Reprogramming cell fates by small molecules

Abstract

Reprogramming cell fates towards pluripotent stem cells and other cell types has revolutionized our understanding of cellular plasticity. During the last decade, transcription factors and microRNAs have become powerful reprogramming factors for modulating cell fates. Recently, many efforts are focused on reprogramming cell fates by non-viral and non-integrating chemical approaches. Small molecules not only are useful in generating desired cell types in vitro for various applications, such as disease modeling and cell-based transplantation, but also hold great promise to be further developed as drugs to stimulate patients' endogenous cells to repair and regenerate in vivo. Here we will focus on chemical approaches for generating induced pluripotent stem cells, neurons, cardiomyocytes, hepatocytes and pancreatic β cells. Significantly, the rapid and exciting advances in cellular reprogramming by small molecules will help us to achieve the long-term goal of curing devastating diseases, injuries, cancers and aging.

Keywords: cell fates; reprogramming; small molecules; stem cells.

Figure 1

Reprogramming cell fates by small molecules. Chemical approaches can be widely applied to manipulate cell fates and states, including pluripotent reprogramming, directed differentiation, and lineage reprogramming. Small molecules not only are useful in generating functional cell types, such as cardiomyocytes, hepatocytes, pancreatic β cells, and neurons, but also can provide a better understanding of the detailed mechanisms underlying specific reprogramming processes

Figure 2

Potential applications of cellular reprogramming. Cellular reprogramming can provide a large number of functional cells, which can be used for cell-based transplantation and high-throughput chemical screenings. This technology will help develop drugs to stimulate patients’ endogenous cells to repair and regenerate in vivo in the near future. Cellular reprogramming by only small molecules will significantly advance biomedical studies and clinical applications, and realize the long-term goal of curing degenerative diseases, injuries, and aging