Abstract 4360: Distinct energy metabolism in human pluripotent stem cells and differentiated cells regulated by UCP2

Abstract

Abstract It has been assumed, based largely on morphologic evidence, that human pluripotent stem cells (hPSCs) contain underdeveloped, bioenergetically inactive mitochondria. In contrast, differentiated cells harbor a fused, branching mitochondrial network, with oxidative phosphorylation (OXPHOS) as the main energy source. A role for mitochondria in hPSC bioenergetics therefore remains uncertain. Here we show that hPSCs have functional respiratory complexes that consume O2 at maximal capacity. Despite this, ATP generation in hPSCs is mainly by glycolysis. To help maintain hPSC mitochondrial membrane potential, cell proliferation, and viability, glycolytic ATP is hydrolyzed by the mitochondrial F1F0ATP synthase. Uncoupling protein 2 (UCP2) regulates this unique pattern of hPSC energy metabolism while suppressing reactive oxygen species. Upon differentiation, UCP2 is repressed and cells shift from glycolysis and fatty acid oxidation to glucose oxidation dependency. Ectopic UCP2 expression during differentiation blocks this metabolic transition and blocks proper embryoid body formation. Combined, our data show that hPSC have distinct bioenergetics regulated by UCP2 and repression of UCP2 is required for metabolic reprogramming along differentiation Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4360. doi:10.1158/1538-7445.AM2011-4360