The foundations of mammalian development lie in a cluster of embryonic epiblast stem cells. In response to extracellular matrix signalling, these cells undergo epithelialization and create an apical surface in contact with a cavity, a fundamental event for all subsequent development. Concomitantly, epiblast cells transit through distinct pluripotent states, before lineage commitment at gastrulation. These pluripotent states have been characterized at the molecular level, but their biological importance remains unclear. Here we show that exit from an unrestricted naive pluripotent state is required for epiblast epithelialization and generation of the pro-amniotic cavity in mouse embryos. Embryonic stem cells locked in the naive state are able to initiate polarization but fail to undergo lumenogenesis. Mechanistically, exit from naive pluripotency activates an Oct4-governed transcriptional program that results in expression of glycosylated sialomucin proteins and the vesicle tethering and fusion events of lumenogenesis. Similarly, exit of epiblasts from naive pluripotency in cultured human post-implantation embryos triggers amniotic cavity formation and developmental progression. Our results add tissue-level architecture as a new criterion for the characterization of different pluripotent states, and show the relevance of transitions between these states during development of the mammalian embryo.

中文翻译：

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多能状态转换协调小鼠和人类胚胎的形态发生


哺乳动物发育的基础在于胚胎外胚层干细胞簇。为了响应细胞外基质信号传导，这些细胞经历上皮化并形成与空腔接触的顶端表面，这是所有后续发育的基本事件。与此同时，在原肠胚形成时的谱系定型之前，外胚层细胞会经历不同的多能状态。这些多能状态已在分子水平上得到表征，但其生物学重要性仍不清楚。在这里，我们表明，在小鼠胚胎中，外胚层上皮化和前羊膜腔的生成需要脱离不受限制的幼稚多能状态。锁定在幼稚状态的胚胎干细胞能够启动极化，但无法进行腔生成。从机制上讲，退出幼稚多能性会激活 Oct4 控制的转录程序，导致糖基化唾液粘蛋白​​的表达以及腔生成的囊泡束缚和融合事件。同样，在培养的人类植入后胚胎中，外胚层从幼稚多能性中退出会触发羊膜腔的形成和发育进程。我们的结果增加了组织水平结构作为表征不同多能状态的新标准，并显示了哺乳动物胚胎发育过程中这些状态之间转变的相关性。