摘要
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.
植入后，小鼠胚泡的naive多能上胚层产生玫瑰花结结构，经历腔发生并形成primed多能卵圆柱体，能够产生胚胎组织。多能性进展和形态发生如何联系以及是否存在中间多能性状态仍然存在争议。我们在这里确定了由naive因子与转录因子 OTX2 的共表达定义的花环样多能状态。胚泡 WNT 信号的下调通过诱导 OTX2 驱动向花环样多能状态的转变。然后，玫瑰花结激活 MEK 信号，诱导腔发生并推动进展为primed的多能性。因此，联合 WNT 和 MEK 抑制支持花环样干细胞，一种自我更新的naive-primed中间体。类似玫瑰花结的干细胞消除了组成型异染色质标记，并显示出primed的染色质景观，并带有二价标记的primed多能性基因。尽管如此，WNT 诱导恢复到naive的多能性。因此，玫瑰花结是一种可逆的多能中间体，由此对多能性进展和形态发生的控制从 WNT 信号转为 MEK 信号。
笔记
