Reconstructing human brown fat developmental trajectory in vitro.

Brown adipocytes (BAs) represent a specialized cell type that is able to uncouple nutrient catabolism from ATP generation to dissipate energy as heat. In humans, the brown fat tissue is composed of discrete depots found throughout the neck and trunk region. BAs originate from a precursor common to skeletal muscle, but their developmental trajectory remains poorly understood. Here, we used single-cell RNA sequencing to characterize the development of interscapular brown fat in mice. Our analysis identified a transient stage of BA differentiation characterized by the expression of the transcription factor GATA6. We show that recapitulating the sequence of signaling cues identified in mice can lead to efficient differentiation of BAs in vitro from human pluripotent stem cells. These precursors can in turn be efficiently converted into functional BAs that can respond to signals mimicking adrenergic stimuli by increasing their metabolism, resulting in heat production. Copyright © 2023 Elsevier Inc. All rights reserved.

Citation

Jyoti Rao, Yannis Djeffal, Jerome Chal, Fabio Marchianò, Chih-Hao Wang, Ziad Al Tanoury, Svetlana Gapon, Alicia Mayeuf-Louchart, Ian Glass, Elizabeth M Sefton, Bianca Habermann, Gabrielle Kardon, Fiona M Watt, Yu-Hua Tseng, Olivier Pourquié. Reconstructing human brown fat developmental trajectory in vitro. Developmental cell. 2023 Aug 24

PMID: 37647896

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