Stem Cell Reprogramming typically refers to the regression of a specialized cell to a simpler state, resulting in cells with stem-like properties. This process occurs naturally, mostly for repair and regeneration in aged or damaged tissues, but can also be artificially induced using transcription factors and/or chemical reagents. Specialized cells may also be reprogrammed directly into another cell type, a process termed transdifferentiation.

Potent and selective RXR agonist; induces brown adipogenic reprogramming from myoblasts Enhances Yamanaka factor reprogramming and replaces Oct-4 in transcription factor-mediated reprogramming; synthetic thymidine analog Highly potent and selective GSK-3 inhibitor; can be used in differentiation and reprogramming of stem cells Highly selective GSK-3 inhibitor; enables reprogramming of mouse embryonic fibroblasts into iPS cells Highly potent and selective ROCK 2 inhibitor; improves cell survival after cryogeneisis Enhances reprogramming to pluripotency; facilitates telomere maintenance and increases telomere length Histone methyltransferase inhibitor; enhances Oct4 expression in chemically-induced pluripotent stem cells Allows formation of extended pluripotent stem (EPS) cells; also M2-selective antagonist Induces reprogramming of fibroblasts into functional cardiomyocytes (9C cocktail); potent PDGFRα and PDGFRβ inhbitor Non-nucleoside DNA methyltransferase inhibitor; enhances efficiency of iPSC generation Replaces SOX2 in reprogramming protocols; potent and selective inhibitor of TGF-βRI, ALK4 and ALK7 Improves the efficiency of fibroblast reprogramming and induction of iPSCs; ROCK inhibitor Irreversible inhibitor of LSD1; enables reprogramming of mouse embryonic fibroblasts into iPS cells Potent histone deacetylase inhibitor; induces accelerated dedifferentiation of primordial germ cells Histone deacetylase inhibitor; enables induction of pluripotent stem cells from somatic cells

Reprogramming of cells refers to the regression of a specialized cell to a simpler state, resulting in cells with stem-like properties, or the direct transformation of one specialized cell type into another, which is also known as transdifferentiation. The process of cells regressing to a stem cell-like state occurs naturally, mostly for repair and regeneration in aged or damaged tissues, being also known as dedifferentiation. Reprogramming can be artificially induced using a combination of transcription factors and/or chemical reagents. This was first demonstrated by Takahashi and Yamanaka in 2006. They reprogrammed mouse fibroblasts into cells having embryonic stem cell-like properties by the introduction of the transcription factors Oct-4, Sox2, c-Myc and KIf4, using viral vectors; the resulting cells were designated induced pluripotent stem cells, or iPSCs.

The use of transcription factors in the reprogramming of cells, however, is not only inefficient but is also associated with a risk of introducing genetic mutations when inserting a transgene into the target cell\'s genome. Subsequent research has shown that transcription factors can be replaced with various small molecules in the generation of induced pluripotent stem cells. The use of chemicals to reprogram cells reduces the potential for introducing genetic mutations into the cells, as well as lowering the risk of tumor formation. It can also improve the efficiency of reprogramming. Cells reprogrammed using small molecules are termed chemically induced pluripotent stem cells or ciPSCs (see Stem Cell Protocols for more information).

Chemical Reprogramming of Stem Cells

Figure 1: Schematic outlining a protocol for the chemical reprogramming of mouse embryonic fibroblasts into induced pluripotent stem cells (iPSCs). V, Valproic acid; C, CHIR 99021; 6, Repsox; T, Tranylcypromine; F, Forskolin.

From Hou et al. (2013) Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science 341, 651. PMID: 23868920

iPSCs are valuable in biomedical research as they are pluripotent and can therefore theoretically be differentiated into any cell type. As such they have potential in drug screening and toxicity testing. They are also likely to be of use in regenerative medicine, to repair damaged tissue for example following trauma or in Parkinson s disease, or to generate human organ tissues for organ transplantation. The use of iPSCs in medicine has the advantage that the cells are autologous (self), limiting the risk of immune rejection and eliminating the need for using embryonic stem cells.

Transdifferentiation is the process by which functionally mature cells are reprogrammed directly into a different specialized cell type without passing through the iPSC state; this is also known as direct lineage reprogramming. Small molecules can also be used to transdifferentiate cells from one cell type to another. This process also occurs naturally.

Reference:

Takahashi and Yamanaka (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 125, 663. PMID: 16904174

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