GATA6 is essential for endoderm formation from human pluripotent stem cells.
GATA6 is essential for endoderm formation from human pluripotent stem cells.
复制标题
DOI：
10.1242/bio.026120
复制
发表时间：
2017-07-15
期刊：
影响因子：
2.4
通讯作者：
Duncan SA
中科院分区：
文献类型：
--
作者：
Fisher JB;Pulakanti K;Rao S;Duncan SA
已经建立了将人类多能干细胞直接分化为多种细胞类型的方案，包括内胚层及其衍生物。这种分化模型对于研究指导人类发育过程的分子机制很有用。使用定向分化方案与 shRNA 去除相结合，我们试图了解 GATA6 在调节从多能性到定形内胚层的最早转变中的作用。我们发现内胚层形成过程中 GATA6 的缺失会导致新生内胚层细胞凋亡，同时内胚层基因表达丧失。我们通过染色质免疫沉淀和 DNA 测序表明，GATA6 直接与编码内胚层分化必需的转录因子的多个基因结合。我们的数据支持这样的观点，即GATA6是通过直接控制内胚层基因表达从多能干细胞形成人定形内胚层的中央调节因子。摘要：利用 huESC 的分化作为内胚层形成的模型，我们揭示了转录因子 GATA6 调节内胚层基因表达的开始，并且是其活力所必需的。
Protocols have been established that direct differentiation of human pluripotent stem cells into a variety of cell types, including the endoderm and its derivatives. This model of differentiation has been useful for investigating the molecular mechanisms that guide human developmental processes. Using a directed differentiation protocol combined with shRNA depletion we sought to understand the role of GATA6 in regulating the earliest switch from pluripotency to definitive endoderm. We reveal that GATA6 depletion during endoderm formation results in apoptosis of nascent endoderm cells, concomitant with a loss of endoderm gene expression. We show by chromatin immunoprecipitation followed by DNA sequencing that GATA6 directly binds to several genes encoding transcription factors that are necessary for endoderm differentiation. Our data support the view that GATA6 is a central regulator of the formation of human definitive endoderm from pluripotent stem cells by directly controlling endoderm gene expression. Summary: Using the differentiation of huESCs as a model for endoderm formation, we reveal that the transcription factor GATA6 regulates the onset of endoderm gene expression and is required for its viability.
登录
查看更多内容
影响因子：
11.8
作者：
Bjornson, CRR;Griffin, KJR;Kimelman, D
通讯作者：
Kimelman, D
影响因子：
64.8
作者：
Bouwmeester, T;Kim, SH;DeRobertis, EM
通讯作者：
DeRobertis, EM
影响因子：
16
作者：
Cirillo, LA;Zaret, KS
通讯作者：
Zaret, KS
影响因子：
2.6
作者：
Belo, JA;Bouwmeester, T;De Robertis, EM
通讯作者：
De Robertis, EM
DOI：
10.1242/dev.014357
发表时间：
2008-02
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Arnold SJ;Hofmann UK;Bikoff EK;Robertson EJ
通讯作者：
Robertson EJ