL:1001433 CL_1001433 "Epithelial cells of the exocrine pancreas are specialized cells that comprise a vast majority of the pancreas, specifically about 80%. They play a vital role in the digestive system of the body because of their function to produce and secrete digestive enzymes. A subset of these cells, pancreatic acinar and pancreatic ductal cells are organized into functional units termed acini, which in turn form the exocrine pancreas. Here, the produced enzymes are sent down the pancreatic ducts, directly to the duodenum – the first part of the small intestine – aiding in digestion. + +The exocrine pancreatic epithelial cells are integral in maintaining the body’s metabolism; they function to produce and secrete a variety of pancreatic juices to aid in digestion. The three major enzymes that these cells produce include proteases for protein digestion, amylase for carbohydrate digestion, and lipases for fat digestion. Additionally, these cells secrete bicarbonate ions to neutralize the acidity of the stomach content entering the small intestine, shielding it from acidic damage and ensuring the proper functioning of the digestive enzymes. + +Dysfunction in the epithelial cells of the exocrine pancreas is linked to common diseases such as pancreatitis, and cancer. Importantly, the regenerative abilities of the pancreas is vital for the pathogenesis of these diseases. Thus, the epithelial cells of the exocrine pancreas are not only critical for routine digestive processes but also have a significant bearing on broader health implications. +" DOI:10.1146/annurev-physiol-021014-071727|DOI:10.1038/nrgastro.2013.36|DOI:10.1136/gut.2005.065946|DOI:10.1038/s41575-019-0158-2|DOI:10.1053/j.gastro.2013.01.068 +746 CL:1001588 CL_1001588 "Colon glandular cells are a specific type of epithelial cells that make up part of the lining of the colon. These cells are a specific subset of colon epithelial cells and are organized into structures called glands or crypts that are vertically oriented and are arrayed along the interior surface of the colon. The primary function of these cells is to facilitate absorption, secrete mucus and maintain the barrier within the colon. + +The function of absorption mainly involves the absorption of water from wastes moving through the digestive system, leading to the formation of solid stool. This role is vital in preventing dehydration and maintaining the balance of fluids in the body. Another significant function of the colon glandular cells lies in their ability to secrete mucus. The mucus forms a protective lining that prevents the direct contact of waste material with the cellular lining of the colon, protecting them from damage and reducing friction during waste movement. + +Additionally, colon glandular cells serve a crucial role in maintaining the colon's barrier. They protect the body from harmful substances and microorganisms present in the gut. Any disruption to these cells can lead to disorders such as inflammatory bowel disease, including ulcerative colitis and Crohn's disease." DOI:10.1016/j.media.2016.08.008|DOI:10.1038/nrc2392|DOI:10.1126/science.abb1590|DOI:10.1111/imr.12182|DOI:10.1111/jgh.15734 +747 CL:1001591 CL_1001591 DOI:10.1530/REP-12-0279|DOI:10.21451/1984-3143-AR2018-0036|DOI:10.1016/S0143-4004(99)80008-3 +748 CL:1001598 CL_1001598 "Small intestine glandular cells play a critical role in the human digestive system. They include various specialized cell types, each with their unique function and are primarily found in the lining of the small intestine, specifically in the crypts of Lieberkühn and the villi. + +Small intestine glandular cells possess distinct morphological features, such as a brush or microvillus border, which increases their absorptive surface area. Within these microvilli are enzymes that function in the digestion of proteins, carbohydrates, and lipids, breaking them down for easier absorption. The cells are interconnected by tight junctions which ensure that nutrients are selectively and efficiently absorbed while preventing the access of pathogens or harmful substances. + +In addition to their role in nutrient absorption, small intestine glandular cells also produce and secrete several important substances to facilitate digestion and maintain a healthy gut environment. These include digestive enzymes, mucins for mucous production, and antimicrobial peptides to defend against bacterial invasion. Through these various roles, small intestine glandular cells are essential for sustaining overall health and wellbeing. Their dysfunction has been implicated in a number of gastrointestinal diseases, further highlighting their foundational importance in digestive system biology. +" DOI:10.1016/j.ceb.2003.10.012|DOI:10.1146/annurev-physiol-030212-183744|DOI:10.1007/112_2015_24|DOI:10.1007/s00018-011-0822-3|DOI:10.1038/nrgastro.2013.35 +749 CL:1001596 CL_1001596 "Salivary gland glandular cells are specialized cells that make up the majority of the salivary glands. These glands can be found in and around the oral cavity, with the major ones being the parotid, submandibular, and sublingual glands. The glandular cells are responsible for the production and secretion of saliva, an essential fluid for oral health and digestion. + +Salivary gland glandular cells exhibit remarkable functionality with multiple roles in oral and digestive health maintenance. They generate and secrete saliva that contributes over 98% water to maintain mouth moisture, lubricate food to facilitate swallowing, and aid in tasting food. The saliva produced by these cells also contains electrolytes, mucus, antimicrobial agents, and enzymes such as amylase and lipase, which initiate the digestion of dietary starches and fats, respectively. These cells also play an integral part in maintaining oral health by aiding in the elimination of oral microbes and the neutralization of oral acids, thereby reducing the risk of tooth decay or cavities. + +In response to stimulation, these glandular cells release saliva through a network of ducts that open into the mouth. This secretion process can be increased during eating or chewing and decreased during sleep or dehydration. Its dysregulation can lead to conditions such as dry mouth or xerostomia. Thus, the normal function of salivary gland glandular cells is essential for the maintenance of oral health and the digestive process. +" "DOI:10.1152/physrev.00015.2021|DOI:10.1111/odi.12867|DOI:10.1007/978-3-030-35784-9_2|DOI:10.7554/eLife.66170 +|DOI:10.1177/00220345211004842" +750 CL:1001599 CL_1001599 "Pancreas exocrine glandular cells are a specialized type of cell which comprises roughly 80-90% of the pancreas tissue. These include pancreatic acinar cells, which have a distinct shape similar to a small flask or pouch. They are organized into small, grape-like clusters or acini, which are connected to a series of progressively larger ducts leading to the main pancreatic duct. In addition, pancreatic goblet cells are another type of pancreas exocrine glandular cell found in lower frequency in the pancreatic duct. + +The primary function of pancreas exocrine glandular cells is the synthesis, storage and secretion of pancreatic enzymes. These enzymes, including amylase, lipase, and proteases, are vital for the digestion of food in the small intestine, particularly the breakdown of carbohydrates, fats and proteins. The secretion of pancreatic digestive enzymes is typically in an inactive precursor form to prevent auto-digestion, and are then activated within the lumen of the small intestine. + +The pancreas exocrine glandular cells possess an abundance of organelles, including ribosomes, rough endoplasmic reticulum and Golgi apparatuses, reflecting their high level of protein synthesis. Additionally, these cells demonstrate the typical polarity of glandular epithelial cells, with the nucleus and most of the cytoplasmic organelles situated towards the base of the cell, away from the lumen. This anatomical arrangement enables efficient secretion of enzymes and protects cellular structures from the potential damage caused by prematurely activated enzymes. These cells work in a sophisticated manner to ensure optimal digestion of food, playing a pivotal role in the body's nutrition absorption process." DOI:10.1016/j.biocel.2004.07.010|DOI:10.1016/j.biocel.2005.12.001|DOI:10.1016/j.biocel.2010.07.006|DOI:10.1038/nrgastro.2013.36|DOI:10.3998/panc.2020.15 +751 CL:1001601 CL_1001601 "Adrenal gland glandular cells form the primary functioning cells of the adrenal gland, an endocrine structure that is located superior to the kidneys. These cells are responsible for producing a variety of hormones essential to maintaining daily physiological activities and managing stress reactions. The adrenal gland consists of an outer cortex and an inner medulla, and the adrenal gland glandular cells constitute the predominant cell type of the adrenal cortex. + +Adrenal gland glandular cells are found in the three layers of the adrenal cortex, each responsible for manufacturing different types of steroid hormones, also known as corticosteroids. The outermost layer, called the zona glomerulosa, mainly produces mineralocorticoids such as aldosterone, which plays a crucial role in regulating the balance of salt and water in the body and maintaining blood pressure. The middle layer, known as the zona fasciculata, primarily produces glucocorticoids, including cortisol. This hormone assists in nutrient metabolism, helps maintain cardiovascular function, and is pivotal in the body's response to stress. Lastly, the inner layer referred to as the zona reticularis, generates a small amount of sex hormones. + +The adrenal gland glandular cells have a rich blood supply which facilitates the prompt transportation of the synthesized hormones into the bloodstream, from where they are delivered to their target organs. In addition, the production of these hormones is regulated by complex negative feedback mechanisms involving the hypothalamus and pituitary gland in the brain. In response to signals from these brain regions, adrenal gland glandular cells can rapidly adjust the production of hormones to meet the body's requirements during both physiological processes and abnormal or stressful conditions. Any dysfunction of the adrenal gland glandular cells can lead to various disorders such as Cushing's syndrome (overproduction of cortisol) or Addison's disease (insufficient hormone production)." DOI:10.1038/s41574-021-00491-4|DOI:10.3389/fnins.2016.00238|DOI:10.1016/j.mce.2012.10.023|https://www.ncbi.nlm.nih.gov/books/NBK278929/|DOI:10.1159/000216184 +752 CL:2000008 CL_2000008 "Microvascular endothelial cells are specialized types of endothelial cells that line the interior of microvessels, the smallest of blood vessels including arterioles, capillaries, and venules. These cells, interconnected with tight junctions, are major components of the blood-brain barrier and the inner blood-retina barrier, demonstrating their crucial role in regulating the molecular transport within and across these barriers. They facilitate the exchange of nutrients and waste products between the blood and tissues, and help filter out harmful substances. Their thin, flattened structure enables efficient gas exchange and nutrient transport between the blood and tissues. They participate in the recruitment of inflammatory cells at the site of injury or infection, modulate blood vessel tone, and participate in angiogenesis, the process of new blood vessel formation. + +Microvascular endothelial cells are implicated in numerous pathological conditions. The dysfunction of these cells has been associated with several cardiovascular diseases including hypertension, atherosclerosis, and stroke. They are also involved in the progression of diabetes, through their role in diabetic retinopathy, and other inflammatory diseases. In cancer, these cells significantly contribute to the formation of tumor blood vessels, promoting tumor growth and metastasis." DOI:10.1159/000511552|DOI:10.3390/cancers13061477|DOI:10.1186/s12967-023-04286-1|DOI:10.1161/CIRCHEARTFAILURE.120.006979|DOI:10.3389/fcell.2019.00044 +753 CL:2000005 CL_2000005 "Brain macroglial cells includes astrocytes of the cerebellum and forebrain. Astrocytes or astroglia derive their name from the Greek root ""astro,"" meaning star, due to their resemblance to ""stars in the night sky"" when observed on Golgi-stained samples. + +Astrocytes in the cerebellum undergo a tightly regulated developmental process and can be categorized based on their morphological features and distribution into three primary types: Bergmann glia (BG) and granular layer astrocytes within the cerebellar cortex, and fibrous astrocytes located in the cerebellar white matter. These cells are integral to numerous stages of cerebellar development, including granule cell migration, axonal growth, neuronal differentiation, and synapse formation. + +Astrocytes in the forebrain can be further categorized into astrocytes of the cerebral cortex and pituicytes. These cells are involved in a wide array of functions, including synaptic plasticity, neuronal communication, as well as neurotransmitter and hormone regulation." DOI:10.3390/jcm9030757|DOI:10.12998/wjcc.v11.i15.3385 +754 CL:2000041 CL_2000041 "The dermis microvascular lymphatic vessel endothelial cell is a specialized form of endothelial cell that specifically lines the microvascular lymphatic vessels situated in the dermis layer of the skin. This unique form of endothelial cell is crucial in the functioning and structure of the lymphatic system within the skin microvasculature. Notably, these cells are more than passive structural elements - they also engage in a host of biological activities that underscore their importance in maintaining skin health and overall homeostasis. + +Functionally, dermis microvascular lymphatic vessel endothelial cells are involved in the transport of lymph, a fluid containing white blood cells, throughout the lymphatic system and back to the bloodstream. This function is paramount for immune response, as it promotes the circulation of immune cells, like lymphocytes, and assists in the removal of potential pathogens. Additionally, these specific endothelial cells regulate the movement of cells and molecules between the interstitial space and the lymph vessel lumen, enabling fluid homeostasis and protein balance. + +These cells also play a critical role in angiogenesis and lymphangiogenesis - the formation of new blood vessels and lymphatic vessels, respectively. By dictating the processes of cell proliferation, migration and vessel maturation, dermis microvascular lymphatic vessel endothelial cells respond to angiogenic and lymphangiogenic signaling molecules and contribute to vascular growth both in normal physiological contexts, such as wound healing, and in pathological conditions, such as tumor progression or inflammatory skin diseases. +" DOI:10.1046/j.1087-0024.2000.00001.x|DOI:10.1177/002215549804600205|DOI:10.1073/pnas.242401399|DOI:10.1111/j.0021-8782.2004.00293.x|DOI:10.1038/nrc3677 +755 CL:4023008 CL_4023008 "Intratelencephalic-projecting glutamatergic cortical neurons, also known as intratelencephalic (IT) neurons, are a specific type of excitatory neuron that is found with projections restricted within the telencephalon of the brain. They are characterized by their synthesis and release of the neurotransmitter glutamate, which is the primary excitatory neurotransmitter in the central nervous system. Glutamate plays an indispensable role in neural activation, contributing majorly to synaptic plasticity, which is crucial for learning and memory. + +Intratelencephalic-projecting glutamatergic cortical neurons function by forming synaptic connections predominantly within the telencephalon, giving them the ability to transmit signals and information across different regions of the cerebral cortex. These neurons are fundamentally involved in higher cognitive functions facilitated by the cortex, which include but are not limited to, memory processing, attention, and conscious thought. These neurons are bidirectional, meaning they can send axons in both directions (towards the cortex and towards the striatum) which allows for more complex and multilayered responses to stimuli. + +The pathological dysfunctions of these neurons could potentially lead to various neurodevelopmental and neuropsychiatric disorders. As these glutamatergic neurons significantly influence synaptic plasticity, their dysfunction can result in cognitive impairments and disorders like schizophrenia, autism, and depression. Thus, the ability to modulate and regulate neural signaling allows the intratelencephalic-projecting glutamatergic cortical neurons to maintain optimal cerebral function." DOI:10.1523/JNEUROSCI.0150-18.2018|DOI:10.1038/nrn3469|DOI:10.1038/s41586-021-03223-w|DOI:10.3389/fnmol.2022.903175|DOI:10.1038/s41583-020-0315-1 +756 CL:4023009 CL_4023009 "The extratelencephalic-projecting glutamatergic cortical neuron is a vital cell subtype found within the cerebral cortex. Belonging to the broader class of glutamatergic neurons, this neuron type is characterized by its output connections that stretch outside the telencephalon, a region encompassing the cerebrum in the brain. This classification is notable for the release of glutamate, an excitatory neurotransmitter, which plays a pivotal role in neural communication, memory formation, learning, and regulation of various neurodevelopmental and neuropathological processes. + +Functionally, the extratelencephalic-projecting glutamatergic cortical neurons are responsible for transmitting information from the cortex to targets located outside the telencephalon, such as the thalamus, brainstem, and spinal cord. Their ability to facilitate long-range communication allows for the integration of different functional domains across the central nervous system, thereby contributing to various sensory, motor, cognitive, and affective functions. By enabling the exchange of signals between different brain structures, these neurons play an important role in coordinating complex activities and behaviors. + +The neurotransmitter glutamate produced and released by these neurons heightens the excitability of the connected neurons, enabling messages to pass more readily through the network. Extratelencephalic-projecting glutamatergic cortical neurons are integrated into precise circuitry with specific synaptic targets. Essentially, they contribute to the orchestrated relay of information throughout the brain and the overall coordination of neural networks. Defects or dysfunctions within these cells have been implicated in a variety of neurodevelopmental disorders and pathological conditions, highlighting their critical role in maintaining healthy brain function." DOI:10.1523/JNEUROSCI.0150-18.2018|DOI:10.1093/cercor/bhx012|DOI:10.1038/s41467-020-14952-3|DOI:10.1038/s41467-022-28493-4 +757 CL:0002242 CL_0002242 "A nucleate cell is a cell that possesses a nucleus, the key distinguishing structure of a eukaryotic cell. The term ""nucleate"" describes the widespread variety of cell types containing a nucleus found in multicellular organisms like plants, animals, and fungi, along with some single-celled entities such as protists. In contrast to prokaryotic cells which lack a nucleus, nucleate cells encase their genetic material within a nuclear membrane, creating a central control hub that coordinates the cell's primary functions. + +The primary feature of a nucleate cell lies in its nucleus, which plays an integral role in managing and coordinating the cell's activities. This structure contains the cell's DNA, the genetic blueprint that instructs cellular processes and dictates the production of proteins, vital units that execute many cell functions. By storing this DNA within a nucleus, the cell can control when specific genes are expressed, thus regulating the timing and quantity of protein production. This centralization and regulation of genetic information is crucial for maintaining the cell's health and functionality in multicellular life forms. + +In addition to housing genetic material, the nucleus of a nucleate cell is also responsible for the replication and transcription of DNA during cell division, a vital process in growth, repair, and reproduction. The nucleolus, a smaller yet critical structure within the nucleus, manufactures ribosomal RNA (rRNA), a vital component of ribosomes, the protein-synthesis machines of the cell. Thus, beyond being just a container of genetic material, the nucleus is an active participant in the cell's fundamental operations, making the nucleate cell a crucial component of diverse life forms. + +" DOI:10.1126/science.1439805|DOI:10.1098/rspb.1999.0817|DOI:10.1242/jcs.00779|DOI:10.1002/wrna.39 +758 CL:0002274 CL_0002274 "Histamine secreting cells include mast cells that are part of the body’s immune system and non-immune cells like type ECL enteroendocrine cells found in the stomach. The mast cells are mostly situated in connective tissues, particularly those near external environments including the skin, lungs, and gastrointestinal tract. They are an imperative component of the immune response, playing integral roles in wound healing and defense against pathogens. They are also responsible for the inflammation and allergic responses that characterize many immune disorders. + +In response to foreign pathogens, histamine secreting cells mainly secrete histamines, which are organic nitrogenous compounds involved in local immune responses. They also help regulate physiological function in the gut and act as a neurotransmitter in the central and peripheral nervous systems. The secretion of histamine by these cells is central in mediating inflammation and immediate hypersensitivity responses. This is particularly significant in the context of allergies, where mast cell activation leads to the release of large quantities of histamines and other proinflammatory agents. + +These cells also produce, store and secrete other substances. Specifically, mast cells also contain a variety of granules rich in heparin, proteases, and other inflammatory mediators such as cytokines, leukotrienes, and prostaglandin D2. Upon activation, these substances can be released at the site of an immunological threat, intensifying the body's defensive reaction. Therefore, these cells provide a plethora of additional immune functions essential for the body's defense against external threats. In conclusion, histamine secreting cells are multifaceted cells that contribute not only to our body's defense mechanism, but also significantly to proper functioning of the gut. +" DOI:10.1152/ajpcell.1999.277.5.C845|DOI:10.1038/ni1158|DOI:10.1038/s41577-022-00731-2|DOI:10.1038/sj.bjp.0706440|DOI:10.3389/fimmu.2015.00620 +759 CL:0002305 CL_0002305 "Epithelial cells of the distal tubule, also known as distal tubular epithelial cells, are located in the last portion of the renal tubule, beyond the loop of Henle, in the kidneys. These specialized cells play a critical role in the regulation of various electrolytes and homeostasis in the body. Epithelial cells of distal tubules help maintain the body's balance of water, sodium, potassium, and hydrogen ions to ensure body fluids' right concentration. + +These cells exhibit exceptional functional plasticity. They are equipped with ion channels, transporters, and pumps that facilitate selective reabsorption and excretion of electrolytes. They are actively involved in the reabsorption of Sodium ions and the secretion of Potassium and Hydrogen ions, thus playing a significant role in maintaining the acid-base balance in the blood. Specifically, these cells express numerous sodium channels, including the epithelial sodium channel (ENaC), which helps moderate the reabsorption of sodium and water from the urine." DOI:10.1016/j.biocel.2007.04.025|DOI:10.1159/000096947|DOI:10.1007/s00424-022-02732-5|DOI:10.2215/CJN.05920613 +760 CL:4023111 CL_4023111 "The cerebral cortex pyramidal neuron is a critical cell type in the cerebral cortex, the outer layer of the brain. Named after its pyramid-like shape, this neuron type is the most abundant excitatory neuron in the mammalian brain, playing a central role in the complex network of neural circuits involved in cognition and sensory interpretation. They are quintessential components of the mammalian prefrontal cortex, an area associated with complex cognitive behaviors, decision making, and moderating social behavior. + +In general, pyramidal neurons are characterized by a large cell body, also referred to as the soma, from which a multitude of dendritic branches extend. They are particularly distinctive due to their long, singular apical dendrite that stretches out towards the outer layer of the cortex, allowing for communication with several bands of cortical input. Additionally, these cells are equipped with multiple basal dendrites and a long axon that projects to distant targets. It's through the coordination of these dendritic and axonal components that cerebral cortex pyramidal neurons are involved in processing and integrating information both within the cortex and between cortical and subcortical regions. + +Functionally, cerebral cortex pyramidal neurons serve as the primary output neurons of the cortex, transmitting cortical information to all areas of the brain and spinal cord. This is achieved as the apical dendrites receive synaptic inputs, carrying out intricate analysis and processing operations before the results are taken to the output targets via the axon. Overall, through their complex integration and transmission of information, cerebral cortex pyramidal neurons serve as the cornerstone in the information processing and executive functions of the brain. +" DOI:10.1016/0301-0082(92)90015-7|DOI:10.1038/nrn2286|DOI:10.1093/cercor/bhv188|DOI:10.1002/jnr.23978|DOI:10.1016/j.conb.2008.05.006 +761 CL:4023154 CL_4023154 "Myelinating glial cells are specialized neuroglia that form an insulating layer (myelin sheath) around neuronal axons. One of the main functions of myelinating glial cells is to enhance the speed of signal transmission across neuronal axons while simultaneously saving the neuron's energy. + +There are two main subclasses: oligodendrocytes in the central nervous system (CNS) and myelinating Schwann cells in the peripheral nervous system (PNS). While both types produce myelin, they differ in their myelination patterns and support functions. + +Oligodendrocytes, found in the CNS, myelinate multiple axons simultaneously and provide nutritional support to neurons, contributing to nerve cell health. In contrast, Schwann cells in the PNS focus on individual axons and play a crucial role in nerve cell repair and regeneration following injury. " DOI:10.1111/jnc.14592|DOI:10.1016/j.conb.2023.102782|DOI:10.3390/ijms241612912|DOI:10.3390/cells9092131 +762 CL:4030031 CL_4030031 "Interstitial cells are found in the spaces between cells within various tissues. Examples include kidney interstitial cells, Leydig cells, pulmonary interstitial fibroblasts, and valve interstitial cells. + +Kidney interstitial cells reside between renal tubules and blood vessels in the kidney, consisting of fibroblasts, immune cells, pericytes, and myofibroblasts. They help maintain kidney structure, regulate fluid and electrolyte balance, modulate inflammation, and aid in repair and regeneration. + +On the other hand, Leydig cells, located in the testicular interstitial tissue, are essential for testosterone production, regulating male reproductive functions and secondary sexual characteristics. + +Pulmonary interstitial fibroblasts, found in lung parenchyma, contribute to postnatal lung development by maintaining lung structure. + +Within the heart, valve interstitial cells play a role in valve maintenance and function. Research suggests that these cells are involved in the pathophysiology of heart valve calcification." DOI:10.2215/CJN.00640114|DOI:10.1002/mrd.22648|DOI:10.1016/j.heliyon.2023.e19428|DOI:10.1161/JAHA.117.006339 +763 CL:4030034 CL_4030034 "Respiratory ciliated cells, also known as ciliated columnar epithelial cells, are a distinct cell type primarily lining the respiratory tract. They have a columnar shape and hair-like cilia on their surface, and can be found in the trachea, bronchi, and bronchioles + +The main function of respiratory ciliated cells is to facilitate the movement of mucus along the respiratory tract. Goblet cells produce mucus containing trapped particles, and the coordinated motion of the cilia propels this mucus upward and away from the lungs. This process, known as mucociliary clearance, maintains respiratory hygiene and safeguards the lungs from infections. + +Beyond mucociliary clearance, respiratory ciliated cells also contribute to sensing and responding to the external environment. The cells possess receptors that detect chemical and mechanical stimuli, allowing the body to respond appropriately to inhaled substances or changes in breathing conditions. Recent research suggests their potential involvement in regulating the immune response during respiratory diseases, highlighting their role in immune modulation within the respiratory tract." DOI:10.1101/cshperspect.a028241|https://www.sciencedirect.com/topics/immunology-and-microbiology/respiratory-epithelium|https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/respiratory-tract|DOI:10.3390/biology10020095|DOI:10.1152/ajplung.00283.2020 +764 CL:4023047 CL_4023047 "The ""L2/3 intratelencephalic projecting glutamatergic neuron of the primary motor cortex"" is a specialized neuron type located in layer 2/3 of the brain's primary motor cortex (M1 region). + +These neurons project their axons within the telencephalon – the embryonic region that gives rise to the cerebral cortex and its associated structures. As a highly specialized cell type, the L2/3 intratelencephalic projecting glutamatergic neurons are distinguished through their primary neurotransmitter, glutamate, and their unique projection pattern within the intratelencephalic area of the brain, which includes cortical and subcortical regions. + +Like other glutamatergic neurons, L2/3 intratelencephalic glutamatergic neurons utilize glutamate, the main excitatory neurotransmitter, crucial for normal brain function. These neurons facilitate excitatory synaptic transmission, contributing to the initiation and control of voluntary movements in the primary motor cortex. Their excitatory nature promotes cell activation and communication, crucial for precise, coordinated movements. + + + + + + +" DOI:10.1016/j.neuron.2018.10.032 +765 CL:4023073 CL_4023073 "Choroid plexus cells, also called choroidal cells, are specialized epithelial cells located in the choroid plexus of the brain. Situated adjacent to the pia mater layer bordering cerebrospinal fluid-filled cavities, these cells play pivotal roles in maintaining brain health and are integral to the central nervous system. + +A primary function of choroid plexus cells is the production of cerebrospinal fluid (CSF), a clear fluid crucial for cushioning the brain and spinal cord, delivering nutrients, and removing waste products. Operating as a filtration system, these cells generate CSF from blood plasma, regulating the brain environment by selectively allowing certain molecules to pass and filtering out harmful substances. + +Furthermore, choroid plexus cells contribute significantly to the central nervous system's immune response. Releasing various immune molecules and interacting with immune cells, they provide an additional line of defense against potential pathogens or harmful substances. Their central location in the brain's ventricles positions them as key players in maintaining brain homeostasis. Research links abnormalities in choroid plexus cells to neurodegenerative diseases like Alzheimer’s and disorders such as schizophrenia, underscoring their crucial role in preserving brain health. " https://www.ncbi.nlm.nih.gov/books/NBK538156/|https://www.ncbi.nlm.nih.gov/books/NBK519007/|DOI:10.1152/physrev.00060.2021 +766 CL:0011026 CL_0011026 "Progenitor cells are a specialized type of biological cell that can differentiate into specific cell types. While akin to stem cells in their differentiation capacity, progenitor cells are more limited in divisions and are already somewhat specialized. They can divide a restricted number of times and differentiate into a few closely related cell types, unlike stem cells with broader differentiation potential. + +Primarily, progenitor cells play key roles in repairing and maintaining body tissues. During embryonic development, they significantly contribute to organogenesis, forming major organs. In adults, progenitor cells function as a repair system, replenishing lost cells in tissues like skin, blood, or the gut lining. Various types of progenitor cells have distinct roles; for instance, neuronal progenitor cells specialize into different brain cells, while myeloid progenitor cells develop into red and white blood cells and platelets. + +Disruptions to progenitor cells can lead to diseases, emphasizing their vital role in tissue homeostasis. Their unique properties also make them valuable in therapeutic approaches like tissue engineering and regenerative medicine. Researchers are exploring methods to direct these cells towards specific types to replace cells lost or damaged in conditions like spinal cord injuries, diabetes, and heart disease." https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/progenitor-cell|DOI:10.1155/2017/5217967|DOI:10.1038/s42003-023-04893-0|DOI:10.1900/RDS.2010.7.105|DOI:10.15171/jcvtr.2017.22 +767 CL:0011025 CL_0011025 "Exhausted T cells, or T cell exhaustion, represent a state of T lymphocytes characterized by diminished responses to antigenic stimulation and reduced proliferative immunity. Following prolonged exposure to antigens, such as in chronic viral infections or cancer, T cell exhaustion is a progressive loss of function that can lead to severe impairment of the immune response, potentially resulting in the deletion of the T cell population. + +A key feature of exhausted T cells involves the persistent coexpression of several inhibitory surface receptors commonly known as immune checkpoints. These checkpoints play a crucial role in regulating T-cell activity, allowing for the controlled suppression of immune responses following activation. Unlike effector or memory T cells that take part vigorously in the elimination of pathogenic agents and provide long-term immunity respectively, exhausted T cells express a range of inhibitory receptors, which dampen the immune response. Though intended to prevent immunopathology that might arise from uncontrolled T cell activation, this immune-suppressive function often plays into the hands of chronic viral infections and tumors, preventing the effective clearance of pathogens and malignant cells. + + +" DOI:10.1038/ni.2035|DOI:10.1111/j.1365-2567.2010.03255.x|DOI:10.1158/1078-0432.CCR-21-0206|DOI:10.1038/nri3862 +768 CL:0011024 CL_0011024 "Double-negative T regulatory cells (DN Tregs) are a distinct subset of immune cells identified by their lack of CD4 and CD8 surface markers, typical of conventional T cells. + +The primary role of DN Tregs is to modulate immune responses and maintain immune homeostasis by controlling the threshold of responsiveness. This prevents the risk of overreactions leading to conditions like autoimmunity. Their mechanism involves secreting anti-inflammatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta), inhibiting effector T cell function and potentially enhancing other regulatory T cells. + +Dysregulation or dysfunction of DN Tregs has been linked to autoimmune and inflammatory diseases, making them significant targets for therapeutic strategies. Ongoing studies also explore their role in cancer progression and control due to their immunosuppressive properties. " DOI:10.1093/jmcb/mjr043|DOI:10.1111/imr.12170|DOI:10.3389/fmed.2023.1244298|DOI:10.1080/21645515.2022.2035117 +769 CL:0011115 CL_0011115 "Precursor cells represent an intermediate stage between an undifferentiated stem cell and a fully specialized cell. + +Possessing the ability to differentiate into one or multiple specialized cell types, precursor cells exhibit partial stem cell characteristics. This differentiation is vital for various aspects of biological development and maintenance. Neural precursor cells, for example, can give rise to neurons, astrocytes, and oligodendrocytes, while hematopoietic precursor cells can transform into different blood cell types. This orchestrated process aligns with the body's metabolic activities, ensuring the production of the right cell types in response to physiological needs. + +Moreover, the study of precursor cells has become a promising field in regenerative medicine and cellular therapies. However, it's essential to note that precursor cells have a more limited self-renewal capacity compared to stem cells, and once they start differentiating along a specific cell lineage, the process is often irreversible." DOI:10.1016/S0076-6879(06)19007-2|https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/precursor-cell|DOI:10.1006/nbdi.1997.0137 +770 CL:0019003 CL_0019003 "Tracheobronchial goblet cells, named for their goblet-like shape, are specialized cells mainly found in the respiratory tract, including the trachea and bronchial tubes. Positioned among ciliated epithelial cells, they play a crucial role in the respiratory system's defense against particles and pathogens. + +These cells, akin to mucus-producing factories, secrete a viscous fluid primarily composed of mucin proteins. Their principal function is to create a protective layer over the respiratory tract's epithelial surfaces. This layer acts as the first line of defense by trapping dust, microbes, allergens, and foreign particles, preventing them from reaching the lungs' deeper, more sensitive areas. The mucus layer also supports proper cilia function and surface lubrication. + +In addition to their protective role, tracheobronchial goblet cells contribute to immune regulation in the lungs. When pathogens are detected, they signal specific immune cells to enhance the lung's immune response. However, conditions like chronic bronchitis, asthma, or cystic fibrosis may lead to goblet cell overproduction of mucus, potentially obstructing airways. + + + + + +" https://www.ncbi.nlm.nih.gov/books/NBK534789/|DOI:10.4161/tisb.24997|DOI:10.1172/JCI27690 +771 CL:0019018 CL_0019018 "Blood vessel smooth muscle cells, located in the walls of blood vessels, form a significant portion of the middle layer known as the tunica media. These cylindrical, interconnected cells create a resilient sheath around blood vessels, imparting contractility. + +Their primary role is regulating blood flow and pressure by controlling the contractile state of blood vessels. Contraction (vasoconstriction) reduces vessel diameter, elevating blood pressure, while relaxation (vasodilation) increases diameter, lowering blood pressure. + +Additionally, blood vessel smooth muscle cells are involved in the body's healing response to vascular injury; they can shift from a contractile state to a synthetic state where they proliferate and produce extracellular matrix proteins aiding in tissue repair. On the other hand, abnormal growth is linked to diseases like hypertension and atherosclerosis. + + + + + + + + +" https://www.ncbi.nlm.nih.gov/books/NBK470401/|https://www.ncbi.nlm.nih.gov/books/NBK557562/|https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3016065|DOI:10.1093/cvr/cvy023 +772 CL:1000453 CL_1000453 "Epithelial cells of intermediate tubule are cells found in the renal tubules, specifically within the nephron. Nephrons are the functional units of the kidneys responsible for filtering blood and producing urine. Each nephron consists of several parts, including a renal corpuscle (comprising the glomerulus and Bowman's capsule) and a renal tubule. The renal tubule is divided into several segments, including the proximal convoluted tubule, the loop of Henle, the distal convoluted tubule, and the collecting duct. The ""intermediate tubule"" refers to a portion of this tubule system, typically found between the proximal and distal convoluted tubules. + +The epithelial cells lining these tubules express proteins such as aquaporin 1 and urea transporter A2 which play crucial roles in reabsorption and secretion processes that help regulate the composition of urine. They are involved in the reabsorption of essential substances such as glucose, ions (e.g., sodium, potassium), and water, as well as the secretion of waste products and other substances into the urine. These cells have specialized structures and transport mechanisms to facilitate these functions, contributing to the kidney's ability to maintain fluid and electrolyte balance in the body. +" DOI:10.2147/IJNRD.S154000|DOI:10.1007/s00418-016-1434-7|DOI:10.1016/bs.mcb.2019.06.003 +773 CL:1000450 CL_1000450 "The epithelial cells of the glomerular capsule, which include podocytes and parietal epithelial cells, are an integral part of the kidney's filtration system. These specialized cells compose the outermost layer of the glomerulus, a network of small blood vessels called capillaries that play a vital role in the filtration of blood, removal of waste molecules, and retention of necessary proteins. + +Podocytes feature numerous extended arms or foot-like processes called pedicels, which embrace the glomerular capillaries. The pedicels of neighboring podocytes interlock, separating and rejoining around the glomerular capillaries to form a unique filtration obstruction, the filtration slit. These slits are covered by a thin, negatively charged diaphragm that acts as a second layer of filtration, permitting water and small-sized solutes to pass while prohibiting most proteins and larger molecules, thus maintaining blood composition balance. Parietal epithelial cells have their own unique functions that are critical to renal architecture and function. Moreover, these cells represent a reservoir of renal progenitors in adult human kidney which generate novel podocytes during childhood and adolescence, and can regenerate injured podocytes. + +Together, epithelial cells of the glomerular capsule significantly contribute to the filtration selectivity and permeability of the glomerular filtration barrier. Their ability to contract and relax allows for the control of the filtration rate of glomerular capillaries. Additionally, these cells can undergo dynamic structural modifications in response to various systemic and local stimuli, therefore adding to the adaptive potential of the kidney under different physiological and pathological conditions. " DOI:10.1159/000481633|DOI:10.1159/000313943|DOI:10.1007/s00441-017-2600-5|DOI:10.1038/s41573-021-00242-0 +774 +775 +776 +777 +778 +779 CL:0002057 CL_0002057 "CD14+ CD16- classical monocytes are a subtype of monocytes that form a crucial component of the human immune system. Emerging from the bone marrow and entering the bloodstream, these cells play central roles in immune responses and regulation of inflammation. They form the majority of circulating monocytes in the body, typically contributing to around 80-90% of the total monocyte pool. + +The primary function of these classical monocytes is to serve in the frontline of host defense against infections. They are primed to migrate to sites of infection, and they express pattern recognition receptors that help them identify and phagocytose pathogens, leading to their destruction. Classical monocytes also contribute to inflammation by producing several pro-inflammatory cytokines. + +In response to specific signals from tissues under pathological conditions, such as infection or injury, classical monocytes can leave the bloodstream and migrate towards the affected sites. Following their arrival, these cells differentiate into diverse cell types including macrophages and dendritic cells to combat specific pathogens or injury. Dysregulated monocyte activity can lead to the development of many human diseases including inflammation, infection, tissue injury, and various autoimmune diseases." DOI:10.1111/sji.12883|DOI:10.3389/fimmu.2015.00423/full|DOI:10.1182/blood-2009-07-235028|DOI:10.3389/fimmu.2019.02035|DOI:10.1038/nri.2017.28 +780 CL:0000956 CL_0000956 "The pre-B-I cell, also known as an early pre-B cell, is an integral step in the B cell development pathway in the bone marrow. These precursor B cells are characterized by expression of CD34 and surrogate immunoglobulin light chain (VpreB , Lambda 5 (mouse)/14.1 (human)) on the cell surface, as well as TdT, Rag1,and Rag2 intracellularly; they carry a D-JH DNA rearrangement, and lack expression of immunglobulin heavy chain protein. + +This cell type represents the stage subsequent to pro-B cells but precedes pre-B-II cells. At the pre-B-I cell stage, cells undergo VH to D-JH recombination. At this point, if the rearranged μ heavy chain can be produced and paired with a surrogate light chain, this can be expressed on the cell surface as the pre-B cell receptor (pre-BCR), forming the next stage of development, the pre-B-II cell. " DOI:10.4049/jimmunol.170.3.1354|DOI:10.1111/j.1600-065X.2000.imr017512.x|DOI:10.1016/j.it.2022.01.003|DOI:10.1016/j.febslet.2010.04.057 +781 CL:0002048 CL_0002048 "The late pro-B cell, also referred to as Hardy fraction C, is a late-stage progenitor cell in the progression of B cell development in the bone marrow. B cells are an essential part of humoral immunity, the component of the immune system that produces antibodies against pathogens. + +The pro-B cell developmental stage occurs in the bone marrow and is divided into early pro-B cell and late pro-B cell stages: first, early pro-B cells rearrange the short D (diversity) and J (joining) segments of the H-chain and become late pro-B cell, in which a second rearrangement combines an upstream selected V gene segment with the short DJ region. Successful in-frame rearrangement in the late pro-B cell leads to expression of Igμ and its assembly with the surrogate light chain and Igα and Igβ to form the pre-B cell receptor in large pre-B cells. +" DOI:10.1007/978-981-15-3532-1_1|DOI:10.1016/C2009-0-62217-0|DOI:10.1016/j.febslet.2010.04.057|DOI:10.1111/pai.13589|DOI:10.1084/jem.20221105 +782 CL:0002191 CL_0002191 "Granulocytopoietic cells represent a heterogeneous group of progenitor cells that give rise to the different types of granulocytes through a process called granulocytopoiesis. Granulocytopoietic cells include myeloblasts, myelocytes, basophil mast progenitors and other precursors, which develop into the variegated subtypes of granulocytes: neutrophils, eosinophils, and basophils, all of which perform distinct functions in immune responses. + +The primary function of granulocytopoietic cells is regeneration and development of granulocytes. They actively participate in hematopoiesis, the intricate process of blood cell production. Typically, these cells derive from multipotent hematopoietic stem cells (HSCs). Over time and under specific hereditary and environmental influences, they differentiate and mature into granulocyte cells. Spurred by physiological triggers, these precursor cells undergo a series of mitotic divisions and maturation processes, eventually turning into fully functional granulocytes, which play an instrumental role in the body's immune system: +Neutrophils provide a crucial line of defense against bacterial and fungal infections, racing to the scene of an infection where they perform phagocytosis- consuming invading organisms. Eosinophils are vital in tackling multicellular parasites and are involved in allergic reactions. Basophils, while less abundant, are involved in inflammatory reactions, particularly allergic responses, by releasing histamine and heparin. +" DOI:10.1016/B978-0-323-35775-3.00013-8|DOI:10.1016/B978-0-12-802900-8.00019-1|https://www.sciencedirect.com/topics/medicine-and-dentistry/granulopoiesis +783 CL:0002399 CL_0002399 "CD1c-positive myeloid dendritic cells represent one of the conventional myeloid dendritic cell subsets, which have been categorized based upon their expression of the cell surface markers CD1c and CD141. However, these markers have limitations as both may be expressed on multiple cell types. The more commonly accepted nomenclature of these cell types is conventional dendritic cell 1 (cDC1) for CD141+ dendritic cells and conventional dendritic cell 2 (cDC2) for CD1c+ dendritic cells. + +cDC2 cells are defined by high expression of the transcription factor IRF4 in addition to cell surface markers such as CD1c, CD11c, CD11b, and SIRPA, although the expression levels of different markers can vary across dendritic cells found in different tissues. cDC2 cells are the predominant population of myeloid or conventional dendritic cells in the body. They can be further subclassified into DC2 and DC3 cells, although the functional differences of these subsets are not well characterized. + +Dendritic cells are responsible for sensing antigens and presenting them to cells of the adaptive immune response to activate them. cDC2 cells can present glycolipid antigens in addition to protein antigens. cDC2 may also perform antigen cross-presentation, in which antigens derived from the extracellular environment may also be presented in the context of MHC I molecules, while typically intracellular antigens are presented in the context of MHC I molecules. cDC2 can also secrete a range of cytokines, such as IL-12, tumor necrosis factor-alpha, and IL-10, to further direct the immune response." DOI:10.1111/imm.12888|DOI:10.1016/bs.ircmb.2019.07.004|DOI:10.1016/j.coi.2013.11.002 +784 CL:0002394 CL_0002394 "CD141-positive myeloid dendritic cells represent one of the conventional myeloid dendritic cell subsets, which have been categorized based upon their expression of the cell surface markers CD1c and CD141. However, these markers have limitations as both may be expressed on multiple cell types. The more commonly accepted nomenclature of these cell types is conventional dendritic cell 1 (cDC1) for CD141+ dendritic cells and conventional dendritic cell 2 (cDC2) for CD1c+ dendritic cells. + +cDC1 cells are defined by high expression of the transcription factor IRF8 in addition to cell surface markers such as CD141, CLEC9A, and XCR1, although the expression levels of different markers can vary across dendritic cells found in different tissues. cDC1 cells are relatively rare compared to cDC2 cells. + +Dendritic cells are responsible for sensing antigens and presenting them to cells of the adaptive immune response to activate them. cDC1 appear to primarily perform antigen cross-presentation, in which antigens derived from the extracellular environment may also be presented in the context of MHC I molecules, while typically intracellular antigens are presented in the context of MHC I molecules. cDC1 can also secrete a range of cytokines, including type III interferons, to further direct the immune response. cDC1s are thus important for antitumor immunity and in viral and bacterial infections." DOI:10.1111/imm.12888|DOI:10.1016/bs.ircmb.2019.07.004|DOI:10.1016/j.coi.2013.11.002 +785 CL:0002465 CL_0002465 "CD11b-positive dendritic cells are a subset of conventional dendritic cells, which express the myeloid antigen CD11b. They play an important role in the recognition, uptake, processing, and presentation of antigens to T cells, thereby bridging innate and adaptive immunity. + +CD11b+ dendritic cells are the most abundant conventional dendritic cells in lymphoid organs (except for the thymus). Their MHC presentation and migration is dependent on IRF4, although the importance of IRF4 for the development of CD11b+ is still under debate. + +They represent a heterogeneous subset of dendritic cells, which includes epidermal Langerhans cells, dermal and interstitial dendritic cells. Given their heterogeneity, the specific functions of CD11b+ dendritic cells are difficult to assign. They exhibit strong expression of MHC-II presentation complexes and thereby play an important role in the induction of CD4+ T cell immunity. CD11b+ dendritic cells can also be characterized by their production of cytokines, such as IL-6 and IL-23, and splenic CD11b+ dendritic cells have been shown to produce proinflammatory chemokines, such as CCL3, CCL4, and CCL5, following TLR ligand exposure. +" DOI:10.1016/j.immuni.2014.04.016|DOI:10.1016/bs.ircmb.2019.07.004|DOI:10.1016/j.coi.2013.11.002|DOI:10.1146/annurev-immunol-020711-074950|DOI:10.3389/fimmu.2018.03176 +786 CL:4030002 CL_4030002 "Effector memory CD45RA-positive, alpha-beta T cells, or terminally-differentiated (TEMRA) cells, represent a unique sub-population of T cells, characterized by their ability to quickly respond to previously encountered antigens. These highly specialized cells are among the final stages of T cell differentiation, exhibiting both memory and effector characteristics. They express the CD45RA molecule on their surface, which is typically associated with naïve T cells, leading to them often being misidentified as such. However, unlike naïve T cells, TEMRA cells exhibit rapid effector function upon encountering an antigen. + +The primary function of TEMRA cells is to provide rapid immune responses to antigens that the organism has previously encountered. Unlike central memory T cells, which reside in the lymphoid organs and require time to proliferate, differentiate, and migrate to the site of infection, TEMRA cells can immediately respond to a threat. They circulate through peripheral tissues, constitutively expressing receptors that permit direct migration to inflamed tissues. Upon arrival they exert their effector functions, such as direct cell cytotoxicity or cytokine release, to aid in the removal of the pathogen. + +Moreover, TEMRA cells are unique for their increased cytotoxic capabilities when compared to other T cells. This is particularly important during viral infections, where rapid response is critical. The presence of this cell population in the peripheral blood has been associated with protective immunity against various viral and bacterial infections. In addition to defending against pathogens, these highly differentiated T lymphocytes also play a role in immunopathological disorders, where they can contribute to tissue damage. " DOI:10.1016/j.immuni.2018.01.007|DOI:10.1186/s13073-021-00918-7|DOI:10.1101/cshperspect.a037929|DOI:10.1182/blood-2005-11-007237 +787 CL:2000093 CL_2000093 "Bronchus fibroblasts of the lung are specialized stromal cells that are located in bronchus tissue and constitute the critical fibrous network that provides structural integrity to the lungs. These cells are pivotal for maintaining the bronchial extracellular matrix (ECM) via synthesis and regulation of diverse components of the ECM, including proteoglycans, collagen, and elastin. + +In response to lung injuries or during disease states such as chronic obstructive pulmonary disease (COPD) or pulmonary fibrosis, bronchus fibroblasts play an essential role in the wound healing process. They proliferate and differentiate into myofibroblasts, distinguishing themselves with the synthesis of alpha-smooth muscle actin (α-SMA). The migration, proliferation, and subsequent activity of myofibroblasts are key to wound contraction, scar formation and remodeling of the bronchial tree structure, vital for maintaining the functioning capacity of the lungs. + +Though beneficial for acute injury repair, excessive or dysregulated activity of bronchus fibroblasts can lead to pathological organ remodeling, contributing to fibrosing lung diseases. In these conditions, myofibroblasts persist in injured lung tissue, continuously producing ECM components that can eventually lead to scar formation, decreasing lung compliance, and impairing gas exchange. " DOI:10.1002/sctm.20-0526|DOI:10.1513/AnnalsATS.201406-240MG |DOI:10.1183/13993003.01805-2016|DOI:10.1513/pats.200708-146DR|DOI:10.1172/JCI93557 +788 CL:1000597 CL_1000597 "Papillary tips cells are specialized cells located in the renal papilla, the very tip of the renal pyramid in kidneys. They are crucial in the formation of nephrons, the functional units of the kidneys. Proper functioning of the nephrons, facilitated by papillary tips cells, ensures the body maintains homeostasis by filtering blood, metabolizing nutrients, reabsorbing necessary ions and nutrients back to the body, creating urine, and sending it to be excreted from the body. + +Their main function is related to urine concentration and regulation of electrolytes within the body. Papillary tips cells contribute to the mechanism of countercurrent multiplication, which derives a concentration gradient that enables the nephron to produce concentrated urine. In this process, these cells specifically regulate the water, sodium, potassium, calcium, and urea concentration in the urine. This helps in maintaining the body's acid-base balance and blood pressure. + +Papillary tips cells also play a vital role in the early stages of kidneys' development. During embryogenesis, they proliferate and grow to form the renal papilla, an integral part of kidney development. Such proliferation is regulated by the Wnt signaling pathway, a group of signal transduction pathways made up of proteins that pass signals into a cell through cell surface receptors. Thus, they have a distinct value in both maintaining physiological functions in a developed kidney and initial kidney formation during development. " DOI:10.1091/mbc.e03-06-0432|DOI:10.1016/j.ydbio.2011.02.019|DOI:10.1016/j.ekir.2016.12.007|DOI:10.1111/j.1748-1716.2011.02261.x +789 CL:1001045 CL_1001045 "The kidney cortex artery cells are a fundamental part of the renal vasculature system, specifically located within the outer portion of the kidney known as the renal cortex. These cells are critical players in kidney function and are integral to renal homeostasis. They are part of the arteries that supply the renal cortex with oxygenated blood, providing necessary support for kidney functioning. + +Kidney cortex artery cells, similar to other vascular cells, have a vital role in maintaining the structure and function of the arterial wall. Their inherent abilities for vasoconstriction and vasodilation regulate the blood flow to the kidneys. In addition to their role in blood supply, these cells are responsible for the production of various substances necessary for maintaining the balance of salts, fluids and other solutes within the body. +" DOI:10.1002/cphy.c120012|DOI:10.1681/ASN.2019080832|DOI:10.1152/ajprenal.00051.2003 +790 CL:1000453 CL_1000453 "Epithelial cells of intermediate tubule are cells found in the renal tubules, specifically within the nephron. Nephrons are the functional units of the kidneys responsible for filtering blood and producing urine. Each nephron consists of several parts, including a renal corpuscle (comprising the glomerulus and Bowman's capsule) and a renal tubule. The renal tubule is divided into several segments, including the proximal convoluted tubule, the loop of Henle, the distal convoluted tubule, and the collecting duct. The ""intermediate tubule"" refers to a portion of this tubule system, typically found between the proximal and distal convoluted tubules. + +The epithelial cells lining these tubules express proteins such as aquaporin 1 and urea transporter A2 which play crucial roles in reabsorption and secretion processes that help regulate the composition of urine. They are involved in the reabsorption of essential substances such as glucose, ions (e.g., sodium, potassium), and water, as well as the secretion of waste products and other substances into the urine. These cells have specialized structures and transport mechanisms to facilitate these functions, contributing to the kidney's ability to maintain fluid and electrolyte balance in the body. +" DOI:10.2147/IJNRD.S154000|DOI:10.1007/s00418-016-1434-7|DOI:10.1016/bs.mcb.2019.06.003 +791 CL:1000450 CL_1000450 "The epithelial cells of the glomerular capsule, which include podocytes and parietal epithelial cells, are an integral part of the kidney's filtration system. These specialized cells compose the outermost layer of the glomerulus, a network of small blood vessels called capillaries that play a vital role in the filtration of blood, removal of waste molecules, and retention of necessary proteins. + +Podocytes feature numerous extended arms or foot-like processes called pedicels, which embrace the glomerular capillaries. The pedicels of neighboring podocytes interlock, separating and rejoining around the glomerular capillaries to form a unique filtration obstruction, the filtration slit. These slits are covered by a thin, negatively charged diaphragm that acts as a second layer of filtration, permitting water and small-sized solutes to pass while prohibiting most proteins and larger molecules, thus maintaining blood composition balance. Parietal epithelial cells have their own unique functions that are critical to renal architecture and function. Moreover, these cells represent a reservoir of renal progenitors in adult human kidney which generate novel podocytes during childhood and adolescence, and can regenerate injured podocytes. + +Together, epithelial cells of the glomerular capsule significantly contribute to the filtration selectivity and permeability of the glomerular filtration barrier. Their ability to contract and relax allows for the control of the filtration rate of glomerular capillaries. Additionally, these cells can undergo dynamic structural modifications in response to various systemic and local stimuli, therefore adding to the adaptive potential of the kidney under different physiological and pathological conditions. " DOI:10.1159/000481633|DOI:10.1159/000313943|DOI:10.1007/s00441-017-2600-5|DOI:10.1007/s00441-017-2600-5 +792 CL:0000232 CL_0000232 "Erythrocytes, also known as red blood cells, are a type of specialized cell whose main function it is to transport oxygen from the lungs to the body's tissues and organs, and to transport carbon dioxide from the body's tissues to the lungs, where it can be exhaled out of the body. In humans, erythrocytes make up the largest percentage of cells in the body. Human erythrocytes are biconcave in shape and lack nuclei and organelles, allowing them to carry oxygen and carbon dioxide through the bloodstream more efficiently. Most mammals have enucleated erythrocytes, while other animals such as birds and reptiles have nucleated erythrocytes. + +Hemoglobin, a protein located inside erythrocytes, is responsible for binding to oxygen. Erythrocytes are produced in the bone marrow and have a lifespan of approximately 120 days before they are broken down and recycled by the body. Erythrocytes are regulated by the hormone erythropoietin, which is produced by the kidneys and liver in response to low oxygen levels in the body, thereby stimulating erythrocyte production . In addition to their role in oxygen transport, erythrocytes also play a key role in regulating the body's pH levels. Without erythrocytes, oxygen would not be able to be transported efficiently throughout the body and tissues would not receive the necessary oxygen to function properly. Overall, erythrocytes are essential for maintaining the health and homeostasis of the body. +" DOI:10.1056/NEJM199801223380407|DOI:10.3389/fphys.2021.655393|DOI:10.1016/j.blre.2012.12.003 +793 CL:0000860 CL_0000860 "Classical monocytes are a subtype of monocytes in humans are characterized by high CD14 but no CD16 expression. Emerging from the bone marrow and entering the bloodstream, these cells play central roles in immune responses and regulation of inflammation. CD14-positive CD16-negative monocytes form the majority of circulating monocytes in the body, typically contributing to around 80-90% of the total monocyte pool. In mice, classical monocytes are characterized by high expression levels of the Gr1 cell surface marker. + +The primary function of the classical monocytes is to serve in the frontline of host defense against infections. They are primed to migrate to sites of infection, and they express pattern recognition receptors that help them identify and phagocytose pathogens, leading to their destruction. Classical monocytes also contribute to inflammation by producing several pro-inflammatory cytokines including interleukins and tumor necrosis factors. + +In response to specific signals from tissues under pathological conditions, such as infection or injury, classical monocytes can leave the bloodstream and migrate towards the affected sites. Following their arrival, these cells differentiate into diverse cell types including macrophages and dendritic cells to combat specific pathogens or injury. Dysregulated monocyte activity can lead to the development of many human diseases including inflammation, infection, tissue injury, and various autoimmune diseases. +" DOI:10.1111/sji.12883|DOI:10.3389/fimmu.2015.00423/full|DOI:10.1182/blood-2009-07-235028|DOI:10.3389/fimmu.2019.02035|DOI:10.1038/nri.2017.28 +794 CL:0000177 CL_0000177 "Testosterone-secreting cells are specialized cells found primarily in the testes and ovaries of mammals. In males, the main cell type secreting testosterone are Leydig cells, which are named after the German anatomist Franz von Leydig who discovered them in 1850. These cells constitute a critical component within the male reproductive system and are interspersed between the seminiferous tubules where sperm production occurs. In females, most testosterone is produced by Theca cells in the ovaries. Small quantities of testosterone are also produced by the adrenal glands in both sexes. + +In males, Leydig cells are fundamental for the biosynthesis and secretion of testosterone. The release of luteinizing hormone (LH) from the anterior pituitary gland stimulates Leydig cells to produce and secrete testosterone. In response to LH, Leydig cells convert cholesterol into testosterone, which then plays a crucial role in the development and maintenance of primary and secondary male sexual characteristics. These include the formation and maturation of male reproductive organs, onset of spermatogenesis, and the presentation of male secondary sexual traits such as the deepening of the voice, growth of facial hair, development of muscles, and a broadening of shoulders. Apart from testosterone production, Leydig cells also secrete insulin-like factor 3 (INSL3) that is essential for testicular descent during embryonic development in males. Dysregulation or loss of Leydig cells can lead to numerous conditions like testosterone deficiency, infertility, and certain forms of testicular cancer. + +The Theca cells of female mammals are specialized stromal cells found within the ovarian follicles. The two forms, theca interna cells and theca externa cells, both playing significant roles in ovarian function and the reproductive system as a whole. Found in all mammalian species, these cells are involved in intricate processes like ovulation. Synthesis of testosterone of thecal cells in the ovary is driven by LH stimulation; testosterone formed by the thecal cells in response to LH stimulation is converted in the granulosa cell to estradiol, a process that is also dependent on follicle-stimulating hormone (FSH). In women, testosterone plays an important physiologic role in reproductive tissues and muscle, as well as mood and cognition. +" https://www.ncbi.nlm.nih.gov/books/NBK526128/|DOI:10.1016/j.mce.2017.06.026|DOI:10.3389/fendo.2022.1017468|DOI:10.1093/biolre/ioy059|DOI:10.3389/fendo.2014.00006 diff --git a/src/patterns/data/source_data/CellGuide/CG_desc_proc.py b/src/patterns/data/source_data/CellGuide/CG_desc_proc.py new file mode 100644 index 000000000..7dbcd88ef --- /dev/null +++ b/src/patterns/data/source_data/CellGuide/CG_desc_proc.py @@ -0,0 +1,20 @@ +import pandas as pd +cg_desc = pd.read_excel('./CellGuide Validated Descriptions for CL Review.xlsx') +cg_desc.fillna('', inplace=True) +rows = [] +for i,r in cg_desc.iterrows(): + if not (r['For CL inclusion'] == 1): + next + row = {'defined_class': r['CL ID'], 'CL_short_form': str(r['CL ID']).replace(':', '_'), + 'desc': r["Final version (QC'd)"], 'pubs': ''} + pub_list = [] + for k,v in r.items(): + if str(k).startswith('Supporting'): + if str(v).startswith('http'): + pub_list.append(v) + elif(v): + pub_list.append('DOI:' + v) + row['pubs'] = '|'.join(pub_list) + rows.append(row) +out = pd.DataFrame.from_records(rows) +out.to_csv('../../default/ExtendedDescription.tsv', sep='\t') \ No newline at end of file diff --git a/src/patterns/data/source_data/CellGuide/CellGuide Validated Descriptions for CL Review.xlsx b/src/patterns/data/source_data/CellGuide/CellGuide Validated Descriptions for CL Review.xlsx new file mode 100644 index 0000000000000000000000000000000000000000..bb8c23874347438cb74a0c49cd191628cc3aa268 GIT binary patch literal 647956 zcmeEugFA^0gi%538-{P2!cq7^ia|vLw73OC@9@EG*Z%C(jqyexox{*W z^X>6@-*cYlm2>`q^YPoidv1n-wbxqLx>npk(EV+ArkY6)Y^& zH7qP5tm{|bh}zmX7~44Ls<^&2wui8}SX({JxOSECGuBn$^Z)Qt>~C}cpUvFKn8#c_Wluvo*|%2*WFp~*OYKcepolq9-+4BLd;x=c?sjMq9 z99WlIT(jQe9yY`LuQ?6ZGCaIq=2wD$kg~`waT5)zzd5y^E`oj=>;RDy2IBGJ0vqe~ zKO(hCm4jvvfS)W7h_`@9)wMIWvS(+*tp7hk{||@d-&8M*l2d5q!1qH*o%(m7N2en0 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