Mapping the route from naive pluripotency to lineage specification - PubMed (nih.gov)

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摘要

In the mouse blastocyst, epiblast cells are newly formed shortly before implantation. They possess a unique developmental plasticity, termed naive pluripotency. For development to proceed, this naive state must be subsumed by multi-lineage differentiation within 72 h following implantation. In vitro differentiation of naive embryonic stem cells (ESCs) cultured in controlled conditions provides a tractable system to dissect and understand the process of exit from naive pluripotency and entry into lineage specification. Exploitation of this system in recent large-scale RNAi and mutagenesis screens has uncovered multiple new factors and modules that drive or facilitate progression out of the naive state. Notably, these studies show that the transcription factor network that governs the naive state is rapidly dismantled prior to upregulation of lineage specification markers, creating an intermediate state that we term formative pluripotency. Here, we summarize these findings and propose a road map for state transitions in ESC differentiation that reflects the orderly dynamics of epiblast progression in the embry
在小鼠囊胚中，上胚层细胞在植入前不久新形成。它们具有独特的发育可塑性，称为初始态（naive）多能性。为了继续发育，这种naive状态必须在植入后 72 小时内被多谱系分化所代替。在受控条件下培养的naive胚胎干细胞 (ESC) 的体外分化提供了一个易于处理的系统来剖析和了解从naive多能性退出和进入谱系分化的过程。在最近的大规模 RNAi 和诱变筛选中对该系统的开发发现了多个新的因素和模块，这些因素和模块驱动或促进了从naive状态撤出的进展。值得注意的是，这些研究表明，控制naive状态的转录因子网络在谱系分化标记物上调之前迅速瓦解，产生了我们称之为活化态/定形态/可塑态（formative）多能性的中间状态。在这里，我们总结了这些发现，并提出了 ESC 分化状态转换的路线图，该路线图反映了胚胎中上胚层发育的有序动态。

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笔记