TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors.
TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors.
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DOI：
10.1038/ncb3160
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发表时间：
2015-05
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
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作者：
人类器官发生的基因组调控程序知之甚少。胰腺的发育，特别是胰腺再生，癌症和糖尿病的关键影响。我们现在的特点是胚胎多能祖细胞，引起所有胰腺上皮谱系的监管景观。使用人胚胎胰腺和胚胎干细胞衍生的祖细胞，我们确定了阶段特异性转录本和相关的增强子，其中许多是共同占用的转录因子是必不可少的胰腺发育。我们进一步表明，TEAD 1，海马信号效应，是胰腺祖细胞增强子的转录因子组合密码的一个组成部分。TEAD及其共激活因子雅普激活关键的胰腺信号传导介质和转录因子，并调节胰腺祖细胞的扩增。因此，这项工作揭示了TEAD和雅普作为多能胰腺祖细胞的信号响应调节剂的核心作用，并为人类胰腺胚胎发育的研究提供了资源。
The genomic regulatory programs that underlie human organogenesis are poorly understood. Pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer, and diabetes. We have now characterized the regulatory landscape of embryonic multipotent progenitor cells that give rise to all pancreatic epithelial lineages. Using human embryonic pancreas and embryonic stem cell-derived progenitors we identify stage-specific transcripts and associated enhancers, many of which are co-occupied by transcription factors that are essential for pancreas development. We further show that TEAD1, a Hippo signaling effector, is an integral component of the transcription factor combinatorial code of pancreatic progenitor enhancers. TEAD and its coactivator YAP activate key pancreatic signaling mediators and transcription factors, and regulate the expansion of pancreatic progenitors. This work therefore uncovers a central role of TEAD and YAP as signal-responsive regulators of multipotent pancreatic progenitors, and provides a resource for the study of embryonic development of the human pancreas.
基于器官发生网络的比较转录组分析，用于了解早期人类体内和体外发育。
影响因子：
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作者：
Fang H;Jin W;Yang Y;Jin Y;Zhang J;Wang K
通讯作者：
Wang K