Reconstructing human brown fat developmental trajectory in vitro.

Autor:	Rao J; Department of Pathology, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, 60 Fenwood Road, Boston, MA 02115, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA., Djeffal Y; Department of Pathology, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, 60 Fenwood Road, Boston, MA 02115, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA., Chal J; Department of Pathology, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, 60 Fenwood Road, Boston, MA 02115, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA., Marchianò F; Aix-Marseille University, CNRS, IBDM, The Turing Center for Living Systems, 13009 Marseille, France., Wang CH; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA., Al Tanoury Z; Department of Pathology, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, 60 Fenwood Road, Boston, MA 02115, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA., Gapon S; Department of Pathology, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, 60 Fenwood Road, Boston, MA 02115, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA., Mayeuf-Louchart A; Univ. Lille, INSERM, CHU Lille, Institut Pasteur de Lille, 59000 Lille, France., Glass I; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA., Sefton EM; Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA., Habermann B; Aix-Marseille University, CNRS, IBDM, The Turing Center for Living Systems, 13009 Marseille, France., Kardon G; Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA., Watt FM; King's College London Centre for Stem Cells and Regenerative Medicine, Great Maze Pond, London SE1 9RT, UK., Tseng YH; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA., Pourquié O; Department of Pathology, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, 60 Fenwood Road, Boston, MA 02115, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. Electronic address: pourquie@genetics.med.harvard.edu.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2023 Nov 06; Vol. 58 (21), pp. 2359-2375.e8. Date of Electronic Publication: 2023 Aug 29.
DOI:	10.1016/j.devcel.2023.08.001
Abstrakt:	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. Competing Interests: Declaration of interests J.R. and O.P. have filed a patent related to this work. (Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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