MiR-31/SDHA Axis Regulates Reprogramming Efficiency through Mitochondrial Metabolismopen access
- Authors
- Lee, Man Ryul; Mantel, Charlie; Lee, Sang A.; Moon, Sung-Hwan; Broxmeyer, Hal E.
- Issue Date
- Jul-2016
- Publisher
- CELL PRESS
- Citation
- STEM CELL REPORTS, v.7, no.1, pp 1 - 10
- Pages
- 10
- Journal Title
- STEM CELL REPORTS
- Volume
- 7
- Number
- 1
- Start Page
- 1
- End Page
- 10
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/69832
- DOI
- 10.1016/j.stemcr.2016.05.012
- ISSN
- 2213-6711
- 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.
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