title: Core Pluripotency Factors Directly Regulate Metabolism in Embryonic Stem Cell to Maintain Pluripotency.
abstract: Pluripotent stem cells (PSCs) have distinct metabolic properties that support their metabolic and energetic needs and affect their stemness. In particular, high glycolysis is critical for the generation and maintenance of PSCs. However, it is unknown how PSCs maintain and acquire this metabolic signature. In this study, we found that core pluripotency factors regulate glycolysis directly by controlling the expression of glycolytic enzymes. Specifically, Oct4 directly governs Hk2 and Pkm2, which are important glycolytic enzymes that determine the rate of glycolytic flux. The overexpression of Hk2 and Pkm2 sustains high levels of glycolysis during embryonic stem cell (ESC) differentiation. Moreover, the maintenance of high glycolysis levels by Hk2 and Pkm2 overexpression hampers differentiation and preserves the pluripotency of ESCs in the absence of leukemia inhibitory factor. Overall, our study identifies a direct molecular connection between core pluripotency factors and ESC metabolic signatures and demonstrates the significance of metabolism in cell fate determination.
authors.affiliation: Department of Biomedical Sciences, National Creative Research Center for Epigenome Reprogramming Network, Ischemic/Hypoxic Disease Institute.
authors.forename: Hyunsoo
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, National Creative Research Center for Epigenome Reprogramming Network, Ischemic/Hypoxic Disease Institute.|Division of Cancer Biology, Research Institute & Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea.
authors.forename: Hyonchol
authors.initials: H
authors.lastname: Jang
authors.affiliation: Department of Biomedical Sciences, National Creative Research Center for Epigenome Reprogramming Network, Ischemic/Hypoxic Disease Institute.
authors.forename: Tae Wan
authors.initials: TW
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, National Creative Research Center for Epigenome Reprogramming Network, Ischemic/Hypoxic Disease Institute.
authors.forename: Byung-Hee
authors.initials: BH
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, National Creative Research Center for Epigenome Reprogramming Network, Ischemic/Hypoxic Disease Institute.|Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.affiliation: Department of Biomedical Sciences, National Creative Research Center for Epigenome Reprogramming Network, Ischemic/Hypoxic Disease Institute.|Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
authors.affiliation: Department of Biomedical Sciences, National Creative Research Center for Epigenome Reprogramming Network, Ischemic/Hypoxic Disease Institute.
authors.forename: Jinmi
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Biomedical Sciences, National Creative Research Center for Epigenome Reprogramming Network, Ischemic/Hypoxic Disease Institute.
authors.forename: Jihoon
authors.initials: J
authors.lastname: Shin
authors.affiliation: College of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Cho
authors.affiliation: Department of Biomedical Sciences, National Creative Research Center for Epigenome Reprogramming Network, Ischemic/Hypoxic Disease Institute.|Department of Molecular Medicine & Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hong-Duk
authors.initials: HD
authors.lastname: Youn
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000502:physiology; D053595:Embryonic Stem Cells / Q000378:metabolism*; D006019:Glycolysis / Q000502:physiology*; D006593:Hexokinase / Q000096:biosynthesis*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis*; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D013963:Thyroid Hormones / Q000096:biosynthesis*; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D006593:Hexokinase; D008565:Membrane Proteins; D050814:Octamer Transcription Factor-3; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C494173:POU5F1 protein, human; C000598049:hexokinase 2, mouse
keywords: Core pluripotency factors; Embryonic stem cells; Glycolysis; Hexokinase 2; Metabolism; Oct4; Pyruvate kinase M2