Control of murine brown adipocyte development by GATA6

Brown adipose tissue (BAT) is a thermogenic organ that protects animals against hypothermia and obesity. BAT derives from the multipotent paraxial mesoderm; however, the identity of embryonic brown fat progenitor cells and regulators of adipogenic commitment are unclear. Here, we performed single-ce...

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Bibliographic Details
Published in:	Developmental cell Vol. 58; no. 21; pp. 2195 - 2205.e5
Main Authors:	Jun, Seoyoung, Angueira, Anthony R, Fein, Ethan C, Tan, Josephine M E, Weller, Angela H, Cheng, Lan, Batmanov, Kirill, Ishibashi, Jeff, Sakers, Alexander P, Stine, Rachel R, Seale, Patrick
Format:	Journal Article
Language:	English
Published:	United States 06-11-2023
Subjects:	Adipocytes, Brown - metabolism Adipogenesis Adipose Tissue, Brown - metabolism Animals Dipeptidyl Peptidase 4 - metabolism Mice Obesity - metabolism Thermogenesis - genetics DPP4 brown adipogenesis brown adipocyte GATA6 UCP1 adipose tissue EBF2 progenitor brown adipocyte development
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Summary:	Brown adipose tissue (BAT) is a thermogenic organ that protects animals against hypothermia and obesity. BAT derives from the multipotent paraxial mesoderm; however, the identity of embryonic brown fat progenitor cells and regulators of adipogenic commitment are unclear. Here, we performed single-cell gene expression analyses of mesenchymal cells during mouse embryogenesis with a focus on BAT development. We identified cell populations associated with the development of BAT, including Dpp4+ cells that emerge at the onset of adipogenic commitment. Immunostaining and lineage-tracing studies show that Dpp4+ cells constitute the BAT fascia and contribute minorly as adipocyte progenitors. Additionally, we identified the transcription factor GATA6 as a marker of brown adipogenic progenitor cells. Deletion of Gata6 in the brown fat lineage resulted in a striking loss of BAT. Together, these results identify progenitor and transitional cells in the brown adipose lineage and define a crucial role for GATA6 in BAT development.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 S.J., A.R.A., E.C.F. and P.S. were responsible for conceptualization, data analysis and writing the manuscript. S.J. and A.R.A. conducted the majority of the experiments. E.C.F. and A.R.A carried out the bioinformatics analyses of scRNAseq datasets. L.C. processed tissue sections for histology and performed immunostaining. J.M.E.T. performed imaging analysis and assisted with experiments. A.H.W. and K.B. performed ChIP analyses. R.R.S. assisted with experiments and writing of the manuscript. A.S. and J.I. developed cell isolation and embryo cell sorting procedures and assisted in preparing cells for sequencing. Author Contributions
ISSN:	1534-5807 1878-1551 1878-1551
DOI:	10.1016/j.devcel.2023.08.003