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

被引：102

作者：

Cao, Yang ^{[1
]}

Guo, Wen-Ting ^{[2
]}

Tian, Shengya ^{[1
]}

He, Xiaoping ^{[1
]}

Wang, Xi-Wen ^{[2
]}

Liu, Xiaomeng ^{[3
]}

Gu, Kai-Li ^{[2
]}

Ma, Xiaoyu ^{[1
]}

Huang, De ^{[1
]}

Hu, Lan ^{[1
]}

Cai, Yongping ^{[4
]}

Zhang, Huafeng ^{[1
]}

Wang, Yangming ^{[2
]}

Gao, Ping ^{[1
]}

机构：

[1] Univ Sci & Technol China, Sch Life Sci, Innovat Ctr Cell Biol, CAS Key Lab Innate Immun & Chron Dis, Hefei 230026, Peoples R China

[2] Peking Univ, Peking Tsinghua Ctr Life Sci, Inst Mol Med, Beijing Key Lab Cardiometab Mol Med, Beijing 100871, Peoples R China

[3] Peking Univ, Coll Life Sci, Biodynam Opt Imaging Ctr, Beijing 100871, Peoples R China

[4] Anhui Med Univ, Sch Med, Dept Pathol, Hefei, Peoples R China

来源：

EMBO JOURNAL | 2015年 / 34卷 / 05期

关键词：

glycolysis; microRNA; Mbd2; metabolism; pluripotency; C-MYC; STEM-CELLS; TRANSCRIPTIONAL NETWORK; MICRORNA BIOGENESIS; CANCER METABOLISM; GENE-REGULATION; SOMATIC-CELLS; SELF-RENEWAL; DICER; DIFFERENTIATION;

D O I：

10.15252/embj.201490441

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：609 / 623

页数：15

共 63 条

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