Epiblast Formation by TEAD-YAP-Dependent Expression of Pluripotency Factors and Competitive Elimination of Unspecified Cells
Epiblast Formation by TEAD-YAP-Dependent Expression of Pluripotency Factors and Competitive Elimination of Unspecified Cells
复制标题
DOI：
10.1016/j.devcel.2019.05.024
复制
发表时间：
2019-07-22
影响因子：
11.8
通讯作者：
Sasaki, Hiroshi
中科院分区：
文献类型：
--
作者：
Hashimoto, Masakazu;Sasaki, Hiroshi
外胚层是在植入前胚胎中首先形成的多能细胞群，其质量对于正常发育至关重要。在这里，我们研究了上胚层形成的机制，发现海马通路转录因子TEAD及其共激活因子雅普调节多能性因子的表达。内细胞团特化后，雅普在细胞核中积累并激活TEAD。TEAD活性是多能性因子强表达所必需的，并且在形成的上胚层中是可变的。显示低TEAD活性的细胞通过细胞竞争从上胚层中消除。多能性因子表达和MYC控制TEAD活性下游的细胞竞争。细胞竞争消除了未指定的细胞，并且是上胚层的适当组织所必需的。这些结果表明，通过TEAD活性诱导多能性因子和通过细胞竞争消除未指定的细胞确保了具有幼稚多能性的上胚层的产生。
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.