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

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Title
Metabolic control of primed human pluripotent stem cell fate and function by the miR-200c–SIRT2 axis
Author(s)
Young Cha; Min-Joon Han; Hyuk-Jin Cha; Janet Zoldan; Alison Burkart; Jin Hyuk Jung; Yongwoo Jang; Chun-Hyung Kim; Ho-Chang Jeong; Byung-Gyu Kim; Robert Langer; C. Ronald Kahn; Leonard Guarente; Kwang-Soo Kim
Publication Date
2017-05
Journal
NATURE CELL BIOLOGY, v.19, no.5, pp.445 - 456
Publisher
NATURE PUBLISHING GROUP
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. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
URI
https://pr.ibs.re.kr/handle/8788114/6493
ISSN
1465-7392
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > Journal Papers (저널논문)
Files in This Item:
Nature Cell Biology_2019_Metabolic control of primed human pluripotent stem cell fate and function by the miR-200c–SIRT2 axis.pdfDownload

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