Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency.
Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency.
复制标题
DOI：
10.1016/j.stem.2011.03.001
复制
发表时间：
2011-04-08
期刊：
影响因子：
23.9
通讯作者：
Morrisey, Edward E.
中科院分区：
文献类型：
--
作者：
Anokye-Danso, Frederick;Trivedi, Chinmay M.;Juhr, Denise;Gupta, Mudit;Cui, Zheng;Tian, Ying;Zhang, Yuzhen;Yang, Wenli;Gruber, Peter J.;Epstein, Jonathan A.;Morrisey, Edward E.
基于转录因子的细胞重编程开辟了将体细胞转化为多能状态的途径，但由于需要转录因子和该过程的相对低效而面临限制。我们在这里展示了miR 302/367簇的表达快速有效地将小鼠和人类体细胞重编程为iPS状态，而不需要外源转录因子。这种基于miRNA的重编程方法比标准的Oct 4/Sox 2/Klf 4/Myc介导的方法更有效两个数量级。小鼠和人miR 302/367 iPS细胞显示出与Oct 4/Sox 2/Klf 4/Myc-iPS细胞相似的特征，包括多能性标志物表达、畸胎瘤形成，以及对于小鼠细胞，嵌合体贡献和种系贡献。我们发现miR 367表达是miR 302/367介导的重编程所必需的，并激活Oct 4基因表达，并且还需要抑制Hdac 2。因此，我们的数据表明，miRNA和Hdac介导的途径可以以强有力的方式合作，将体细胞重编程为多能性。
Transcription factor-based cellular reprogramming has opened the way to converting somatic cells to a pluripotent state, but has faced limitations resulting from the requirement for transcription factors and the relative inefficiency of the process. We show here that expression of the miR302/367 cluster rapidly and efficiently reprograms mouse and human somatic cells to an iPS state without a requirement for exogenous transcription factors. This miRNA-based reprogramming approach is two orders of magnitude more efficient than standard Oct4/Sox2/Klf4/Myc-mediated methods. Mouse and human miR302/367 iPS cells display similar characteristics to Oct4/Sox2/Klf4/Myc-iPS cells, including pluripotency marker expression, teratoma formation, and, for mouse cells, chimera contribution and germline contribution. We found that miR367 expression is required for miR302/367-mediated reprogramming and activates Oct4 gene expression, and that suppression of Hdac2 is also required. Thus, our data show that miRNA and Hdac-mediated pathways can co-operate in a powerful way to reprogram somatic cells to pluripotency.
登录
查看更多内容
影响因子：
4.8
作者：
Moretti, Alessandra;Bellin, Milena;Laugwitz, Karl-Ludwig
通讯作者：
Laugwitz, Karl-Ludwig
影响因子：
64.5
作者：
Kim, Jonghwan;Chu, Jianlin;Orkin, Stuart H.
通讯作者：
Orkin, Stuart H.
影响因子：
10.5
作者：
Babiarz, Joshua E.;Ruby, J. Graham;Blelloch, Robert
通讯作者：
Blelloch, Robert
影响因子：
4.8
作者：
Trivedi, Chinmay M.;Lu, Min Min;Epstein, Jonathan A.
通讯作者：
Epstein, Jonathan A.
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C