International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto 860-0811, Japan.
Center for Biosystems Dynamics Research (BDR), RIKEN, Kobe 650-0047, Japan.
Development. 2020 Feb 3;147(3):dev184960. doi: 10.1242/dev.184960.
The pluripotent epiblast gives rise to all tissues and organs in the adult body. Its differentiation starts at gastrulation, when the epiblast generates mesoderm and endoderm germ layers through epithelial-mesenchymal transition (EMT). Although gastrulation EMT coincides with loss of epiblast pluripotency, pluripotent cells in development and can adopt either mesenchymal or epithelial morphology. The relationship between epiblast cellular morphology and its pluripotency is not well understood. Here, using chicken epiblast and mammalian pluripotency stem cell (PSC) models, we show that PSCs undergo a mesenchymal-epithelial transition (MET) prior to EMT-associated pluripotency loss. Epiblast MET and its subsequent EMT are two distinct processes. The former, a partial MET, is associated with reversible initiation of pluripotency exit, whereas the latter, a full EMT, is associated with complete and irreversible pluripotency loss. We provide evidence that integrin-mediated cell-matrix interaction is a key player in pluripotency exit regulation. We propose that epiblast partial MET is an evolutionarily conserved process among all amniotic vertebrates and that epiblast pluripotency is restricted to an intermediate cellular state residing between the fully mesenchymal and fully epithelial states.
多能的上胚层产生成体身体中的所有组织和器官。它的分化始于原肠胚形成，当时上胚层通过上皮-间充质转化（EMT）产生中胚层和内胚层胚层。尽管原肠胚形成 EMT 与上胚层多能性丧失同时发生，但发育中的多能细胞可以采用间质或上皮形态。上胚层细胞形态与其多能性之间的关系尚不清楚。在这里，我们使用鸡上胚层和哺乳动物多能性干细胞（PSC）模型，表明 PSC 在 EMT 相关多能性丧失之前经历了间质-上皮转化（MET）。上胚层 MET 及其随后的 EMT 是两个不同的过程。前者是部分 MET，与多能性退出的可逆启动有关，而后者是完全 EMT，与完全和不可逆的多能性丧失有关。我们提供的证据表明整合素介导的细胞-基质相互作用是多能性退出调节的关键因素。我们提出，上胚层部分 MET 是所有羊膜脊椎动物中保守的过程，而上胚层多能性仅限于位于完全间质和完全上皮状态之间的中间细胞状态。
