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Published on: March 28, 2013
Generation of Functional Brown Adipocytes from Human Pluripotent Stem Cells via Progression through a Paraxial
Liang Zhang1, John Avery1, Amelia Yin1
1Center for Molecular Medicine, University of Georgia, 325 Riverbend Road, Athens, GA 30605, USA; Department of Biochemistry and Molecular Biology, University of Georgia, 325 Riverbend Road, Athens, GA 30605, USA.
Abstract:
Brown adipocytes (BAs) are a potential cell source for the treatment of metabolic disease, including type 2 diabetes. In this report, human pluripotent stem cells (hPSCs) are subject to directed differentiation through a paraxial mesoderm progenitor state that generates BAs at high efficiency. Molecular analysis identifies potential regulatory networks for BA development, giving insight into development along this lineage. hPSC-derived BAs undergo elevated rates of glycolysis, uncoupled respiration, and lipolysis that are responsive to changes in cyclic AMP (cAMP)-dependent signaling, consistent with metabolic activity in BA tissue depots. Transplanted human BAs engraft into the inter-scapular region of recipient mice and exhibit thermogenic activity. Recipient animals have elevated metabolic activity, respiratory exchange ratios, and whole-body energy expenditure. Finally, transplanted BAs reduce circulating glucose levels in hyperglycemic animals. These data provide a roadmap for brown adipocyte development and indicate that BAs generated from hPSCs have potential as a tool for therapeutic development.
