Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells.
Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells.
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DOI：
10.1038/nbt.1862
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发表时间：
2011-05
影响因子：
46.9
通讯作者：
中科院分区：
文献类型：
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作者：
胚胎干细胞特异性细胞周期调控（ESCC）微小RNA（miRNA）家族可增强小鼠胚胎成纤维细胞重编程为诱导多能干细胞的能力。在此我们表明，人类ESCC miRNA的同源物hsa - miR - 302b和hsa - miR - 372可促进人类体细胞重编程。此外，这些miRNA抑制多个靶基因，单个靶基因的下调仅部分重现了miRNA的总体效应。这些靶基因调控多种细胞过程，包括细胞周期、上皮 - 间质转化（EMT）、表观遗传调控和囊泡运输。ESCC miRNA在调控独特的胚胎干细胞周期中具有已知作用。我们发现它们还可提高重编程过程中间质 - 上皮转化的动力学，并阻断转化生长因子β（TGFβ）诱导的人类上皮细胞的上皮 - 间质转化。这些结果表明，ESCC miRNA通过作用于多个下游通路促进去分化。我们提出，单个miRNA通常通过众多通路协同作用来调控和决定细胞命运。
The embryonic stem cell–specific cell cycle–regulating (ESCC) family of microRNAs (miRNAs) enhances reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells. Here we show that the human ESCC miRNA orthologs hsa-miR-302b and hsa-miR-372 promote human somatic cell reprogramming. Furthermore, these miRNAs repress multiple target genes, with downregulation of individual targets only partially recapitulating the total miRNA effects. These targets regulate various cellular processes, including cell cycle, epithelial-mesenchymal transition (EMT), epigenetic regulation and vesicular transport. ESCC miRNAs have a known role in regulating the unique embryonic stem cell cycle. We show that they also increase the kinetics of mesenchymal-epithelial transition during reprogramming and block TGFβ-induced EMT of human epithelial cells. These results demonstrate that the ESCC miRNAs promote dedifferentiation by acting on multiple downstream pathways. We propose that individual miRNAs generally act through numerous pathways that synergize to regulate and enforce cell fate decisions.
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DOI：
10.4161/cc.8.22.10033
发表时间：
2009-11-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Qi J;Yu JY;Shcherbata HR;Mathieu J;Wang AJ;Seal S;Zhou W;Stadler BM;Bourgin D;Wang L;Nelson A;Ware C;Raymond C;Lim LP;Magnus J;Ivanovska I;Diaz R;Ball A;Cleary MA;Ruohola-Baker H
通讯作者：
Ruohola-Baker H
影响因子：
48
作者：
Lin, Tongxiang;Ambasudhan, Rajesh;Yuan, Xu;Li, Wenlin;Hilcove, Simon;Abujarour, Ramzey;Lin, Xiangyi;Hahm, Heung Sik;Hao, Ergeng;Hayek, Alberto;Ding, Sheng
通讯作者：
Ding, Sheng
影响因子：
4.5
作者：
Lin, Shi-Lung;Chang, Donald C.;Ying, Shao-Yao
通讯作者：
Ying, Shao-Yao
影响因子：
7
作者：
Morin, Ryan D.;O'Connor, Michael D.;Marra, Marco A.
通讯作者：
Marra, Marco A.
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