Functional screen reveals essential roles of miR‐27a/24 in differentiation of embryonic stem cells |
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| Authors: | Yanni Ma Nan Yao Guang Liu Lei Dong Yufang Liu Meili Zhang Fang Wang Bin Wang Xueju Wei He Dong Lanlan Wang Shaowei Ji Junwu Zhang Yangming Wang Yue Huang Jia Yu |
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| Institution: | 1. State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China;2. Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China;3. Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China;4. Peking‐Tsinghua Joint Center for Life Sciences, Institute of Molecular Medicine, Peking University, Beijing, China |
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| Abstract: | MicroRNAs play important roles in controlling the embryonic stem cell (ESC) state. Although much is known about microRNAs maintaining ESC state, microRNAs that are responsible for promoting ESC differentiation are less reported. Here, by screening 40 microRNAs pre-selected by their expression patterns and predicted targets in Dgcr8-null ESCs, we identify 14 novel differentiation-associated microRNAs. Among them, miR-27a and miR-24, restrained by c-Myc in ESC, exert their roles of silencing self-renewal through directly targeting several important pluripotency-associated factors, such as Oct4, Foxo1 and Smads. CRISPR/Cas9-mediated knockout of all miR-27/24 in ESCs leads to serious deficiency in ESC differentiation in vitro and in vivo. Moreover, depleting of them in mouse embryonic fibroblasts can evidently promote somatic cell reprogramming. Altogether, our findings uncover the essential role of miR-27 and miR-24 in ESC differentiation and also demonstrate novel microRNAs responsible for ESC differentiation. |
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| Keywords: | c-Myc differentiation embryonic stem cells iPSC generation microRNA |
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