Metabolic Regulation by Core Pluripotency Factors for Maintaining Embryonic Stem Cell 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 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