Small RNA-mediated regulation of iPS cell generation.
Small RNA-mediated regulation of iPS cell generation.
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DOI：
10.1038/emboj.2011.2
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发表时间：
2011-03-02
期刊：
影响因子：
11.4
通讯作者：
Rana, Tariq M.
中科院分区：
文献类型：
--
作者：
Li, Zhonghan;Yang, Chao-Shun;Nakashima, Katsuhiko;Rana, Tariq M.
诱导多能干细胞的产生受到体细胞重编程效率低的限制。本研究发现，三组mirna通过靶向TGF-β和p53通路，从而抑制重编程过程，从而提高重编程效率。体细胞可以通过异位表达Oct4、Sox2、Klf4和cMyc四种转录因子，重编程为es样状态，产生诱导多能干细胞（iPSCs）。在这里，我们发现细胞microRNAs （miRNAs）调节iPSC的产生。关键microRNA通路蛋白的敲除导致重编程效率显著降低。三个miRNA簇，miR-17 ~ 92， miR-106b ~ 25和miR-106a ~ 363，被证明在早期重编程阶段高度诱导。几种mirna，包括miR-93和miR-106b，具有非常相似的种子区，极大地增强了iPSC诱导，并调节了重编程起始阶段的间质到上皮的转变步骤，抑制这些mirna可显著降低重编程效率。此外，miR-iPSC克隆达到完全重编程状态。进一步的分析显示Tgfbr2和p21是这些mirna的直接靶标，并且这两个基因的siRNA敲除确实增强了iPSC诱导。在这里，我们首次证明miR-93及其家族成员直接靶向TGF-β受体II来促进iPSC的生成。总之，我们证明了miRNA在重编程过程中发挥作用，并且通过调节细胞中的miRNA水平可以大大提高iPSC诱导效率。
The generation of induced pluripotent stem cells is limited by the low reprogramming efficiency of somatic cells. Here, three clusters of miRNAs are shown to enhance reprogramming efficiency by targeting the TGF-β and p53 pathways, which inhibit the process. 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∼92, miR-106b∼25 and miR-106a∼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-β 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.
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影响因子：
64.5
作者：
Hanna, Jacob;Markoulaki, Styliani;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
DOI：
10.1016/j.cub.2009.08.025
发表时间：
2009-11-03
期刊：
Current biology : CB
影响因子：
--
作者：
Maherali N;Hochedlinger K
通讯作者：
Hochedlinger K
影响因子：
16
作者：
Lal A;Navarro F;Maher CA;Maliszewski LE;Yan N;O'Day E;Chowdhury D;Dykxhoorn DM;Tsai P;Hofmann O;Becker KG;Gorospe M;Hide W;Lieberman J
通讯作者：
Lieberman J
影响因子：
23.9
作者：
Ichida JK;Blanchard J;Lam K;Son EY;Chung JE;Egli D;Loh KM;Carter AC;Di Giorgio FP;Koszka K;Huangfu D;Akutsu H;Liu DR;Rubin LL;Eggan K
通讯作者：
Eggan K
间充质到上皮的转变启动并且是小鼠成纤维细胞核重编程所必需的
影响因子：
23.9
作者：
Li, Ronghui;Liang, Jialiang;Pei, Duanqing
通讯作者：
Pei, Duanqing