Reprogramming: identifying the mechanisms that safeguard cell identity

Development and homeostasis rely upon concerted regulatory pathways to establish the specialized cell types needed for tissue function. Once a cell type is specified, the processes that restrict and maintain cell fate are equally important in ensuring tissue integrity. Over the past decade, several approaches to experimentally reprogram cell fate have emerged. Importantly, efforts to improve and understand these approaches have uncovered novel molecular determinants that reinforce lineage commitment and help resist cell fate changes. In this Review, we summarize recent studies that have provided insights into the various chromatin factors, post-transcriptional processes and features of genomic organization that safeguard cell identity in the context of reprogramming to pluripotency. We also highlight how these factors function in other experimental, physiological and pathological cell fate transitions, including direct lineage conversion, pluripotency-to-totipotency reversion and cancer.