Laboratory for Embryogenesis, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
Laboratory for Embryogenesis, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
Dev Cell. 2019 Jul 22;50(2):139-154.e5. doi: 10.1016/j.devcel.2019.05.024. Epub 2019 Jun 13.
The epiblast is a pluripotent cell population first formed in preimplantation embryos, and its quality is important for proper development. Here, we examined the mechanisms of epiblast formation and found that the Hippo pathway transcription factor TEAD and its coactivator YAP regulate expression of pluripotency factors. After specification of the inner cell mass, YAP accumulates in the nuclei and activates TEAD. TEAD activity is required for strong expression of pluripotency factors and is variable in the forming epiblast. Cells showing low TEAD activity are eliminated from the epiblast through cell competition. Pluripotency factor expression and MYC control cell competition downstream of TEAD activity. Cell competition eliminates unspecified cells and is required for proper organization of the epiblast. These results suggest that induction of pluripotency factors by TEAD activity and elimination of unspecified cells via cell competition ensure the production of an epiblast with naive pluripotency.
内细胞团首先在胚胎着床前形成多能细胞群体，其质量对于正常发育很重要。在这里，我们研究了内细胞团形成的机制，发现 Hippo 通路转录因子 TEAD 及其共激活因子 YAP 调节多能性因子的表达。在内细胞团特化后，YAP 积累在细胞核中并激活 TEAD。TEAD 活性对于多能性因子的强烈表达是必需的，并且在形成的内细胞团中是可变的。显示低 TEAD 活性的细胞通过细胞竞争从内细胞团中被清除。多能性因子表达和 MYC 控制 TEAD 活性下游的细胞竞争。细胞竞争消除未特化的细胞，对于内细胞团的正确组织是必需的。这些结果表明，TEAD 活性诱导多能性因子的表达和通过细胞竞争消除未特化的细胞，确保产生具有原始多能性的内细胞团。
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