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Metabolic control of primed human pluripotent stem cell fate and function by the miR-200c-SIRT2 axis

Title
Metabolic control of primed human pluripotent stem cell fate and function by the miR-200c-SIRT2 axis
Author
장용우
Keywords
ENERGY-METABOLISM; PROFILING REVEALS; UP-REGULATION; EXPRESSION; DIFFERENTIATION; ACETYLATION; MOUSE; GENERATION; DISTINCT; GENES
Issue Date
2017-05
Publisher
NATURE PUBLISHING GROUP
Citation
NATURE CELL BIOLOGY, v. 19, no. 5, page. 445-445
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.
URI
https://www.nature.com/articles/ncb3517https://repository.hanyang.ac.kr/handle/20.500.11754/114211
ISSN
1465-7392; 1476-4679
DOI
10.1038/ncb3517
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > ELECTRICAL AND BIOMEDICAL ENGINEERING(전기·생체공학부) > Articles
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