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Cell type Basic Reference: Buddy Ratner, Biomaterial Science, Pg 255 Basic functional attributes of cells include nutrient

absorption and assimilation, respiration, synthesis of macromolecules, growth, and reproduction. Without these basic activities, cells cannot live. However, most cells also exhibit specialization, that is, they have additional capabilities, such as irritability, conductivity, absorption, or secretion of molecules (for use by other cells). Multicellular organisms are thus composed of individual cells with marked specialization of structure and function. These differentiated cells allow a division of labor in the performance and coordination of complex functions carried out in architecturally distinct and organized tissues. The structural and functional changes that occur during cellular 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 cellular differentiation. A list of distinct cell types in the adult human body may include several hundred distinct types. Cell types Reference:Wikipedia Three basic categories of cells make up the mammalian body: germ cells, somatic cells, and stem cells. Each of the approximately 100 trillion (1014) 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). Somatic cells are diploid having two copies of each chromosome. Cells differentiate to specialize for different functions. They make up most of the human body, such as skin and muscle cells. Germ line cells are any line of cells that give rise to gameteseggs and spermand thus are continuous through the generations. Germ cells are haploid, having one set of all chromosome. Stem cells have the ability to divide for indefinite periods and also to give rise to specialized cells. Pluripotent stem cells undergo further specialization into multipotent progenitor cells that then give rise to functional cells. Properties that differentiate a stem cell from other cells: a) Self-renewal - the ability to go through numerous cycles of cell division while maintaining the undifferentiated state. B) Potency - the capacity to differentiate into specialized cell types. Stem cells can be either totipotent or pluripotent - to be able to give rise to any mature cell type. Multipotent or unipotent progenitor cells are also present. Examples of stem and progenitor cells include: Hematopoietic stem cells (adult stem cells) from the bone marrow that give rise to red blood cells, white blood cells, and platelets

Mesenchymal stem cells (adult stem cells) from the bone marrow that give rise to stromal cells, fat cells, and types of bone cells Epithelial stem cells (progenitor cells) that give rise to the various types of skin cells Muscle satellite cells (progenitor cells) that contribute to differentiated muscle tissue

To ensure self-renewal, the stem cell has to undergo 2 types of divisions Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties Asymmetric division produces only one stem cell and a progenitor cell with limited self-renewal potential Progenitors can go through several rounds of cell division before terminally differentiating into a mature cell

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Different types of potency in stem cells Potency of stem cell specifies the potential to differentiate into different cell types Totipotent stem cells can differentiate into embryonic and extraembryonic cell types. Can construct a complete, viable organism; Produced from the fusion of an egg and sperm cell; Cells from first few divisions of the fertilized egg are also totipotent. Pluripotent stem cells can differentiate into nearly all cells. Egs., cells derived from any of the three germ layers. Multipotent stem cells can differentiate into a number of cells, but only

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those of a closely related family of cells. Oligopotent stem cells can differentiate into only a few cells, such as lymphoid or myeloid stem cells. Unipotent stem cells can produce only one cell type, but have the property of self-renewal which distinguishes them from non-stem cells (e.g. muscle stem cells). Increasing specialization results in a loss of cell potentiality, as well as a loss in the capacity for cell division. For example, the newly fertilized ovum is absolutely undifferentiated and has the capacity to divide extensively, ultimately giving rise to progeny that make up all the cells of the body(totipotential or pluripotential). As the cells differentiate into particular tissue pathways, they lose the ability to interconvert and develop into all cell types(multipotent). Cells capable of both dividing and yielding differentiated cells of one or more types are called stem cells.

Cell Differentiation Cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of tissues and cell types. Differentiation is a common process in adults as well: adult stem cells divide and create fully differentiated daughter cells during tissue repair and during normal cell turnover. Differentiation dramatically changes 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. With a few exceptions, cellular differentiation almost never involves a change in the DNA sequence itself. Thus, different cells can have 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 the genotype). With progressive differentiation, selected subsets of genes are preferentially expressed, yielding a distinct biological profile (called the phenotype). As cells progressively specialize, more and more of the unnecessary genes in the differentiating cell are irreversibly turned off. Some genes are active at all times (constitutively expressed); others may be selectively activated or modulated depending on external influences (e.g., injury). Cell Differentiation mechanism 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 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. 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 cellular differentiation involve 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 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 the target cell. Cells and tissues can vary in competence, their ability to respond to external signals. Epigenetic influence on differentiation Since each cell, regardless of cell type, possesses 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 genes promoter and enhancers, the problem arises 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 the decision to adopt a stem, progenitor, or mature cell fate. Three transcription factors, OCT4, SOX2, and NANOG, 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 the transcription of target genes. Upon receiving differentiation signals, PcG proteins are recruited to promoters of pluripotency transcription factors. PcG-deficient ES cells can begin differentiation but are unable to maintain the differentiated phenotype Signalling molecules in Differentiation several major candidates thought to be involved in the induction and maintenance of both embryonic stem cells and their differentiated progeny 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 -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 the differentiation of ESCs 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 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 Cell Dedifferentiation

Nevertheless, recent evidence suggests that cells of end-stage, specialized and highly differentiated tissues can, under certain conditions such as following injury, dedifferentiate into multi- potent forms or serve as stem cells capable of generating more specialized cells Cells derived from endoderm: Gland cells (exocrine&endocrine) Epithelial cells lining internal cavities Cells derived from endoderm: Integumentary system Nervous system Cells derived from mesoderm Metabolism & storage cells (adipocytes, liocytes, hepatocytes) Barrier function cells (lungs, gut, exocrine glands, urogenital tract) Extracellular matrix cells