Direct Reprogramming Facilitated by Small Molecules

Abstract

The ability to reprogram cellular fate provide great hope for regenerative medicine and offer excellent cellular resources for disease modeling and drug discovery. Direct reprogramming, also called lineage reprogramming or transdifferentiation, is the process of changing one cell type to another without going through an intermediate pluripotent step. Direct reprogramming is generally achieved using lineage-specific transcription factors or microRNAs. The efficiency of direct reprogramming is usually relatively low without the aid of small molecule compounds. By using small molecules in conjunction with transcription factors or microRNAs, the efficiency of direct reprogramming is greatly increased and sometimes even less transgenes are required. Common targets of the small molecules used in direct reprogramming include epigenetic regulators, such as DNA methyltransferases and histone deacetylases, and signaling molecules, such as GSK3β and TGFβ pathways. By modulating epigenetic landscape and signaling pathways critical for cell fate determination, these small molecules allow cell fate conversion in a rapid and efficient manner. This review aims to highlight the versatile roles of small molecules in direct reprogramming.