生物
胚胎干细胞
诱导多能干细胞
细胞生物学
糖酵解
巴基斯坦卢比
干细胞
细胞分化
丙酮酸激酶
生物化学
新陈代谢
基因
作者
Hyunsoo Kim,Hyonchol Jang,Tae Wan Kim,Byung Hee Kang,Sang Eun Lee,Yoon Kyung Jeon,Doo Hyun Chung,Jinmi Choi,Jihoon Shin,Eun Jung Cho,Hong Duk Youn
出处
期刊:Stem Cells
[Wiley]
日期:2015-06-23
卷期号:33 (9): 2699-2711
被引量:92
摘要
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.
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