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Updated: Feb 19, 2026

Differentiation and Imaging of Brown Adipocytes from the Stromal Vascular Fraction of Interscapular Adipose Tissue from Newborn Mice
Published on: February 3, 2023
TGFβ-activated PDHB promotes mitochondrial pyruvate metabolism and contributes to human endoderm differentiation via
Liming Meng1, Jing Lv1,2, Ying Yi1
1Department of Biological Repositories, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Abstract:
Cell fate determination is closely linked to metabolic state, yet how metabolic remodeling influences human pluripotent stem cells differentiation into three germ layers remains incompletely understood. Here, we reveal that definitive endoderm differentiation from human pluripotent stem cells requires a TGFβ-driven metabolic switch characterized by reduced lactate production and enhanced TCA cycle activity and oxidative phosphorylation, mediated by PDHB. Disruption of glucose utilization or pyruvate entry into the TCA cycle markedly impairs endoderm differentiation, whereas inhibition of lactate production enhances differentiation efficiency. Mechanistically, blockade of glucose metabolism or the TCA cycle reduces intracellular ATP levels, compromising the activity of BAF complex, an ATP-dependent chromatin remodeling complex centered on BRG1. This complex promotes chromatin accessibility and activates endodermal gene programs during differentiation. Together, these findings highlight metabolic reprogramming as a key regulator of human endoderm fate through ATP-dependent control of chromatin remodeling.
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