Stem Cell Reprogramming

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.

Products
Background
Literature (4)
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
5015 5-BrdU
Enhances Yamanaka factor reprogramming and replaces Oct-4 in transcription factor-mediated reprogramming; synthetic thymidine analog
0543 C-1
Used as ROCK inhibitor; also inhibits PKG, PKA and PKC
6695 CHIR 98014
Highly potent and selective GSK-3 inhibitor; can be used in differentiation and reprogramming of stem cells
4423 CHIR 99021
Highly selective GSK-3 inhibitor; enables reprogramming of mouse embryonic fibroblasts into iPS cells
7163 Chroman 1
Highly potent and selective ROCK 2 inhibitor; improves cell survival after cryogeneisis
5331 CPI 203
Enhances reprogramming at low concentration; BET bromodomain inhibitor
6660 Crotonic Acid
Enhances reprogramming to pluripotency; facilitates telomere maintenance and increases telomere length
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
6340 Epiblastin A
Converts epiblast stem cells to ESCs and promotes ESC self-renewal; CK1 inhibitor
5567 EPZ 004777
Improves reprogramming efficiency; highly potent DOT1L inhibitor
6976 JNJ 10198409
Induces reprogramming of fibroblasts into functional cardiomyocytes (9C cocktail); potent PDGFRα and PDGFRβ inhbitor
1398 Kenpaullone
Promotes generation of iPSCs from somatic cells; inhibits GSK-3β and cdks
3268 Minocycline hydrochloride
Allows formation of extended pluripotent stem (EPS) cells; also antibiotic
3656 Neurodazine
Induces neurogenesis in mature skeletal muscle cells
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
1614 SB 431542
Replaces SOX2 in reprogramming protocols; potent and selective inhibitor of TGF-βRI, ALK4 and ALK7
4297 SMER 28
Promotes reprogramming of fibroblasts to neural stem-like cells
3845 Thiazovivin
Improves the efficiency of fibroblast reprogramming and induction of iPSCs; ROCK inhibitor
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
1254 Y-27632 dihydrochloride
Selective ROCK inhibitor; part of cocktail used to induce neurons from fibroblasts

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

Schematic showing example of stem cell reprogramming using small molecules

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

Literature for Stem Cell Reprogramming

Tocris offers the following scientific literature for Stem Cell Reprogramming to showcase our products. We invite you to request* or download your copy today!

*Please note that Tocris will only send literature to established scientific business / institute addresses.


Stem Cell

Stem Cell Research Product Guide

This product guide provides a background to the use of small molecules in stem cell research and lists over 200 products for use in:

  • Self-renewal and Maintenance
  • Differentiation
  • Reprogramming
  • Organoid Generation
  • Regenerative Medicine
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.

Stem Cell Workflow

Stem Cell Workflow Poster

Stem cells have potential as a source of cells and tissues for research and treatment of disease. This poster summarizes some key protocols demonstrating the use of small molecules across the stem cell workflow, from reprogramming, through self-renewal, storage and differentiation to verification. Advantages of using small molecules are also highlighted.

Stem Cells

Stem Cells Poster

Written by Rebecca Quelch and Stefan Przyborski from Durham University (UK), this poster describes the isolation of pluripotent stem cells, their maintenance in culture, differentiation, and the generation and potential uses of organoids.