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한빛사 논문

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Harvard Medical School

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Nat. Cell Biol., Published online 24 April 2017, doi:10.1038/ncb3517 Metabolic control of primed human pluripotent stem cell fate and function by the miR-200c–SIRT2 axis

Young Cha^1,7, Min-Joon Han^1,7,8, Hyuk-Jin Cha^2,7, Janet Zoldan^3,8, Alison Burkart⁴, Jin Hyuk Jung¹, Yongwoo Jang¹, Chun-Hyung Kim¹, Ho-Chang Jeong², Byung-Gyu Kim⁵, Robert Langer³, C. Ronald Kahn⁴, Leonard Guarente⁶ and Kwang-Soo Kim^1,9
¹Molecular Neurobiology Laboratory, Department of Psychiatry and McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, Massachusetts 02478, USA. ²College of Natural Sciences, Department of Life Sciences, Sogang University, Seoul 04107, Korea. ³Department of Chemical Engineering, David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, Massachusetts 02139, USA. ⁴Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA. ⁵Center for Genomic Integrity Institute for Basic Science, Ulsan National Institute of Science and Technology, Ulsan 44919, Korea. ⁶Department of Biology, MIT, Cambridge, Massachusetts 02139, USA. ⁷These authors contributed equally to this work. ⁸Present addresses:Department of Hematology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, USA (M.-J.H.); Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas 78712, USA (J.Z.).
⁹Correspondence should be addressed to K.-S.K.

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.

논문정보

형식Research article
게재일2017년 04월 (BRIC 등록일 2017-04-24)
연구진국내+국외 연구진
분야 생명과학 > 신경생물학

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