Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom.
Curr Opin Genet Dev. 2012 Oct;22(5):466-74. doi: 10.1016/j.gde.2012.06.002. Epub 2012 Jul 12.
Development of mammalian primordial germ cells (PGCs) presents a unique example of a cell fate specification event that is intimately linked with epigenetic reprogramming. Cell fate commitment is governed by transcription factors which, together with epigenetic regulators, instruct lineage choice in response to signalling cues. Similarly, the reversal of epigenetic silencing is driven by the combinatorial action of transcriptional regulators, resulting in an increase in cellular plasticity. PGCs constitute a paradox, since their development as a unipotent specialised lineage is coupled with extensive reprogramming, which eventually leads to an increase in cellular potency. In this review we discuss the role of key factors in the specification of the germ cell lineage that are also important for the comprehensive erasure of epigenetic modifications, which provides the foundation for regeneration of totipotency. We further discuss current concepts of transcriptional and epigenetic control of cell fate decisions, with a particular focus on emerging principles of enhancer activity and their potential implications for the transcriptional control of PGC specification.
哺乳动物原始生殖细胞 (PGC) 的发育呈现了一个独特的细胞命运特化事件的范例，该事件与表观遗传重编程密切相关。细胞命运的决定受转录因子控制，这些转录因子与表观遗传调控因子一起，根据信号线索指示谱系选择。同样，表观遗传沉默的逆转是由转录调控因子的组合作用驱动的，导致细胞可塑性增加。PGC 构成了一个悖论，因为它们作为单一能特化谱系的发育伴随着广泛的重编程，最终导致细胞潜能的增加。在这篇综述中，我们讨论了在生殖细胞谱系特化中起关键作用的因素，这些因素对于全面消除表观遗传修饰也很重要，这为全能性的再生提供了基础。我们进一步讨论了细胞命运决定的转录和表观遗传控制的当前概念，特别关注增强子活性的新兴原则及其对 PGC 特化的转录控制的潜在影响。
