Deconstructing cold-induced brown adipocyte neogenesis in mice
- Wayne State University, United States
Abstract
Cold exposure triggers neogenesis in classic interscapular brown adipose tissue (iBAT) that involves activation of b1-adrenergic receptors, proliferation of PDGFRA+ adipose tissue stromal cells (ASCs), and recruitment of immune cells whose phenotypes are presently unknown. Single-cell RNA-sequencing (scRNA-seq) in mice identified three ASC subpopulations that occupied distinct tissue locations. Of these, interstitial ASC1 were found to be direct precursors of new brown adipocytes (BAs). Surprisingly, knockout of b1-adrenergic receptors in ASCs did not prevent cold-induced neogenesis, whereas pharmacological activation of the b3-adrenergic receptor on BAs was sufficient, suggesting that signals derived from mature BAs indirectly trigger ASC proliferation and differentiation. In this regard, cold exposure induced the delayed appearance of multiple macrophage and dendritic cell populations whose recruitment strongly correlated with the onset and magnitude of neogenesis across diverse experimental conditions. High resolution immunofluorescence and single molecule fluorescence in situ hybridization demonstrated that cold-induced neogenesis involves dynamic interactions between ASC1 and recruited immune cells that occur on the micrometer scale in distinct tissue regions. Our results indicate that neogenesis is not a reflexive response of progenitors to b-adrenergic signaling, but rather is a complex adaptive response to elevated metabolic demand within brown adipocytes.
Data availability
Sequencing data from this study has been deposited in the Gene Expression Omnibus (GEO) under the series accession number GSE207707. Scripts for data processing will be made available through GitHub (https://github.com/RBBurl1227).
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Deconstructing cold-induced brown adipocyte neogenesis in miceNCBI Gene Expression Omnibus, GSE207707.
Article and author information
Author details
Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK062292)
- James G Granneman
National Institute of Diabetes and Digestive and Kidney Diseases (F31-DK116536)
- Rayanne B Burl
Funding sources were not involved in the study design, collection and/or interpretation of data, nor the decision to submit this work for publication.
Ethics
Animal experimentation: All animal protocols were approved and conducted in accordance with the Institutional Animal Care and Use Committee at Wayne State University (#16-03-055 and #19-03-1024).
Copyright
© 2022, Burl et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Deconstructing cold-induced brown adipocyte neogenesis in mice
eLife 11:e80167.
https://doi.org/10.7554/eLife.80167
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