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Germ line cells are any line of cells that give rise to gametes —eggs and sperm—and thus are continuous through 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.

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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 a hollow sphere of cells, called a blastocyst. 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: [ citation needed ]. A pathway that 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 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 often seen in more basal life forms such as worms and amphibians in which a partially or terminally differentiated cell reverts to an earlier developmental stage, usually as part of a regenerative process. This process is also termed dedifferentiation. Some believe dedifferentiation is an aberration of the normal development cycle that results in cancer , [17] whereas others believe it to be a natural part of the immune response lost by humans at some point as a result of evolution.

A small molecule dubbed reversine , a purine analog, has been discovered that has proven to induce dedifferentiation in myotubes. These dedifferentiated 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 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. However, an alternative view has been proposed recently [ when? 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. 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.

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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.


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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.

Cellular differentiation - Wikipedia

A cascade of phosphorylation reactions eventually activates a dormant transcription factor or cytoskeletal protein, thus contributing to the differentiation process in the target cell. 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. 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.

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 the genus Volvox , a model system for studying how unicellular organisms can evolve into multicellular organisms.

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 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 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 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 paper by Lister R, et al. 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, the authors conducted whole-genome profiling of DNA methylation patterns in several human embryonic stem cell ESC , iPSC, and progenitor cell lines.

Lister R, et al. 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. However, upon examining methylation patterns more closely, the authors discovered regions of differential CG dinucleotide methylation between at least one ES or iPS cell line.

White blood cell differential

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, the mechanisms of de-differentiation 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 — 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.

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.

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. 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 the differentiated phenotype. 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.

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