Int J Stem Cells.  2016 May;9(1):9-20. 10.15283/ijsc.2016.9.1.9.

Chemicals as the Sole Transformers of Cell Fate

• Ebrahimi B

• KMID: 2164156
• DOI: http://doi.org/10.15283/ijsc.2016.9.1.9

Abstract

Forced expression of lineage-specific transcription factors in somatic cells can result in the generation of different cell types in a process named direct reprogramming, bypassing the pluripotent state. However, the introduction of transgenes limits the therapeutic applications of the produced cells. Numerous small-molecules have been introduced in the field of stem cell biology capable of governing self-renewal, reprogramming, transdifferentiation and regeneration. These chemical compounds are versatile tools for cell fate conversion toward desired outcomes. Cell fate conversion using small-molecules alone (chemical reprogramming) has superiority over arduous traditional genetic techniques in several aspects. For instance, rapid, transient, and reversible effects in activation and inhibition of functions of specific proteins are of the profits of small-molecules. They are cost-effective, have a long half-life, diversity on structure and function, and allow for temporal and flexible regulation of signaling pathways. Additionally, their effects could be adjusted by fine-tuning concentrations and combinations of different small-molecules. Therefore, chemicals are powerful tools in cell fate conversion and study of stem cell and chemical biology in vitro and in vivo. Moreover, transgene-free and chemical-only transdifferentiation approaches provide alternative strategies for the generation of various cell types, disease modeling, drug screening, and regenerative medicine. The current review gives an overview of the recent findings concerning transdifferentiation by only small-molecules without the use of transgenes.

Keyword

Small-molecule; Cellular reprogramming; Transdifferentiation; Regenerative medicine

MeSH Terms

Biology
Drug Design
Genetic Techniques
Half-Life
Mass Screening
Regeneration
Regenerative Medicine
Stem Cells
Transcription Factors
Transgenes
Transcription Factors

Figure

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  Fig. 1 Current progress in chemical-only transdifferentiation. A chemical cocktail induces the starting cells into an intermediate or immature state. Then, the immature cells are converted into different mature and progenitor cells (e.g. neurons, neural progenitor cells, neuroblasts, cardiomyocytes, endothelial cells, and pancreatic β-like cells) by small-molecules and growth factors in a stepwise manner. The intermediate state in the figure is indicative of the induced cells that are immature. Upper part shows stepwise chemical-only transdifferentiation of astrocytes into neuroblasts and neurons. Another paradigm is that the starting cells are directed toward a plastic state by specific chemicals and then they are differentiated into certain lineages by specific soluble signals (i.e. small-molecules and growth factors).

Reference

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