Reprogramming

Reprogramming refers to the regression of a specialized cell to a simpler state, resulting in cells with stem-like properties, or the direct reprogramming of one specialized cell type into another. The process of cells regressing to a stem-like state occurs naturally, mostly for repair and regeneration in aged or damaged tissues.

Products
Background
Literature
Cat No Product Name / Activity
6044 AS 8351
Induces reprogramming of fibroblasts into functional cardiomyocytes
4055 L-Ascorbic acid
Enhances the generation of iPSCs; increases reprogramming efficiency
3842 5-Azacytidine
DNA methyltransferase inhibitor. Improves reprogramming efficiency
1544 (±)-Bay K 8644
Ca2+ channel activator (L-type); aids generation of iPSCs from MEFs
5819 Bexarotene
Potent and selective RXR agonist; induces brown adipogenic reprogramming from myoblasts
3364 BIX 01294
GLP and G9a inhibitor; potentiates induction of iPSCs
4423 CHIR 99021
Highly selective GSK-3 inhibitor; enables reprogramming of mouse embryonic fibroblasts into iPS cells
4489 DBZ
Notch signaling pathway inhibitor; stimulates formation of iPSCs
4703 3-Deazaneplanocin A hydrochloride
Histone methyltransferase inhibitor; enhances Oct4 expression in chemically-induced pluripotent stem cells
1425 (S)-(+)-Dimethindene maleate
Allows formation of extended pluripotent stem (EPS) cells; also M2-selective antagonist
1398 Kenpaullone
Promotes generation of iPSCs from somatic cells; also potent cdk inhibitor and GSK-3 inhibitor
3268 Minocycline hydrochloride
Allows formation of extended pluripotent stem (EPS) cells; also antibiotic
3656 Neurodazine
Induces neurogenesis in mature skeletal muscle cells
5639 O4I1
Oct3/4 inducer
5664 O4I2
Oct3/4 inducer; induces expression of pluripotent-associated genes
6066 OAC-2
Oct4 activator; enhances iPSC reprogramming efficiency
4887 OAC-1
Oct4 activator; enhances iPSC reprogramming efficiency
4192 PD 0325901
Selective inhibitor of MEK1/2; enhances generation of iPSCs
2653 Pifithrin-μ
Inhibitor of p53-mitochondrial binding
3742 RepSox
Selective TGF-βRI inhibitor; enhances reprogramming efficiency
3295 RG 108
Non-nucleoside DNA methyltransferase inhibitor; enhances efficiency of iPSC generation
4297 SMER 28
Promotes reprogramming of fibroblasts to neural stem-like cells
3845 Thiazovivin
Improves the efficiency of fibroblast reprogramming and induction of iPSCs
3852 Tranylcypromine hydrochloride
Irreversible inhibitor of LSD1; enables reprogramming of mouse embryonic fibroblasts into iPS cells
1406 Trichostatin A
Potent histone deacetylase inhibitor; induces accelerated dedifferentiation of primordial germ cells
0761 TTNPB
Retinoic acid analog; enhances efficiency of reprogramming in CiPSCs
2815 Valproic acid, sodium salt
Histone deacetylase inhibitor; enables induction of pluripotent stem cells from somatic cells

Reprogramming refers to the regression of a specialized cell to a simpler state, resulting in cells with stem-like properties, or the direct reprogramming of one specialized cell type into another. The process of cells regressing to a stem-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 Oct3/4, 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 chemical reagents in the generation of iPSCs. 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.

iPSCs are valuable in biomedical research as they are pluripotent and can therefore theoretically be turned 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, or in organ transplantation to generate human organ tissues. 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 embryonic stem cells.

Functionally mature cells may also be reprogrammed directly into a different specialized cell type without passing through the iPSC state, a process that is known as direct lineage reprogramming. This process also occurs naturally and is known as transdifferentiation.

Literature for Reprogramming

Stem Cells

Stem Cells Scientific Review

Written by Kirsty E. Clarke, Victoria B. Christie, Andy Whiting and Stefan A. Przyborski, this review provides an overview of the use of small molecules in the control of stem cell growth and differentiation. Key signaling pathways are highlighted, and the regulation of ES cell self-renewal and somatic cell reprogramming is discussed. Compounds available from Tocris are listed.