Functional Screen Reveals Essential Roles of MiR-27a/24 in Differentiation of Embryonic Stem Cells

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2014 Dec 19

PMID 25519956

Citations 37

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

Affiliations

Soon will be listed here.

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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