DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal
DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal
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DOI：
10.1038/ng1969
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发表时间：
2007-03-01
期刊：
影响因子：
30.8
通讯作者：
Blelloch, Robert
中科院分区：
文献类型：
--
作者：
Wang, Yangming;Medvid, Rostislav;Blelloch, Robert
控制胚胎干细胞分化的分子调控机制仍知之甚少。DGCR 8是一种RNA结合蛋白，它协助RNase III酶Drosha加工microRNA（miRNA），一种小RNA的亚类。在这里，我们通过建立Dgcr 8敲除模型来研究miRNAs在ES细胞分化中的作用。小鼠敲除ES细胞的分析表明，DGCR 8对于miRNA的生物合成是必需的。在诱导分化时，DGCR 8缺陷型ES细胞不完全下调多能性标志物并保留产生ES细胞集落的能力;然而，它们确实表达一些分化标志物。这种表型与Dicer 1敲除细胞的表型不同，表明Dicer在ES细胞功能中具有不依赖于miRNA的作用。我们的研究结果表明，miRNAs的功能沉默的ES细胞自我更新，通常发生的诱导分化。
The molecular controls that govern the differentiation of embryonic stem (ES) cells remain poorly understood. DGCR8 is an RNA-binding protein that assists the RNase III enzyme Drosha in the processing of microRNAs (miRNAs), a subclass of small RNAs. Here we study the role of miRNAs in ES cell differentiation by generating a Dgcr8 knockout model. Analysis of mouse knockout ES cells shows that DGCR8 is essential for biogenesis of miRNAs. On the induction of differentiation, DGCR8-deficient ES cells do not fully downregulate pluripotency markers and retain the ability to produce ES cell colonies; however, they do express some markers of differentiation. This phenotype differs from that reported for Dicer1 knockout cells, suggesting that Dicer has miRNA-independent roles in ES cell function. Our findings indicate that miRNAs function in the silencing of ES cell self-renewal that normally occurs with the induction of differentiation.