Abstract：
During implantation, embryos undergo an unpolarized-to-polarized transition to initiate postimplantation morphogenesis. However, the underlying molecular mechanism is unknown. Here, we identify a transient transcriptional activation governing embryonic morphogenesis and pluripotency transition during implantation. In naive pluripotent embryonic stem cells (ESCs), which represent preimplantation embryos, we find that the microprocessor component DGCR8 can recognize stem-loop structures within nascent mRNAs to sequester transcriptional coactivator FLII to suppress transcription directly. When mESCs exit from naive pluripotency, the ERK/RSK/P70S6K pathway rapidly activates, leading to FLII phosphorylation and disruption of DGCR8/FLII interaction. Phosphorylated FLII can bind to transcription factor JUN, activating cell migration-related genes to establish poised pluripotency akin to implanting embryos. Resequestration of FLII by DGCR8 drives poised ESCs into formative pluripotency. In summary, we identify a DGCR8/FLII/JUN-mediated transient transcriptional activation mechanism. Disruption of this mechanism inhibits naive-poised-formative pluripotency transition and the corresponding unpolarized-to-polarized transition during embryo implantation, which are conserved in mice and humans.
摘要：
在植入过程中,胚胎经历非极化到极化的转变，以启动植入后的形态发生。然而,潜在的分子机制是未知的。这里,我们确定了在植入过程中控制胚胎形态发生和多能性转变的瞬时转录激活。在幼稚多能胚胎干细胞（ESC）中，代表着床前胚胎，我们发现，微处理器成分DGCR8可以识别新生mRNAs内的茎环结构，以隔离转录共激活子FLII，从而直接抑制转录。当mESC从幼稚多能性退出时，ERK/RSK/P70S6K通路快速激活，导致FLII磷酸化和DGCR8/FLII相互作用的破坏。磷酸化FLII可以与转录因子JUN结合，激活细胞迁移相关基因以建立类似于植入胚胎的平衡多能性。DGCR8对FLII的重新测序驱动平衡的ESC进入形成性多能性。总之,我们确定了DGCR8/FLII/JUN介导的瞬时转录激活机制。这种机制的破坏抑制了胚胎植入过程中幼稚形成的多能性转变和相应的非极化到极化的转变，在小鼠和人类中都是保守的。
