Combinatorial control of cell fate and reprogramming in the mammalian germline
Combinatorial control of cell fate and reprogramming in the mammalian germline
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DOI：
10.1016/j.gde.2012.06.002
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发表时间：
2012-10-01
影响因子：
4
通讯作者：
Surani, M. Azim
中科院分区：
文献类型：
--
作者：
Magnusdottir, Erna;Gillich, Astrid;Surani, M. Azim
哺乳动物原始生殖细胞（PGCs）的发育是一个独特的细胞命运特化事件的例子，与表观遗传重编程密切相关。细胞命运的承诺是由转录因子，连同表观遗传调节，指示谱系选择响应信号线索。类似地，表观遗传沉默的逆转由转录调节因子的组合作用驱动，导致细胞可塑性的增加。PGCs构成了一个悖论，因为它们作为单能特化谱系的发育与广泛的重编程相结合，这最终导致细胞效力的增加。在这篇综述中，我们讨论了生殖细胞谱系特化中关键因素的作用，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原理及其对PGC规范的转录控制的潜在影响。
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.