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Metabolic Regulation by Core Pluripotency Factors for Maintaining Embryonic Stem Cell Pluripotency
배아줄기세포의 전분화성 유지를 위한 Core Pluripotency Factor의 대사조절

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Authors
김현수
Advisor
윤홍덕
Major
의과대학 의과학과
Issue Date
2016-08
Publisher
서울대학교 대학원
Keywords
줄기세포
Description
학위논문 (박사)-- 서울대학교 대학원 : 의과학과, 2016. 8. 윤홍덕.
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 LIF. 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.

* This work is published in Stem Cells
published online September, 2015 DOI: 10.1002/stem.2073


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Keywords: embryonic stem cells, core pluripotency factors, Oct4, metabolism, glycolysis, hexokinase 2 (Hk2), pyruvate kinase M2 (Pkm2), pluripotency, differentiation
Student number: 2009-30601
Language
English
URI
https://hdl.handle.net/10371/122326
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biomedical Sciences (대학원 의과학과)Theses (Ph.D. / Sc.D._의과학과)
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