Perspectives on somatic reprogramming: spotlighting epigenetic regulation and cellular heterogeneity

Induction of pluripotency in somatic cells via ectopic expression of defined factors demonstrates the reversibility of developmental programming, thus serves as an ideal model to investigate the underlying principles of cell fate determination, which drives the differentiation of various cell types from an identical genome. Over the last decade, our understanding has grown considerably regarding how somatic reprogramming initiates and be regulated. Recent mechanistic investigations on chromatin architecture regulation and cell heterogeneity significantly contribute to the understanding of somatic reprogramming. Specifically, it is found that chromatin dynamics which are regulated by the orchestration of transcriptional factors and epigenetic regulation, play an important role during somatic reprogramming. Moreover, the widespread application of single-cell technologies reveals latent cell fate transition trajectories during the reprogramming process. Here, we highlighted several mechanistic studies on somatic reprogramming, particularly from epigenetic regulation and cell heterogeneity perspectives, and summarized their contribution to our current understanding of cell fate determination.