生物
胚胎
形态发生
细胞生物学
瞬态(计算机编程)
遗传学
基因
计算机科学
操作系统
作者
Xuehui Lyu,Yingzi Cui,Yinfei Kong,Min Yang,Hui Shen,Shuyun Liao,Shiyu Li,Chenrui An,Haoyi Wang,Zhe Zhang,Jennie Ong,Li Y,Peng Du
标识
DOI:10.1016/j.molcel.2024.06.005
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI