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Functional screen reveals essential roles of miR‐27a/24 in differentiation of embryonic stem cells
Author(s) -
Ma Yanni,
Yao Nan,
Liu Guang,
Dong Lei,
Liu Yufang,
Zhang Meili,
Wang Fang,
Wang Bin,
Wei Xueju,
Dong He,
Wang Lanlan,
Ji Shaowei,
Zhang Junwu,
Wang Yangming,
Huang Yue,
Yu Jia
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201489957
Subject(s) - biology , embryonic stem cell , reprogramming , microrna , microbiology and biotechnology , cellular differentiation , gene silencing , stem cell , somatic cell , genetics , cell , gene
Micro RNA s play important roles in controlling the embryonic stem cell ( ESC ) state. Although much is known about micro RNA s maintaining ESC state, micro RNA s that are responsible for promoting ESC differentiation are less reported. Here, by screening 40 micro RNA s pre‐selected by their expression patterns and predicted targets in Dgcr8 ‐null ESC s, we identify 14 novel differentiation‐associated micro RNA s. 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 ESC s 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 micro RNA s responsible for ESC differentiation.