Lee, Man RyulMantel, CharlieLee, Sang A.Moon, Sung-HwanBroxmeyer, Hal E.2017-05-032017-05-032016-07-12Lee, M. R., Mantel, C., Lee, S. A., Moon, S.-H., & Broxmeyer, H. E. (2016). MiR-31/SDHA Axis Regulates Reprogramming Efficiency through Mitochondrial Metabolism. Stem Cell Reports, 7(1), 1–10. http://doi.org/10.1016/j.stemcr.2016.05.0122213-6711https://hdl.handle.net/1805/12435Metabolism 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.en-USAttribution-NonCommercial-NoDerivs 3.0 United StatesInduced Pluripotent Stem Cellssomatic cellsmiR-31, humanmicroRNA-31, humansuccinate dehydrogenase complex, subunit A, flavoprotein (Fp) protein, humanArticle