Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
107-423: Other animal coverings , such as the arthropod exoskeleton , have different developmental origin , structure and chemical composition . The adjective cutaneous means "of the skin" (from Latin cutis 'skin'). In mammals , the skin is an organ of the integumentary system made up of multiple layers of ectodermal tissue and guards the underlying muscles , bones , ligaments , and internal organs . Skin of
214-442: A mesendodermal fate, with Oct4 actively suppressing genes associated with a neural ectodermal fate. Similarly, increased levels of Sox2 and decreased levels of Oct4 promote differentiation towards a neural ectodermal fate, with Sox2 inhibiting differentiation towards a mesendodermal fate. Regardless of the lineage cells differentiate down, suppression of NANOG has been identified as a necessary prerequisite for differentiation. In
321-455: A purine analog, has proven to induce dedifferentiation in myotubes . These manifestly dedifferentiated cells—now performing essentially as stem cells—could then redifferentiate into osteoblasts and adipocytes . Each specialized cell type in an organism expresses a subset of all the genes that constitute the genome of that species . Each cell type is defined by its particular pattern of regulated gene expression . Cell differentiation
428-447: A stratum germinativum and stratum corneum , but the other intermediate layers found in humans are not always distinguishable. Hair is a distinctive feature of mammalian skin, while feathers are (at least among living species) similarly unique to birds . Birds and reptiles have relatively few skin glands , although there may be a few structures for specific purposes, such as pheromone -secreting cells in some reptiles , or
535-658: A cell's size, shape, membrane potential , metabolic activity , and responsiveness to signals. These changes are largely due to highly controlled modifications in gene expression and are the study of epigenetics . With a few exceptions, cellular differentiation almost never involves a change in the DNA sequence itself. Metabolic composition, however, gets dramatically altered where stem cells are characterized by abundant metabolites with highly unsaturated structures whose levels decrease upon differentiation. Thus, different cells can have very different physical characteristics despite having
642-406: A conformational change in the receptor. The shape of the cytoplasmic domain of the receptor changes, and the receptor acquires enzymatic activity. The receptor then catalyzes reactions that phosphorylate other proteins, activating them. A cascade of phosphorylation reactions eventually activates a dormant transcription factor or cytoskeletal protein, thus contributing to the differentiation process in
749-418: A cylindrical shape. When the ducts mature and fill with fluid, the base of the ducts become swollen due to the pressure from the inside. This causes the epidermal layer to form a pit like opening on the surface of the duct in which the inner fluid will be secreted in an upwards fashion. The intercalary region of granular glands is more developed and mature in comparison with mucous glands. This region resides as
856-462: A different functionality for amphibians than granular. Mucous glands cover the entire surface area of the amphibian body and specialize in keeping the body lubricated. There are many other functions of the mucous glands such as controlling the pH, thermoregulation, adhesive properties to the environment, anti-predator behaviors (slimy to the grasp), chemical communication, even anti-bacterial/viral properties for protection against pathogens. The ducts of
963-510: A different nature exists in amphibians , reptiles , and birds . Skin (including cutaneous and subcutaneous tissues) plays crucial roles in formation, structure, and function of extraskeletal apparatus such as horns of bovids (e.g., cattle) and rhinos, cervids' antlers, giraffids' ossicones, armadillos' osteoderm, and os penis / os clitoris . All mammals have some hair on their skin, even marine mammals like whales , dolphins , and porpoises that appear to be hairless. The skin interfaces with
1070-430: A few closely related cell types. Finally, unipotent cells can differentiate into only one cell type, but are capable of self-renewal . In cytopathology , the level of cellular differentiation is used as a measure of cancer progression. " Grade " is a marker of how differentiated a cell in a tumor is. Three basic categories of cells make up the mammalian body: germ cells , somatic cells , and stem cells . Each of
1177-659: A hollow sphere of cells, called a blastocyst . The blastocyst has an outer layer of cells, and inside this hollow sphere, there is a cluster of cells called the inner cell mass . The cells of the inner cell mass go on to form virtually all of the tissues of the human body. Although the cells of the inner cell mass can form virtually every type of cell found in the human body, they cannot form an organism. These cells are referred to as pluripotent . Pluripotent stem cells undergo further specialization into multipotent progenitor cells that then give rise to functional cells. Examples of stem and progenitor cells include: A pathway that
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#17327723618591284-854: A large extent, differences in transcription factor binding are determined by the chromatin accessibility of their binding sites through histone modification and/or pioneer factors . In particular, it is important to know whether a nucleosome is covering a given genomic binding site or not. This can be determined using a chromatin immunoprecipitation assay. DNA-nucleosome interactions are characterized by two states: either tightly bound by nucleosomes and transcriptionally inactive, called heterochromatin , or loosely bound and usually, but not always, transcriptionally active, called euchromatin . The epigenetic processes of histone methylation and acetylation, and their inverses demethylation and deacetylation primarily account for these changes. The effects of acetylation and deacetylation are more predictable. An acetyl group
1391-458: A modified intercalary region (depending on the function of the glands), yet the majority share the same structure. The alveolar or mucous glands are much more simple and only consist of an epithelium layer as well as connective tissue which forms a cover over the gland. This gland lacks a tunica propria and appears to have delicate and intricate fibers which pass over the gland's muscle and epithelial layers. The epidermis of birds and reptiles
1498-473: A more specialized type. Differentiation happens multiple times during the development of a multicellular organism as it changes from a simple zygote to a complex system of tissues and cell types. Differentiation continues in adulthood as adult stem cells divide and create fully differentiated daughter cells during tissue repair and during normal cell turnover. Some differentiation occurs in response to antigen exposure. Differentiation dramatically changes
1605-416: A numerous individual mucus -secreting skin cells that aid in insulation and protection, but may also have poison glands , photophores , or cells that produce a more watery, serous fluid. In amphibians , the mucous cells are gathered together to form sac-like glands . Most living amphibians also possess granular glands in the skin, that secrete irritating or toxic compounds. Although melanin
1712-435: A regular pattern. Sonic hedgehog-expressing epidermal cells induce the condensation of cells in the mesoderm . The clusters of mesodermal cells signal back to the epidermis to form the appropriate structure for that position. BMP signals from the epidermis inhibit the formation of placodes in nearby ectoderm. It is believed that the mesoderm defines the pattern. The epidermis instructs the mesodermal cells to condense and then
1819-399: A ring of cells surrounding the basal portion of the duct which are argued to have an ectodermal muscular nature due to their influence over the lumen (space inside the tube) of the duct with dilation and constriction functions during secretions. The cells are found radially around the duct and provide a distinct attachment site for muscle fibers around the gland's body. The gland alveolus is
1926-429: A sac that is divided into three specific regions/layers. The outer layer or tunica fibrosa is composed of densely packed connective-tissue which connects with fibers from the spongy intermediate layer where elastic fibers, as well as nerves, reside. The nerves send signals to the muscles as well as the epithelial layers. Lastly, the epithelium or tunica propria encloses the gland. Mucous glands are non-venomous and offer
2033-432: A small number of genes, including OCT4 and NANOG, are methylated and their promoters repressed to prevent their further expression. Consistently, DNA methylation-deficient embryonic stem cells rapidly enter apoptosis upon in vitro differentiation. While the DNA sequence of most cells of an organism is the same, the binding patterns of transcription factors and the corresponding gene expression patterns are different. To
2140-451: A soft matrix without the use of diffusing factors. The stem-cell properties appear to be linked to tension in the cells' actin network. One identified mechanism for matrix-induced differentiation is tension-induced proteins, which remodel chromatin in response to mechanical stretch. The RhoA pathway is also implicated in this process. A billion-years-old, likely holozoan , protist , Bicellum brasieri with two types of cells, shows that
2247-415: A thin sheet of fibers called the basement membrane , which is made through the action of both tissues . The basement membrane controls the traffic of the cells and molecules between the dermis and epidermis but also serves, through the binding of a variety of cytokines and growth factors , as a reservoir for their controlled release during physiological remodeling or repair processes. The dermis
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#17327723618592354-847: Is Wnt signaling pathway . The Wnt pathway is involved in all stages of differentiation, and the ligand Wnt3a can substitute for the overexpression of c-Myc in the generation of induced pluripotent stem cells. On the other hand, disruption of β-catenin , a component of the Wnt signaling pathway, leads to decreased proliferation of neural progenitors. Growth factors comprise the second major set of candidates of epigenetic regulators of cellular differentiation. These morphogens are crucial for development, and include bone morphogenetic proteins , transforming growth factors (TGFs), and fibroblast growth factors (FGFs). TGFs and FGFs have been shown to sustain expression of OCT4, SOX2, and NANOG by downstream signaling to Smad proteins. Depletion of growth factors promotes
2461-442: Is chitin , a polysaccharide composed of N -acetylglucosamine units, together with proteins and lipids. The proteins and chitin are cross-linked. The rigidity is a function of the types of proteins and the quantity of chitin. It is believed that the epidermal cells produce protein and also monitors the timing and amount of protein to be incorporated into the cuticle. Often, in the cuticle of arthropods , structural coloration
2568-401: Is associated with gene activation, whereas trimethylation of lysine 27 on histone 3 represses genes During differentiation, stem cells change their gene expression profiles. Recent studies have implicated a role for nucleosome positioning and histone modifications during this process. There are two components of this process: turning off the expression of embryonic stem cell (ESC) genes, and
2675-424: Is based on mechanical signalling by the cytoskeleton using Embryonic differentiation waves . The mechanical signal is then epigenetically transduced via signal transduction systems (of which specific molecules such as Wnt are part) to result in differential gene expression. In summary, the role of signaling in the epigenetic control of cell fate in mammals is largely unknown, but distinct examples exist that indicate
2782-438: Is closer to that of mammals , with a layer of dead keratin-filled cells at the surface, to help reduce water loss. A similar pattern is also seen in some of the more terrestrial amphibians such as toads . In these animals, there is no clear differentiation of the epidermis into distinct layers, as occurs in humans , with the change in cell type being relatively gradual. The mammalian epidermis always possesses at least
2889-555: Is either added to or removed from the positively charged Lysine residues in histones by enzymes called histone acetyltransferases or histone deactylases , respectively. The acetyl group prevents Lysine's association with the negatively charged DNA backbone. Methylation is not as straightforward, as neither methylation nor demethylation consistently correlate with either gene activation or repression. However, certain methylations have been repeatedly shown to either activate or repress genes. The trimethylation of lysine 4 on histone 3 (H3K4Me3)
2996-407: Is found in the skin of many species, in the reptiles , the amphibians , and fish , the epidermis is often relatively colorless. Instead, the color of the skin is largely due to chromatophores in the dermis , which, in addition to melanin, may contain guanine or carotenoid pigments . Many species, such as chameleons and flounders may be able to change the color of their skin by adjusting
3103-408: Is guided by the cell adhesion molecules consisting of four amino acids, arginine , glycine , asparagine , and serine , is created as the cellular blastomere differentiates from the single-layered blastula to the three primary layers of germ cells in mammals, namely the ectoderm , mesoderm and endoderm (listed from most distal (exterior) to proximal (interior)). The ectoderm ends up forming
3210-420: Is involved in the proliferation and self-renewal of stem cells. Finally, Sonic hedgehog , in addition to its role as a morphogen, promotes embryonic stem cell differentiation and the self-renewal of somatic stem cells. The problem, of course, is that the candidacy of these signaling pathways was inferred primarily on the basis of their role in development and cellular differentiation. While epigenetic regulation
3317-561: Is maintained as a stem cell layer through an autocrine signal, TGF alpha , and through paracrine signaling from FGF7 ( keratinocyte growth factor ) produced by the dermis below the basal cells. In mice, over-expression of these factors leads to an overproduction of granular cells and thick skin. Hair and feathers are formed in a regular pattern and it is believed to be the result of a reaction-diffusion system. This reaction-diffusion system combines an activator, Sonic hedgehog , with an inhibitor, BMP4 or BMP2, to form clusters of cells in
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3424-532: Is necessary for driving cellular differentiation, they are certainly not sufficient for this process. Direct modulation of gene expression through modification of transcription factors plays a key role that must be distinguished from heritable epigenetic changes that can persist even in the absence of the original environmental signals. Only a few examples of signaling pathways leading to epigenetic changes that alter cell fate currently exist, and we will focus on one of them. Expression of Shh (Sonic hedgehog) upregulates
3531-549: Is observed, produced by nanostructures. In the mealworm beetle, Tenebrio molitor , cuticular color may suggest pathogen resistance in that darker individuals are more resistant to pathogens compared to more tan individuals. In botany , plant cuticles are protective, hydrophobic, waxy coverings produced by the epidermal cells of leaves, young shoots and all other aerial plant organs. Cuticles minimize water loss and effectively reduce pathogen entry due to their waxy secretion. The main structural components of plant cuticles are
3638-417: Is often controlled by cell signaling . Many of the signal molecules that convey information from cell to cell during the control of cellular differentiation are called growth factors . Although the details of specific signal transduction pathways vary, these pathways often share the following general steps. A ligand produced by one cell binds to a receptor in the extracellular region of another cell, inducing
3745-425: Is one term used for the outer layer of tissue of a mushroom 's basidiocarp , or "fruit body". The alternative term " pileipellis ", Latin for "skin" of a "cap" (meaning "mushroom" ) might be technically preferable, but is perhaps too cumbersome for popular use. It is the part removed in "peeling" mushrooms. On the other hand, some morphological terminology in mycology makes finer distinctions, such as described in
3852-545: Is termed a "bivalent domain" and rendering these genes sensitive to rapid induction or repression. Regulation of gene expression is further achieved through DNA methylation, in which the DNA methyltransferase -mediated methylation of cytosine residues in CpG dinucleotides maintains heritable repression by controlling DNA accessibility. The majority of CpG sites in embryonic stem cells are unmethylated and appear to be associated with H3K4me3-carrying nucleosomes. Upon differentiation,
3959-463: Is the extent and complexity of the role of epigenetic processes in the determination of cell fate. A clear answer to this question can be seen in the 2011 paper by Lister R, et al. on aberrant epigenomic programming in human induced pluripotent stem cells . As induced pluripotent stem cells (iPSCs) are thought to mimic embryonic stem cells in their pluripotent properties, few epigenetic differences should exist between them. To test this prediction,
4066-489: Is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis provides tensile strength and elasticity to the skin through an extracellular matrix composed of collagen fibrils , microfibrils , and elastic fibers , embedded in hyaluronan and proteoglycans . Skin proteoglycans are varied and have very specific locations. For example, hyaluronan , versican and decorin are present throughout
4173-461: Is thus a transition of a cell from one cell type to another and it involves a switch from one pattern of gene expression to another. Cellular differentiation during development can be understood as the result of a gene regulatory network . A regulatory gene and its cis-regulatory modules are nodes in a gene regulatory network; they receive input and create output elsewhere in the network. The systems biology approach to developmental biology emphasizes
4280-428: Is used in general parlance, and even by medical professionals, to refer to the thickened layer of skin surrounding fingernails and toenails (the eponychium ), and to refer to the superficial layer of overlapping cells covering the hair shaft ( cuticula pili ), consisting of dead cells, that locks the hair into its follicle . It can also be used as a synonym for the epidermis , the outer layer of skin. In zoology ,
4387-428: The dermis provide nourishment and waste removal from its own cells as well as for the epidermis . Dermis and subcutaneous tissues are thought to contain germinative cells involved in formation of horns, osteoderm, and other extra-skeletal apparatus in mammals. The dermis is tightly connected to the epidermis through a basement membrane and is structurally divided into two areas: a superficial area adjacent to
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4494-484: The epigenome , and the majority of current knowledge about the subject consists of speculations on plausible candidate regulators of epigenetic remodeling. We will first discuss several major candidates thought to be involved in the induction and maintenance of both embryonic stem cells and their differentiated progeny, and then turn to one example of specific signaling pathways in which more direct evidence exists for its role in epigenetic change. The first major candidate
4601-479: The invertebrate cuticle or cuticula is a multi-layered structure outside the epidermis of many invertebrates, notably arthropods and roundworms , in which it forms an exoskeleton (see arthropod exoskeleton ). The main structural components of the nematode cuticle are proteins , highly cross-linked collagens and specialised insoluble proteins known as "cuticlins", together with glycoproteins and lipids . The main structural component of arthropod cuticle
4708-399: The skull , these scales are lost in tetrapods , although many reptiles do have scales of a different kind, as do pangolins . Cartilaginous fish have numerous tooth-like denticles embedded in their skin, in place of true scales . Sweat glands and sebaceous glands are both unique to mammals , but other types of skin gland are found in other vertebrates . Fish typically have
4815-402: The uropygial gland of most birds. Cutaneous structures arise from the epidermis and include a variety of features such as hair, feathers, claws and nails. During embryogenesis, the epidermis splits into two layers: the periderm (which is lost) and the basal layer . The basal layer is a stem cell layer and through asymmetrical divisions, becomes the source of skin cells throughout life. It
4922-443: The activation of cell fate genes. Lysine specific demethylase 1 ( KDM1A ) is thought to prevent the use of enhancer regions of pluripotency genes, thereby inhibiting their transcription. It interacts with Mi-2/NuRD complex (nucleosome remodelling and histone deacetylase) complex, giving an instance where methylation and acetylation are not discrete and mutually exclusive, but intertwined processes. A final question to ask concerns
5029-400: The alveolar gland (sac). Structurally, the duct is derived via keratinocytes and passes through to the surface of the epidermal or outer skin layer thus allowing external secretions of the body. The gland alveolus is a sac-shaped structure that is found on the bottom or base region of the granular gland. The cells in this sac specialize in secretion. Between the alveolar gland and the duct is
5136-400: The amphibians. They are located in clusters differing in concentration depending on amphibian taxa. The toxins can be fatal to most vertebrates or have no effect against others. These glands are alveolar meaning they structurally have little sacs in which venom is produced and held before it is secreted upon defensive behaviors. Structurally, the ducts of the granular gland initially maintain
5243-560: The approximately 37.2 trillion (3.72x10 ) cells in an adult human has its own copy or copies of the genome except certain cell types , such as red blood cells , that lack nuclei in their fully differentiated state. Most cells are diploid ; they have two copies of each chromosome . Such cells, called somatic cells, make up most of the human body, such as skin and muscle cells. Cells differentiate to specialize for different functions. Germ line cells are any line of cells that give rise to gametes —eggs and sperm—and thus are continuous through
5350-415: The article on the " pileipellis ". Be that as it may, the pileipellis (or "peel") is distinct from the trama , the inner fleshy tissue of a mushroom or similar fruiting body, and also from the spore -bearing tissue layer, the hymenium . Cell differentiation Cellular differentiation is the process in which a stem cell changes from one type to a differentiated one. Usually, the cell changes to
5457-688: The authors conducted whole-genome profiling of DNA methylation patterns in several human embryonic stem cell (ESC), iPSC, and progenitor cell lines. Female adipose cells, lung fibroblasts , and foreskin fibroblasts were reprogrammed into induced pluripotent state with the OCT4 , SOX2 , KLF4 , and MYC genes. Patterns of DNA methylation in ESCs, iPSCs, somatic cells were compared. Lister R, et al. observed significant resemblance in methylation levels between embryonic and induced pluripotent cells. Around 80% of CG dinucleotides in ESCs and iPSCs were methylated,
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#17327723618595564-417: The authors discovered 1175 regions of differential CG dinucleotide methylation between at least one ES or iPS cell line. By comparing these regions of differential methylation with regions of cytosine methylation in the original somatic cells, 44-49% of differentially methylated regions reflected methylation patterns of the respective progenitor somatic cells, while 51-56% of these regions were dissimilar to both
5671-429: The body. Microorganisms like Staphylococcus epidermidis colonize the skin surface. The density of skin flora depends on region of the skin. The disinfected skin surface gets recolonized from bacteria residing in the deeper areas of the hair follicle , gut and urogenital openings. The epidermis of fish and of most amphibians consists entirely of live cells , with only minimal quantities of keratin in
5778-488: The cell to pull against the matrix at focal adhesions, which triggers a cellular mechano-transducer to generate a signal to be informed what force is needed to deform the matrix. To determine the key players in matrix-elasticity-driven lineage specification in MSCs, different matrix microenvironments were mimicked. From these experiments, it was concluded that focal adhesions of the MSCs were the cellular mechano-transducer sensing
5885-485: The cell's final function (e.g. myosin and actin for a muscle cell). Differentiation may continue to occur after terminal differentiation if the capacity and functions of the cell undergo further changes. Among dividing cells, there are multiple levels of cell potency , which is the cell's ability to differentiate into other cell types. A greater potency indicates a larger number of cell types that can be derived. A cell that can differentiate into all cell types, including
5992-410: The cells of the superficial layer. It is generally permeable, and in the case of many amphibians , may actually be a major respiratory organ. The dermis of bony fish typically contains relatively little of the connective tissue found in tetrapods . Instead, in most species, it is largely replaced by solid, protective bony scales . Apart from some particularly large dermal bones that form parts of
6099-411: The cellular mechanisms underlying these switches, in animal species these are very different from the well-characterized gene regulatory mechanisms of bacteria , and even from those of the animals' closest unicellular relatives . Specifically, cell differentiation in animals is highly dependent on biomolecular condensates of regulatory proteins and enhancer DNA sequences. Cellular differentiation
6206-434: The decision to adopt a stem, progenitor, or mature cell fate This section will focus primarily on mammalian stem cells . In systems biology and mathematical modeling of gene regulatory networks, cell-fate determination is predicted to exhibit certain dynamics, such as attractor-convergence (the attractor can be an equilibrium point, limit cycle or strange attractor ) or oscillatory. The first question that can be asked
6313-416: The dermis and epidermis extracellular matrix , whereas biglycan and perlecan are only found in the epidermis. It harbors many mechanoreceptors (nerve endings) that provide the sense of touch and heat through nociceptors and thermoreceptors . It also contains the hair follicles , sweat glands , sebaceous glands , apocrine glands , lymphatic vessels and blood vessels . The blood vessels in
6420-761: The differences of the matrix elasticity. The non-muscle myosin IIa-c isoforms generates the forces in the cell that lead to signaling of early commitment markers. Nonmuscle myosin IIa generates the least force increasing to non-muscle myosin IIc. There are also factors in the cell that inhibit non-muscle myosin II, such as blebbistatin . This makes the cell effectively blind to the surrounding matrix. Researchers have achieved some success in inducing stem cell-like properties in HEK 239 cells by providing
6527-554: The differentiated phenotype. Simultaneously, differentiation and development-promoting genes are activated by Trithorax group (TrxG) chromatin regulators and lose their repression. TrxG proteins are recruited at regions of high transcriptional activity, where they catalyze the trimethylation of histone H3 lysine 4 ( H3K4me3 ) and promote gene activation through histone acetylation. PcG and TrxG complexes engage in direct competition and are thought to be functionally antagonistic, creating at differentiation and development-promoting loci what
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#17327723618596634-648: The differentiation of ESCs, while genes with bivalent chromatin can become either more restrictive or permissive in their transcription. Several other signaling pathways are also considered to be primary candidates. Cytokine leukemia inhibitory factors are associated with the maintenance of mouse ESCs in an undifferentiated state. This is achieved through its activation of the Jak-STAT3 pathway, which has been shown to be necessary and sufficient towards maintaining mouse ESC pluripotency. Retinoic acid can induce differentiation of human and mouse ESCs, and Notch signaling
6741-504: The environment and is the first line of defense from external factors. For example, the skin plays a key role in protecting the body against pathogens and excessive water loss. Its other functions are insulation , temperature regulation , sensation, and the production of vitamin D folates. Severely damaged skin may heal by forming scar tissue . This is sometimes discoloured and depigmented. The thickness of skin also varies from location to location on an organism. In humans, for example,
6848-408: The epidermis, called the papillary region , and a deep thicker area known as the reticular region . The papillary region is composed of loose areolar connective tissue . This is named for its fingerlike projections called papillae that extend toward the epidermis . The papillae provide the dermis with a "bumpy" surface that interdigitates with the epidermis, strengthening the connection between
6955-401: The first two of which are used in induced pluripotent stem cell (iPSC) reprogramming, along with Klf4 and c-Myc – are highly expressed in undifferentiated embryonic stem cells and are necessary for the maintenance of their pluripotency . It is thought that they achieve this through alterations in chromatin structure, such as histone modification and DNA methylation, to restrict or permit
7062-483: The following functions: Skin is a soft tissue and exhibits key mechanical behaviors of these tissues. The most pronounced feature is the J-curve stress strain response, in which a region of large strain and minimal stress exists and corresponds to the microstructural straightening and reorientation of collagen fibrils. In some cases the intact skin is prestreched, like wetsuits around the diver's body, and in other cases
7169-417: The formation of an extracellular matrix and provide mechanical strength to the skin. Keratinocytes from the stratum corneum are eventually shed from the surface ( desquamation ). The epidermis contains no blood vessels , and cells in the deepest layers are nourished by diffusion from blood capillaries extending to the upper layers of the dermis . The epidermis and dermis are separated by
7276-641: The former mechanism, distinct daughter cells are created during cytokinesis because of an uneven distribution of regulatory molecules in the parent cell; the distinct cytoplasm that each daughter cell inherits results in a distinct pattern of differentiation for each daughter cell. A well-studied example of pattern formation by asymmetric divisions is body axis patterning in Drosophila . RNA molecules are an important type of intracellular differentiation control signal. The molecular and genetic basis of asymmetric cell divisions has also been studied in green algae of
7383-557: The generations. Stem cells, on the other hand, have the ability to divide for indefinite periods and to give rise to specialized cells. They are best described in the context of normal human development. Development begins when a sperm fertilizes an egg and creates a single cell that has the potential to form an entire organism. In the first hours after fertilization, this cell divides into identical cells. In humans, approximately four days after fertilization and after several cycles of cell division, these cells begin to specialize, forming
7490-453: The genus Volvox , a model system for studying how unicellular organisms can evolve into multicellular organisms. In Volvox carteri , the 16 cells in the anterior hemisphere of a 32-cell embryo divide asymmetrically, each producing one large and one small daughter cell. The size of the cell at the end of all cell divisions determines whether it becomes a specialized germ or somatic cell. Since each cell, regardless of cell type, possesses
7597-484: The importance of investigating how developmental mechanisms interact to produce predictable patterns ( morphogenesis ). However, an alternative view has been proposed recently . Based on stochastic gene expression, cellular differentiation is the result of a Darwinian selective process occurring among cells. In this frame, protein and gene networks are the result of cellular processes and not their cause. While evolutionarily conserved molecular processes are involved in
7704-418: The insulation the skin provides but can also serve as a secondary sexual characteristic or as camouflage . On some animals, the skin is very hard and thick and can be processed to create leather . Reptiles and most fish have hard protective scales on their skin for protection, and birds have hard feathers , all made of tough beta-keratins . Amphibian skin is not a strong barrier, especially regarding
7811-458: The intact skin is under compression. Small circular holes punched on the skin may widen or close into ellipses, or shrink and remain circular, depending on preexisting stresses. Tissue homeostasis generally declines with age, in part because stem /progenitor cells fail to self-renew or differentiate . Skin aging is caused in part by TGF-β by blocking the conversion of dermal fibroblasts into fat cells which provide support. Common changes in
7918-419: The intercalary system which can be summed up as a transitional region connecting the duct to the grand alveolar beneath the epidermal skin layer. In general, granular glands are larger in size than the mucous glands, which are greater in number. Granular glands can be identified as venomous and often differ in the type of toxin as well as the concentrations of secretions across various orders and species within
8025-408: The laboratory, cells can change shape or may lose specific properties such as protein expression—which processes are also termed dedifferentiation. Some hypothesize that dedifferentiation is an aberration that likely results in cancers , but others explain it as a natural part of the immune response that was lost to humans at some point of evolution. A newly discovered molecule dubbed reversine ,
8132-471: The lens vesicle of surface fish can induce other parts of the eye to develop in cave- and surface-dwelling fish, while the lens vesicle of the cave-dwelling fish cannot. Other important mechanisms fall under the category of asymmetric cell divisions , divisions that give rise to daughter cells with distinct developmental fates. Asymmetric cell divisions can occur because of asymmetrically expressed maternal cytoplasmic determinants or because of signaling. In
8239-410: The likely existence of further such mechanisms. In order to fulfill the purpose of regenerating a variety of tissues, adult stems are known to migrate from their niches, adhere to new extracellular matrices (ECM) and differentiate. The ductility of these microenvironments are unique to different tissue types. The ECM surrounding brain, muscle and bone tissues range from soft to stiff. The transduction of
8346-687: The major cells , constituting 95% of the epidermis , while Merkel cells , melanocytes and Langerhans cells are also present. The epidermis can be further subdivided into the following strata or layers (beginning with the outermost layer): Keratinocytes in the stratum basale proliferate through mitosis and the daughter cells move up the strata changing shape and composition as they undergo multiple stages of cell differentiation to eventually become anucleated. During that process, keratinocytes will become highly organized, forming cellular junctions ( desmosomes ) between each other and secreting keratin proteins and lipids which contribute to
8453-429: The mechanisms of reprogramming (and by extension, differentiation) are very complex and cannot be easily duplicated, as seen by the significant number of differentially methylated regions between ES and iPS cell lines. Now that these two points have been established, we can examine some of the epigenetic mechanisms that are thought to regulate cellular differentiation. Three transcription factors, OCT4, SOX2, and NANOG –
8560-434: The mesoderm instructs the epidermis of what structure to make through a series of reciprocal inductions. Transplantation experiments involving frog and newt epidermis indicated that the mesodermal signals are conserved between species but the epidermal response is species-specific meaning that the mesoderm instructs the epidermis of its position and the epidermis uses this information to make a specific structure. Skin performs
8667-412: The mucous gland appear as cylindrical vertical tubes that break through the epidermal layer to the surface of the skin. The cells lining the inside of the ducts are oriented with their longitudinal axis forming 90-degree angles surrounding the duct in a helical fashion. Intercalary cells react identically to those of granular glands but on a smaller scale. Among the amphibians, there are taxa which contain
8774-498: The oldest known skin, fossilized about 289 million years ago, and possibly the skin from an ancient reptile. The word skin originally only referred to dressed and tanned animal hide and the usual word for human skin was hide. Skin is a borrowing from Old Norse skinn "animal hide, fur", ultimately from the Proto-Indo-European root *sek-, meaning "to cut" (probably a reference to the fact that in those times animal hide
8881-410: The passage of chemicals via skin, and is often subject to osmosis and diffusive forces. For example, a frog sitting in an anesthetic solution would be sedated quickly as the chemical diffuses through its skin. Amphibian skin plays key roles in everyday survival and their ability to exploit a wide range of habitats and ecological conditions. On 11 January 2024, biologists reported the discovery of
8988-448: The placental tissue, is known as totipotent . In mammals, only the zygote and subsequent blastomeres are totipotent, while in plants, many differentiated cells can become totipotent with simple laboratory techniques. A cell that can differentiate into all cell types of the adult organism is known as pluripotent . Such cells are called meristematic cells in higher plants and embryonic stem cells in animals, though some groups report
9095-431: The presence of adult pluripotent cells. Virally induced expression of four transcription factors Oct4 , Sox2 , c-Myc , and Klf4 ( Yamanaka factors ) is sufficient to create pluripotent (iPS) cells from adult fibroblasts . A multipotent cell is one that can differentiate into multiple different, but closely related cell types. Oligopotent cells are more restricted than multipotent, but can still differentiate into
9202-617: The production of BMI1 , a component of the PcG complex that recognizes H3K27me3 . This occurs in a Gli-dependent manner, as Gli1 and Gli2 are downstream effectors of the Hedgehog signaling pathway . In culture, Bmi1 mediates the Hedgehog pathway's ability to promote human mammary stem cell self-renewal. In both humans and mice, researchers showed Bmi1 to be highly expressed in proliferating immature cerebellar granule cell precursors. When Bmi1
9309-514: The progenitor and embryonic cell lines. In vitro -induced differentiation of iPSC lines saw transmission of 88% and 46% of hyper and hypo-methylated differentially methylated regions, respectively. Two conclusions are readily apparent from this study. First, epigenetic processes are heavily involved in cell fate determination , as seen from the similar levels of cytosine methylation between induced pluripotent and embryonic stem cells, consistent with their respective patterns of transcription . Second,
9416-653: The realm of gene silencing , Polycomb repressive complex 2 , one of two classes of the Polycomb group (PcG) family of proteins, catalyzes the di- and tri-methylation of histone H3 lysine 27 (H3K27me2/me3). By binding to the H3K27me2/3-tagged nucleosome, PRC1 (also a complex of PcG family proteins) catalyzes the mono-ubiquitinylation of histone H2A at lysine 119 (H2AK119Ub1), blocking RNA polymerase II activity and resulting in transcriptional suppression. PcG knockout ES cells do not differentiate efficiently into
9523-419: The relative size of their chromatophores . Amphibians possess two types of glands , mucous and granular (serous). Both of these glands are part of the integument and thus considered cutaneous . Mucous and granular glands are both divided into three different sections which all connect to structure the gland as a whole. The three individual parts of the gland are the duct, the intercalary region, and lastly
9630-581: The reticular region are the roots of the hair , sweat glands , sebaceous glands , receptors , nails , and blood vessels . The subcutaneous tissue (also hypodermis) is not part of the skin, and lies below the dermis . Its purpose is to attach the skin to underlying bone and muscle as well as supplying it with blood vessels and nerves . It consists of loose connective tissue and elastin . The main cell types are fibroblasts , macrophages and adipocytes (the subcutaneous tissue contains 50% of body fat ). Fat serves as padding and insulation for
9737-416: The role of cell signaling in influencing the epigenetic processes governing differentiation. Such a role should exist, as it would be reasonable to think that extrinsic signaling can lead to epigenetic remodeling, just as it can lead to changes in gene expression through the activation or repression of different transcription factors. Little direct data is available concerning the specific signals that influence
9844-419: The same genome . A specialized type of differentiation, known as terminal differentiation , is of importance in some tissues, including vertebrate nervous system , striated muscle , epidermis and gut. During terminal differentiation, a precursor cell formerly capable of cell division permanently leaves the cell cycle, dismantles the cell cycle machinery and often expresses a range of genes characteristic of
9951-419: The same genome, determination of cell type must occur at the level of gene expression. While the regulation of gene expression can occur through cis- and trans-regulatory elements including a gene's promoter and enhancers , the problem arises as to how this expression pattern is maintained over numerous generations of cell division . As it turns out, epigenetic processes play a crucial role in regulating
10058-511: The same was true of only 60% of CG dinucleotides in somatic cells. In addition, somatic cells possessed minimal levels of cytosine methylation in non-CG dinucleotides, while induced pluripotent cells possessed similar levels of methylation as embryonic stem cells, between 0.5 and 1.5%. Thus, consistent with their respective transcriptional activities, DNA methylation patterns, at least on the genomic level, are similar between ESCs and iPSCs. However, upon examining methylation patterns more closely,
10165-465: The skin and the nervous system, the mesoderm forms the bones and muscular tissue, and the endoderm forms the internal organ tissues. Dedifferentiation , or integration, is a cellular process seen in the more basal life forms in animals, such as worms and amphibians where a differentiated cell reverts to an earlier developmental stage—usually as part of a regenerative process. Dedifferentiation also occurs in plant cells. And, in cell culture in
10272-656: The skin as a result of aging range from wrinkles , discoloration, and skin laxity, but can manifest in more severe forms such as skin malignancies. Moreover, these factors may be worsened by sun exposure in a process known as photoaging . Cuticle A cuticle ( / ˈ k juː t ɪ k əl / ), or cuticula , is any of a variety of tough but flexible, non-mineral outer coverings of an organism, or parts of an organism, that provide protection. Various types of "cuticle" are non- homologous , differing in their origin, structure, function, and chemical composition. In human anatomy , "cuticle" can refer to several structures, but it
10379-418: The skin located under the eyes and around the eyelids is the thinnest skin on the body at 0.5 mm thick and is one of the first areas to show signs of aging such as "crows feet" and wrinkles. The skin on the palms and the soles of the feet is the thickest skin on the body at 4 mm thick. The speed and quality of wound healing in skin is promoted by estrogen . Fur is dense hair. Primarily, fur augments
10486-419: The stem cells into these cells types is not directed solely by chemokine cues and cell to cell signaling. The elasticity of the microenvironment can also affect the differentiation of mesenchymal stem cells (MSCs which originate in bone marrow.) When MSCs are placed on substrates of the same stiffness as brain, muscle and bone ECM, the MSCs take on properties of those respective cell types. Matrix sensing requires
10593-442: The surface tension of the liquid to permit any flow into the space between the plateaus, then the area of contact between liquid and solid surfaces may be reduced to a small fraction of what a smooth surface might permit. The effect is to reduce wetting of the surface substantially. Structural coloration is also observed in the cuticles of plants (see, as an example, the so-called "marble berry", Pollia condensata . "Cuticle"
10700-478: The target cell. Cells and tissues can vary in competence, their ability to respond to external signals. Signal induction refers to cascades of signaling events, during which a cell or tissue signals to another cell or tissue to influence its developmental fate. Yamamoto and Jeffery investigated the role of the lens in eye formation in cave- and surface-dwelling fish, a striking example of induction. Through reciprocal transplants, Yamamoto and Jeffery found that
10807-532: The three germ layers, and deletion of the PRC1 and PRC2 genes leads to increased expression of lineage-affiliated genes and unscheduled differentiation. Presumably, PcG complexes are responsible for transcriptionally repressing differentiation and development-promoting genes. Alternately, upon receiving differentiation signals, PcG proteins are recruited to promoters of pluripotency transcription factors. PcG-deficient ES cells can begin differentiation but cannot maintain
10914-490: The toxic effects of salt . Some plants, particularly those adapted to life in damp or aquatic environments, have an extreme resistance to wetting. A well-known example is the sacred lotus . This adaptation is not purely the physical and chemical effect of a waxy coating but depends largely on the microscopic shape of the surface. When a hydrophobic surface is sculpted into microscopic , regular, elevated areas, sometimes in fractal patterns, too high and too closely spaced for
11021-419: The transcription of target genes. While highly expressed, their levels require a precise balance to maintain pluripotency, perturbation of which will promote differentiation towards different lineages based on how the gene expression levels change. Differential regulation of Oct-4 and SOX2 levels have been shown to precede germ layer fate selection. Increased levels of Oct4 and decreased levels of Sox2 promote
11128-418: The two layers of skin. The reticular region lies deep in the papillary region and is usually much thicker. It is composed of dense irregular connective tissue and receives its name from the dense concentration of collagenous , elastic , and reticular fibers that weave throughout it. These protein fibers give the dermis its properties of strength , extensibility , and elasticity . Also located within
11235-451: The unique polymers cutin or cutan , impregnated with wax . Plant cuticles function as permeability barriers for water and water-soluble materials. They prevent plant surfaces from becoming wet and also help to prevent plants from drying out. Xerophytic plants such as cacti have very thick cuticles to help them survive in their arid climates. Plants that live in range of sea's spray also may have thicker cuticles that protect them from
11342-451: Was commonly cut off to be used as garment). Mammalian skin is composed of two primary layers: The epidermis is composed of the outermost layers of the skin. It forms a protective barrier over the body's surface, responsible for keeping water in the body and preventing pathogens from entering, and is a stratified squamous epithelium , composed of proliferating basal and differentiated suprabasal keratinocytes . Keratinocytes are
11449-478: Was knocked out in mice, impaired cerebellar development resulted, leading to significant reductions in postnatal brain mass along with abnormalities in motor control and behavior. A separate study showed a significant decrease in neural stem cell proliferation along with increased astrocyte proliferation in Bmi null mice. An alternative model of cellular differentiation during embryogenesis is that positional information
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