Chemicals as the Sole Transformers of Cell Fate

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.