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首页> 外文期刊>EMBO Journal >Small RNA-mediated regulation of iPS cell generation.
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Small RNA-mediated regulation of iPS cell generation.

机译:小rna介导的监管“诱导多能性”细胞的一代。

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摘要

Somatic cells can be reprogrammed to an ES-like state to create induced pluripotent stem cells (iPSCs) by ectopic expression of four transcription factors, Oct4, Sox2, Klf4 and cMyc. Here, we show that cellular microRNAs (miRNAs) regulate iPSC generation. Knock-down of key microRNA pathway proteins resulted in significant decreases in reprogramming efficiency. Three miRNA clusters, miR-17 approximately 92, miR-106b approximately 25 and miR-106a approximately 363, were shown to be highly induced during early reprogramming stages. Several miRNAs, including miR-93 and miR-106b, which have very similar seed regions, greatly enhanced iPSC induction and modulated mesenchymal-to-epithelial transition step in the initiation stage of reprogramming, and inhibiting these miRNAs significantly decreased reprogramming efficiency. Moreover, miR-iPSC clones reached the fully reprogrammed state. Further analysis revealed that Tgfbr2 and p21 are directly targeted by these miRNAs and that siRNA knock-down of both genes indeed enhanced iPSC induction. Here, for the first time, we demonstrate that miR-93 and its family members directly target TGF-beta receptor II to enhance iPSC generation. Overall, we demonstrate that miRNAs function in the reprogramming process and that iPSC induction efficiency can be greatly enhanced by modulating miRNA levels in cells.
机译:精原体细胞可以重新编程国家创建诱导多能干细胞(万能)异位表达的四个转录因子,Oct4、Sox2 Klf4 cMyc。在这里,我们表明,细胞的小分子核糖核酸(microrna)调节iPSC的一代。微通道蛋白导致显著减少重组效率。microrna的集群,mir - 17约92,mir - 106 b大约25和mir - 106约363,被证明是高度在早期诱导重组阶段。mir - 93和mir - 106 b,具有非常相似的种子地区,极大地增强了iPSC诱导和调制mesenchymal-to-epithelial过渡一步重新编程的起始阶段,显著抑制这些microrna重编程效率下降。miR-iPSC克隆达到完全重组状态。p21直接这些microrna的目标这的确siRNA混战的基因增强iPSC感应。时间,我们表明,mir - 93及其家人成员直接目标及受体二世加强iPSC的一代。microrna函数的重编程过程这iPSC感应效率可以大大增强了调制microrna在细胞水平。

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