The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiation
The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiation
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DOI：
10.1101/gad.1903310
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发表时间：
2010-06-01
影响因子：
10.5
通讯作者：
Guan, Kun-Liang
中科院分区：
文献类型：
--
作者：
Lian, Ian;Kim, Joungmok;Guan, Kun-Liang
Yes相关蛋白（雅普）是一种有效的转录辅激活因子，通过与TEAD转录因子结合发挥作用，在器官大小调节中起重要作用。雅普被磷酸化并被Hippo肿瘤抑制途径的关键组分Lats激酶抑制。升高的雅普蛋白水平和基因扩增与人类癌症有关。在这项研究中，我们报告说，雅普在胚胎干细胞（ES）分化过程中失活，蛋白水平下降和磷酸化增加。因此，雅普在诱导多能干细胞（iPS）重编程过程中升高。雅普敲低导致ES细胞多能性的丧失，而雅普的异位表达阻止ES细胞体外分化并甚至在分化条件下维持干细胞表型。此外，雅普直接与已知对干细胞重要的大量基因的启动子结合并刺激它们的表达。我们的观察建立了雅普在维持干细胞多能性中的关键作用。
Yes-associated protein (YAP) is a potent transcription coactivator acting via binding to the TEAD transcription factor, and plays a critical role in organ size regulation. YAP is phosphorylated and inhibited by the Lats kinase, a key component of the Hippo tumor suppressor pathway. Elevated YAP protein levels and gene amplification have been implicated in human cancer. In this study, we report that YAP is inactivated during embryonic stem (ES) cell differentiation, as indicated by decreased protein levels and increased phosphorylation. Consistently, YAP is elevated during induced pluripotent stem (iPS) cell reprogramming. YAP knockdown leads to a loss of ES cell pluripotency, while ectopic expression of YAP prevents ES cell differentiation in vitro and maintains stem cell phenotypes even under differentiation conditions. Moreover, YAP binds directly to promoters of a large number of genes known to be important for stem cells and stimulates their expression. Our observations establish a critical role of YAP in maintaining stem cell pluripotency.