title: MiR-31/SDHA Axis Regulates Reprogramming Efficiency through Mitochondrial Metabolism.
abstract: Metabolism is remodeled when somatic cells are reprogrammed into induced pluripotent stem cells (iPSCs), but the majority of iPSCs are not fully reprogrammed. In a shift essential for reprogramming, iPSCs use less mitochondrial respiration but increased anaerobic glycolysis for bioenergetics. We found that microRNA 31 (miR-31) suppressed succinate dehydrogenase complex subunit A (SDHA) expression, vital for mitochondrial electron transport chain (ETC) complex II. MiR-31 overexpression in partially reprogrammed iPSCs lowered SDHA expression levels and oxygen consumption rates to that of fully reprogrammed iPSCs, but did not increase the proportion of fully reprogrammed TRA1-60(+) cells in colonies unless miR-31 was co-transduced with Yamanaka factors, which resulted in a 2.7-fold increase in full reprogramming. Thus switching from mitochondrial respiration to glycolytic metabolism through regulation of the miR-31/SDHA axis is critical for lowering the reprogramming threshold. This is supportive of multi-stage reprogramming whereby metabolic remodeling is fundamental.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, 950 West Walnut Street, Indianapolis, IN 46202-5181, USA; Soonchunhyang Institute of Medi-bio Science, Institute of Tissue Regeneration, Soon Chun Hyang University, Asan-si, 31151 Chungcheongnam-do, Republic of Korea. Electronic address: leeman@sch.ac.kr.
authors.forename: Man Ryul
authors.initials: MR
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, 950 West Walnut Street, Indianapolis, IN 46202-5181, USA.
authors.forename: Charlie
authors.initials: C
authors.lastname: Mantel
authors.affiliation: Soonchunhyang Institute of Medi-bio Science, Institute of Tissue Regeneration, Soon Chun Hyang University, Asan-si, 31151 Chungcheongnam-do, Republic of Korea.
authors.forename: Sang A
authors.initials: SA
authors.lastname: Lee
authors.affiliation: School of Medicine, Kon Kuk University, 05029 Seoul, Republic of Korea.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Moon
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, 950 West Walnut Street, Indianapolis, IN 46202-5181, USA. Electronic address: hbroxmey@iupui.edu.
authors.forename: Hal E
authors.initials: HE
authors.lastname: Broxmeyer
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D065150:Cellular Reprogramming / Q000235:genetics; D042963:Electron Transport Complex II / Q000235:genetics* / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D042963:Electron Transport Complex II; C511268:SDHA protein, human