Mesenchymal-epithelial transition regulates initiation of pluripotency exit before gastrulation
Mesenchymal-epithelial transition regulates initiation of pluripotency exit before gastrulation
复制标题
DOI：
10.1242/dev.184960
复制
发表时间：
2020-02-01
期刊：
影响因子：
4.6
通讯作者：
Sheng, Guojun
中科院分区：
文献类型：
--
作者：
Hamidi, Sofiane;Nakaya, Yukiko;Sheng, Guojun
多能外胚层发育成成人体内的所有组织和器官。其分化始于原肠胚形成，外胚层通过上皮-间充质转化（epithelial-mesenchymal transition， EMT）产生中胚层和内胚层。虽然原肠胚形成EMT与外胚层多能性的丧失同时发生，但多能性细胞在发育和体外可以采用间充质或上皮形态。外胚层细胞形态与其多能性之间的关系尚不清楚。在这里，我们使用鸡外胚层和哺乳动物多能干细胞（PSC）模型，发现PSC在emt相关的多能性丧失之前经历了间充质-上皮转化（MET）。上皮细胞MET和随后的EMT是两个不同的过程。前者，部分EMT，与多能性退出的可逆启动有关，而后者，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控的关键参与者。我们认为，在所有羊膜脊椎动物中，外胚层部分MET是一个进化保守的过程，外胚层多能性仅限于介于完全间充质和完全上皮状态之间的中间细胞状态。
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 in vitro 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.