Following implantation, the naive pluripotent epiblast of the mouse blastocyst generates a rosette, undergoes lumenogenesis and forms the primed pluripotent egg cylinder, which is able to generate the embryonic tissues. How pluripotency progression and morphogenesis are linked and whether intermediate pluripotent states exist remain controversial. We identify here a rosette pluripotent state defined by the co-expression of naive factors with the transcription factor OTX2. Downregulation of blastocyst WNT signals drives the transition into rosette pluripotency by inducing OTX2. The rosette then activates MEK signals that induce lumenogenesis and drive progression to primed pluripotency. Consequently, combined WNT and MEK inhibition supports rosette-like stem cells, a self-renewing naive-primed intermediate. Rosette-like stem cells erase constitutive heterochromatin marks and display a primed chromatin landscape, with bivalently marked primed pluripotency genes. Nonetheless, WNT induces reversion to naive pluripotency. The rosette is therefore a reversible pluripotent intermediate whereby control over both pluripotency progression and morphogenesis pivots from WNT to MEK signals.

中文翻译：

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幼稚和启动状态之间的胚胎玫瑰花期多能性的体外捕获和表征。

植入后，小鼠胚泡的幼稚多能表皮细胞生成玫瑰花结，进行光亮作用并形成引发的多能卵瓶，其能够产生胚胎组织。多能性进展和形态发生如何联系以及中间多能性状态是否存在仍存在争议。我们在这里确定了由幼稚因子与转录因子OTX2共表达所定义的玫瑰花多能状态。胚泡WNT信号的下调通过诱导OTX2驱动向玫瑰花多能性的转变。然后，莲座丛激活MEK信号，该信号诱导内腔发生并驱动进展为致敏的多能性。因此，联合的WNT和MEK抑制作用支持玫瑰花样干细胞，一种自我更新的天真启动的中间体。玫瑰花样干细胞擦除组成型异染色质标记并显示引物染色质景观，并带有二价标记的引物多能性基因。尽管如此，WNT仍可诱导其恢复为幼稚的多能性。因此，玫瑰花结是可逆的多能中间物，由此对多能性进展和形态发生的控制都从WNT到MEK信号。