Metabolic control of primed human pluripotent stem cell fate and function by the miR-200c–SIRT2 axis
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Author(s)
Cha, Young
Han, Min-Joon
Cha, Hyuk-Jin
Burkart, Alison
Jung, Jin Hyuk
Jang, Yongwoo
Kim, Chun-Hyung
Jeong, Ho-Chang
Kim, Byung-Gyu
Kahn, C. Ronald
Date Issued
April 2017
Journal
Nature Cell Biology
Publisher
Nature Publishing Group
Citation
Cha, Young et al. “Metabolic Control of Primed Human Pluripotent Stem Cell Fate and Function by the miR-200c–SIRT2 Axis.” Nature Cell Biology 19, 5 (April 2017): 445–456 © 2017 Macmillan Publishers Limited, part of Springer Nature
Version
Author's final manuscript
Abstract
A hallmark of cancer cells is the metabolic switch from oxidative phosphorylation (OXPHOS) to glycolysis, a phenomenon referred to as the 'Warburg effect', which is also observed in primed human pluripotent stem cells (hPSCs). Here, we report that downregulation of SIRT2 and upregulation of SIRT1 is a molecular signature of primed hPSCs and that SIRT2 critically regulates metabolic reprogramming during induced pluripotency by targeting glycolytic enzymes including aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and enolase. Remarkably, knockdown of SIRT2 in human fibroblasts resulted in significantly decreased OXPHOS and increased glycolysis. In addition, we found that miR-200c-5p specifically targets SIRT2, downregulating its expression. Furthermore, SIRT2 overexpression in hPSCs significantly affected energy metabolism, altering stem cell functions such as pluripotent differentiation properties. Taken together, our results identify the miR-200c-SIRT2 axis as a key regulator of metabolic reprogramming (Warburg-like effect), via regulation of glycolytic enzymes, during human induced pluripotency and pluripotent stem cell function.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1038/NCB3517
