Volume 26, No 3, Mar 2016
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 26 Issue 3, March 2016: 350-366 | Open Access
ORIGINAL ARTICLES
Pluripotency-associated miR-290/302 family of microRNAs promote the dismantling of naive pluripotency
Kai-Li Gu1,*, Qiang Zhang1,*, Ying Yan1,*, Ting-Ting Li2,*, Fei-Fei Duan1, Jing Hao1, Xi-Wen Wang1, Ming Shi1, Da-Ren Wu1, Wen-Ting Guo1 and Yangming Wang1
1Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Science, Institute of Molecular Medicine, Peking University, Beijing 100871, China
2Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, Beijing 100083, China
Correspondence: Yangming Wang,(yangming.wang@pku.edu.cn)
The molecular mechanism controlling the dismantling of naive pluripotency is poorly understood. Here we show that microRNAs (miRNAs) have important roles during naive to primed pluripotency transition. Dgcr8−/− embryonic stem cells (ESCs) failed to completely silence the naive pluripotency program, as well as to establish the primed pluripotency program during differentiation. miRNA profiling revealed that expression levels of a large number of miRNAs changed dynamically and rapidly during naive to primed pluripotency transition. Furthermore, a miRNA screen identified numerous miRNAs promoting naive to primed pluripotency transition. Unexpectedly, multiple miRNAs from miR-290 and miR-302 clusters, previously shown as pluripotency-promoting miRNAs, demonstrated the strongest effects in silencing naive pluripotency. Knockout of both miR-290 and miR-302 clusters but not either alone blocked the silencing of naive pluripotency program. Mechanistically, the miR-290/302 family of miRNAs may facilitate the exit of naive pluripotency in part by promoting the activity of MEK pathway and through directly repressing Akt1. Our study reveals miRNAs as an important class of regulators potentiating ESCs to transition from naive to primed pluripotency, and uncovers context-dependent functions of the miR-290/302 family of miRNAs at different developmental stages.
10.1038/cr2016.2
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