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EMBO J. 2015 Mar 4;34(5):609-23. doi: 10.15252/embj.201490441. Epub 2015 Jan 20.

miR-290/371-Mbd2-Myc circuit regulates glycolytic metabolism to promote pluripotency.

Author information

1
The CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei, China.
2
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Institute of Molecular Medicine, Peking University, Beijing, China.
3
Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing, China.
4
Department of Pathology, School of Medicine, Anhui Medical University, Hefei, China.
5
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Institute of Molecular Medicine, Peking University, Beijing, China yangming.wang@pku.edu.cn pgao2@ustc.edu.cn.
6
The CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei, China yangming.wang@pku.edu.cn pgao2@ustc.edu.cn.

Abstract

Enhanced glycolysis is a main feature of pluripotent stem cells (PSCs) and is proposed to be important for the maintenance and induction of pluripotency. The molecular mechanism underlying enhanced glycolysis in PSCs is not clear. Using Dgcr8-/- mouse embryonic stem cells (ESCs) that lack mature miRNAs, we found that miR-290 cluster of miRNAs stimulates glycolysis by upregulating glycolytic enzymes Pkm2 and Ldha, which are also essential for the induction of pluripotency during reprogramming. Mechanistically, we identified Mbd2, a reader for methylated CpGs, as the target of miR-290 cluster that represses glycolysis and reprogramming. Furthermore, we discovered Myc as a key target of Mbd2 that controls metabolic switch in ESCs. Importantly, we demonstrated that miR-371 cluster, a human homolog of miR-290 cluster, stimulates glycolysis to promote the reprogramming of human fibroblasts. Hence, we identified a previously unappreciated mechanism by which miR-290/371 miRNAs orchestrate epigenetic, transcriptional and metabolic networks to promote pluripotency in PSCs and during reprogramming.

KEYWORDS:

Mbd2; glycolysis; metabolism; microRNA; pluripotency

PMID:
25603933
PMCID:
PMC4365031
DOI:
10.15252/embj.201490441
[Indexed for MEDLINE]
Free PMC Article

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