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Cell type BasicReference: Buddy Ratner, Biomaterial Science, Pg 255

Basic functional attributes of cells include nutrient absorption andassimilation, respiration, synthesis of macromolecules, growth, and

reproduction. Without these basic activities, cells cannot live.However, most cells also exhibit specialization, that is, they haveadditional capabilities, such as irritability, conductivity, absorption, orsecretion of molecules (for use by other cells).Multicellular organisms are thus composed of individual cells withmarked specialization of structure and function. These differentiatedcells allow a division of labor in the performance and coordination ofcomplex functions carried out in architecturally distinct and organizedtissues. The structural and functional changes that occur duringcellular differentiation are usually irreversible.A cell type is a distinct morphological or functional form of cell. When a

cell switches state from one cell type to another, it undergoes cellulardifferentiation. A list of distinct cell types in the adult human body mayinclude several hundred distinct types.

Cell typesReference:WikipediaThree basic categories of cells make up the mammalian body: germcells, somatic cells, and stem cells. Each of the approximately 100trillion (1014) cells in an adult human has its own copy or copies of thegenome (except certain cell types, such as red blood cells, that lacknuclei).

Somatic cells are diploid having two copies of each chromosome. Cellsdifferentiate to specialize for different functions. They make up most ofthe human body, such as skin and muscle cells.Germ line cells are any line of cells that give rise to gameteseggsand spermand thus are continuous through the generations. Germcells are haploid, having one set of all chromosome.Stem cells have the ability to divide for indefinite periods and also togive rise to specialized cells. Pluripotent stem cells undergo furtherspecialization into multipotent progenitor cells that then give rise tofunctional cells. Properties that differentiate a stem cell from othercells: a) Self-renewal - the ability to go through numerous cycles of cell

division while maintaining the undifferentiated state. B) Potency - thecapacity to differentiate into specialized cell types. Stem cells can beeither totipotent or pluripotent - to be able to give rise to any maturecell type. Multipotent or unipotent progenitor cells are also present.Examples of stem and progenitor cells include:

Hematopoietic stem cells (adult stem cells) from the bonemarrow that give rise to red blood cells, white blood cells, andplatelets

http://en.wikipedia.org/wiki/Gameteshttp://en.wikipedia.org/wiki/Gametes

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Mesenchymal stem cells (adult stem cells) from the bone marrowthat give rise to stromal cells, fat cells, and types of bone cells

Epithelial stem cells (progenitor cells) that give rise to thevarious types of skin cells

Muscle satellite cells (progenitor cells) that contribute to

differentiated muscle tissue

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Different types of potency in stem cellsPotency of stem cell specifies the potential to differentiate into

different cell types Totipotent stem cells can differentiate into embryonic and extra-embryonic cell types. Can construct a complete, viable organism;Produced from the fusion of an egg and sperm cell; Cells from first fewdivisions of the fertilized egg are also totipotent.Pluripotent stem cells can differentiate into nearly all cells. Egs., cellsderived from any of the three germ layers.Multipotent stem cells can differentiate into a number of cells, but only

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To ensure self-renewal, the stem cellhas to undergo 2 types of divisionsSymmetric division gives rise to twoidentical daughter cells both endowedwith stem cell propertiesAsymmetric division produces only onestem cell and a progenitor cell withlimited self-renewal potentialProgenitors can go through severalrounds of cell division before terminallydifferentiating into a mature cell

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potential, metabolic activity, and responsiveness to signals. Thesechanges are largely due to highly controlled modifications in geneexpression. With a few exceptions, cellular differentiation almost neverinvolves a change in the DNA sequence itself. Thus, different cells canhave very different physical characteristics despite having the same

genome.Cellular differentiation involves an alteration in gene expression.Every cell in the body has the same complement of genes (called thegenotype). With progressive differentiation, selected subsets of genesare preferentially expressed, yielding a distinct biological profile (calledthe phenotype). As cells progressively specialize, more and more of theunnecessary genes in the differentiating cell are irreversibly turnedoff. Some genes are active at all times (constitutively expressed);others may be selectively activated or modulated depending onexternal influences (e.g., injury).

Cell Differentiation mechanismEach specialized cell type in an organism expresses a subset of all thegenes that constitute the genome of that species. Each cell type isdefined by its particular pattern of regulated gene expression. Celldifferentiation is thus a transition of a cell from one cell type to anotherand it involves a switch from one pattern of gene expression toanother. Cellular differentiation during development can be understoodas the result of a gene regulatory network. A regulatory gene and itscis-regulatory modules are nodes in a gene regulatory network; theyreceive input and create output elsewhere in the network.

A few evolutionarily conserved types of molecular processes are

often involved in the cellular mechanisms that control these switches. The major types of molecular processes that control cellulardifferentiation involve cell signaling. Many of the signal molecules thatconvey information from cell to cell during the control of cellulardifferentiation are called growth factors.

Although the details of specific signal transduction pathwaysvary, these pathways often share the following general steps. A ligandproduced by one cell binds to a receptor in the extracellular region ofanother cell, inducing a conformational change in the receptor. Theshape of the cytoplasmic domain of the receptor changes, and thereceptor acquires enzymatic activity. The receptor then catalyzes

reactions that phosphorylate other proteins, activating them. Acascade of phosphorylation reactions eventually activates a dormanttranscription factor or cytoskeletal protein, thus contributing to thedifferentiation process in the target cell. Cells and tissues can vary incompetence, their ability to respond to external signals.

Epigenetic influence on differentiationSince each cell, regardless of cell type, possesses the same

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genome, determination of cell type must occur at the level of geneexpression. While the regulation of gene expression can occur throughcis- and trans-regulatory elements including a genes promoter andenhancers, the problem arises to how this expression pattern ismaintained over numerous generations of cell division. As it turns out,

epigenetic processes play a crucial role in regulating the decision toadopt a stem, progenitor, or mature cell fate.Three transcription factors, OCT4, SOX2, and NANOG, are highlyexpressed in undifferentiated embryonic stem cells and are necessaryfor the maintenance of their pluripotency. It is thought that theyachieve this through alterations in chromatin structure, such as histonemodification and DNA methylation, to restrict or permit thetranscription of target genes. Upon receiving differentiation signals,PcG proteins are recruited to promoters of pluripotency transcriptionfactors. PcG-deficient ES cells can begin differentiation but are unableto maintain the differentiated phenotype

Signalling molecules in Differentiationseveral major candidates thought to be involved in the induction andmaintenance of both embryonic stem cells and their differentiatedprogenyWnt signaling pathway. The Wnt pathway is involved in all stages ofdifferentiation, and the ligand Wnt3a can substitute for theoverexpression of c-Myc in the generation of induced pluripotent stemcells. On the other hand, disruption of -catenin, a component of theWnt signaling pathway, leads to decreased proliferation of neuralprogenitors.

Growth factors comprise the second major set of candidates ofepigenetic regulators of cellular differentiation. These morphogens arecrucial 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 ofOCT4, SOX2, and NANOG by downstream signaling to Smad proteins.Depletion of growth factors promotes the differentiation of ESCsCytokine leukemia inhibitory factors are associated with themaintenance of mouse ESCs in an undifferentiated state. This isachieved through its activation of the Jak-STAT3 pathway, which hasbeen shown to be necessary and sufficient towards maintaining mouse

ESC pluripotency. Retinoic acid can induce differentiation of humanand mouse ESCs and Notch signaling is involved in the proliferationand self-renewal of stem cells. Finally, Sonic hedgehog, in addition toits role as a morphogen, promotes embryonic stem cell differentiationand the self-renewal of somatic stem cells

Cell Dedifferentiation

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Nevertheless, recent evidence suggests that cells of end-stage,specialized and highly differentiated tissues can, under certainconditions such as following injury, dedifferentiate into multi- potentforms or serve as stem cells capable of generating more specializedcells

Cells derived from endoderm:Gland cells (exocrine&endocrine)Epithelial cells lining internal cavitiesCells derived from endoderm:Integumentary systemNervous systemCells derived from mesodermMetabolism & storage cells (adipocytes, liocytes, hepatocytes)Barrier function cells (lungs, gut, exocrine glands, urogenital tract)

Extracellular matrix cells