4.8 Article

Brown adipose tissue monocytes support tissue expansion

期刊

NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -

出版社

NATURE PORTFOLIO
DOI: 10.1038/s41467-021-25616-1

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资金

  1. Conseil Regional
  2. Conseil Departemental
  3. IBISA
  4. French government, through the UCAJedi Investments [ANR-15-IDEX-01]
  5. Agence Nationale de la Recherche [ANR-18-CE14-0025, ANR-20CE14-0006-02, ANR-17-CE14-0017-01, ANR-19-ECVD-0005-01]
  6. Government of Russian Federation [08-08]
  7. Center National de la Recherche Scientifique (CNRS)
  8. ANR
  9. European Union: EGID [ANR-10-LABX-46]
  10. National Institutes of Health (NIH) [HL138163]
  11. Institut National de la Sante et de la Recherche Medicale (INSERM)
  12. Fondation de France [00066474]
  13. European Research Council (ERC) [ERC2016COG724838]
  14. Agence Nationale de la Recherche (ANR) [ANR-18-CE14-0025, ANR-19-ECVD-0005, ANR-17-CE14-0017] Funding Source: Agence Nationale de la Recherche (ANR)

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The study revealed a large diversity in monocyte and macrophage populations in brown adipose tissue, with monocytes playing a crucial role in tissue expansion and requiring constant replenishment. This highlights the importance of monocyte recruitment for tissue remodeling and expansion in BAT.
Monocytes are part of the mononuclear phagocytic system. Monocytes play a central role during inflammatory conditions and a better understanding of their dynamics might open therapeutic opportunities. In the present study, we focused on the characterization and impact of monocytes on brown adipose tissue (BAT) functions during tissue remodeling. Single-cell RNA sequencing analysis of BAT immune cells uncovered a large diversity in monocyte and macrophage populations. Fate-mapping experiments demonstrated that the BAT macrophage pool requires constant replenishment from monocytes. Using a genetic model of BAT expansion, we found that brown fat monocyte numbers were selectively increased in this scenario. This observation was confirmed using a CCR2-binding radiotracer and positron emission tomography. Importantly, in line with their tissue recruitment, blood monocyte counts were decreased while bone marrow hematopoiesis was not affected. Monocyte depletion prevented brown adipose tissue expansion and altered its architecture. Podoplanin engagement is strictly required for BAT expansion. Together, these data redefine the diversity of immune cells in the BAT and emphasize the role of monocyte recruitment for tissue remodeling. Adipose tissue is composed of a number of adipocytes and a number of other cells including immune cells. Here the authors use single-cell sequencing of murine brown adipose tissue immune cells and describe multiple macrophage and monocyte subsets and show that monocytes contribute to brown adipose tissue expansion.

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