MiR-31/SDHA Axis Regulates Reprogramming Efficiency through Mitochondrial Metabolism

Man Ryul Lee, Charlie Mantel, Sang A. Lee, Sung Hwan Moon, Hal E. Broxmeyer

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalStem Cell Reports
Volume7
Issue number1
DOIs
StatePublished - Jul 12 2016

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ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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