Myc represses primitive endoderm differentiation in pluripotent stem cells.
Myc represses primitive endoderm differentiation in pluripotent stem cells.
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DOI：
10.1016/j.stem.2010.06.023
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发表时间：
2010-09-03
期刊：
影响因子：
23.9
通讯作者：
Dalton S
中科院分区：
文献类型：
--
作者：
Smith KN;Singh AM;Dalton S
诱导多能干细胞（iPSC）的产生提供了一种新的方法，以促进研究控制干细胞多能性和自我更新的机制。Myc以前已被证明是关键的小鼠胚胎干细胞（mESC）的维护，同时也提高了定向重编程的成纤维细胞的基因表达的影响广泛的变化。尽管有几项研究确定了体内靶基因，但Myc调节多能性的确切机制仍然未知。在这里，我们报告说，在iPSCs和ESCs中的c-和N-MYC的共缺失导致它们自发分化为原始内胚层。我们表明，Myc通过抑制原始内胚层主调节因子GATA 6维持多能性，同时还通过调节mir-17-92 miRNA簇促进细胞周期控制。我们的研究结果表明，不可或缺的要求c-或N-myc的多能性超出增殖和代谢控制。
The generation of induced pluripotent stem cells (iPSCs) provides a novel method to facilitate investigations into the mechanisms that control stem cell pluripotency and self-renewal. Myc has previously been shown to be critical for murine embryonic stem cell (mESC) maintenance, while also enhancing directed reprogramming of fibroblasts by effecting widespread changes in gene expression. Despite several studies identifying in vivo target genes, the precise mechanism by which Myc regulates pluripotency remains unknown. Here we report that co-deletion of c- and N-MYC in iPSCs and ESCs results in their spontaneous differentiation to primitive endoderm. We show that Myc sustains pluripotency through repression of the primitive endoderm master regulator GATA6, while also contributing to cell cycle control by regulation of the mir-17-92 miRNA cluster. Our findings demonstrate the indispensable requirement for c- or N-myc in pluripotency beyond proliferative and metabolic control.
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