AI Article Synopsis
- Metabolism is altered when somatic cells are converted into induced pluripotent stem cells (iPSCs), leading them to rely more on anaerobic glycolysis rather than mitochondrial respiration.
- MicroRNA 31 (miR-31) plays a key role in this process by suppressing the expression of succinate dehydrogenase complex subunit A (SDHA), which is essential for mitochondrial function.
- Overexpressing miR-31, especially when combined with Yamanaka factors, significantly enhances the reprogramming efficiency of iPSCs by promoting a shift towards glycolytic metabolism, highlighting the importance of metabolic changes during the reprogramming process.
Article 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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944586 | PMC |
| http://dx.doi.org/10.1016/j.stemcr.2016.05.012 | DOI Listing |
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