title: miR-290/371-Mbd2-Myc circuit regulates glycolytic metabolism to promote pluripotency.
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.
authors.affiliation: 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.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Shengya
authors.initials: S
authors.lastname: Tian
authors.affiliation: 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.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: He
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Xi-Wen
authors.initials: XW
authors.lastname: Wang
authors.affiliation: Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing, China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Kai-Li
authors.initials: KL
authors.lastname: Gu
authors.affiliation: 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.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: De
authors.initials: D
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Lan
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Pathology, School of Medicine, Anhui Medical University, Hefei, China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Cai
authors.affiliation: 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.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yangming
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006019:Glycolysis / Q000235:genetics / Q000502:physiology*; D053858:Metabolic Networks and Pathways / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000201:enzymology* / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C474044:Dgcr8 protein, mouse; C547384:MIRN290 microRNA, mouse; C489326:Mbd2 protein, mouse; D035683:MicroRNAs; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins
keywords: Mbd2; glycolysis; metabolism; microRNA; pluripotency