A central question of biology is the basis of stable cell fates. Cell fates are formed during development, where the zygote progresses from totipotency to terminal differentiation. Each step of lineage commitment involves establishment of stable states encoding-specific developmental commitments that can be faithfully transmitted to daughter cells — a ‘memory’ of cell fate is acquired. However, this cell-fate memory is reversible and can be changed when experimental reprogramming procedures such as nuclear transfer to eggs or transcription factor overexpression are used. The ability to reprogram cell fates impacts regenerative medicine, as progress in understanding underlying molecular mechanisms of cell-fate changes can allow the generation of any cell type needed for cell replacement therapies. Given its potential, studies are currently aiming at improving the low efficiency of cell-fate conversion. In recent years, epigenetic mechanisms suggested to promote stable cell-fate memory emerged as factors that cause resistance to cell-fate conversions during nuclear reprogramming. In this review, we highlight the latest work that has characterised epigenetic barriers to reprogramming which, during normal development, help to maintain the stable differentiation status of cells.

生物学的一个核心问题是稳定细胞命运的基础。细胞命运是在发育过程中形成的，受精卵从全能性发展到终末分化。谱系承诺的每一步都涉及建立稳定状态，编码特定的发育承诺，可以忠实地传递给子细胞——获得细胞命运的“记忆”。然而，这种细胞命运记忆是可逆的，并且可以在使用诸如核移植到卵子或转录因子过度表达等实验性重编程程序时改变。重新编程细胞命运的能力会影响再生医学，因为在了解细胞命运变化的潜在分子机制方面取得的进展可以允许产生细胞替代疗法所需的任何细胞类型。鉴于其潜力，目前的研究旨在改善细胞命运转换的低效率。近年来，表观遗传机制表明促进稳定的细胞命运记忆成为导致核重编程过程中对细胞命运转换产生抵抗的因素。在这篇综述中，我们重点介绍了表征重编程的表观遗传障碍的最新工作，这些障碍在正常发育过程中有助于维持细胞的稳定分化状态。