Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.
Physiology Graduate Program, Michigan State University, East Lansing, MI 48824, USA.
Development. 2019 Sep 6;146(17):dev179861. doi: 10.1242/dev.179861.
In mice, pluripotent cells are thought to derive from cells buried inside the embryo around the 16-cell stage. is the only pluripotency gene known to be expressed specifically within inside cells at this stage. To understand how pluripotency is established, we therefore investigated the mechanisms regulating the initial activation of expression. Surprisingly, expression initiated normally in the absence of both and (), highlighting differences between embryo and stem cell models of pluripotency. However, we observed precocious ectopic expression of prior to the 16-cell stage in the absence of , and Interestingly, the repression of premature expression was sensitive to LATS kinase activity, even though LATS proteins normally do not limit activity of TEAD4, YAP1 and WWTR1 during these early stages. Finally, we present evidence for direct transcriptional repression of by YAP1, WWTR1 and TEAD4 Taken together, our observations reveal that, while embryos are initially competent to express as early as the four-cell stage, transcriptional repression prevents the premature expression of , thereby restricting the pluripotency program to the stage when inside cells are first created.
在老鼠中，多能细胞被认为来源于胚胎在 16 细胞阶段左右内部的细胞。是已知在这个阶段仅在内部细胞中特异性表达的多能性基因。为了了解多能性是如何建立的，我们因此研究了调节初始激活表达的机制。令人惊讶的是，尽管没有和（），但表达仍正常启动，这突出了胚胎和干细胞多能性模型之间的差异。然而，我们观察到在没有、和的情况下，在 16 细胞阶段之前，过早地出现了的异位表达。有趣的是，抑制过早的表达对 LATS 激酶活性敏感，尽管 LATS 蛋白在这些早期阶段通常不会限制 TEAD4、YAP1 和 WWTR1 的活性。最后，我们提供了证据表明 YAP1、WWTR1 和 TEAD4 直接转录抑制。总的来说，我们的观察结果表明，虽然胚胎最初有能力早在四细胞阶段表达，但转录抑制阻止了的过早表达，从而将多能性程序限制在内部细胞首次产生的阶段。
