Septal LYVE1 <sup>+</sup> macrophages control adipocyte stem cell adipogenic potential

Tissue macrophages reside in anatomically distinct subtissular niches that shape their identity and function. In white adipose tissue (WAT), we identified three macrophage populations with distinct localization, turnover, and phenotypes. Septal adipose tissue macrophages (sATMs), marked by CD209b and lymphatic vessel endothelial hyaluronan receptor 1, were long-lived and positioned in close proximity to adipocyte stem cells (ASCs) within the WAT septum. Within this shared niche, sATMs instructed the differentiation of ASCs into white adipocytes through transforming growth factor-β1 (TGFβ1). Depletion of sATMs, or the selective loss of TGFβ1 within tissue-resident macrophages, redirected ASC fate toward thermogenic adipocytes, enhancing WAT beiging and protecting against diet-induced obesity. These findings highlight the role of a discrete, anatomically defined macrophage population that governs ASC fate and orchestrates adipose tissue expansion.

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Publication Details

Journal
Science
Published
2025-08-28
DOI
https://doi.org/10.1126/science.adg1128
Citations
16
Primary Topic
Adipose Tissue and Metabolism
Type
article
Field-Weighted Citation Impact
18.63
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article

Septal LYVE1 + macrophages control adipocyte stem cell adipogenic potential

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article

Septal LYVE1 + macrophages control adipocyte stem cell adipogenic potential

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article en
16 citations

Abstract

Tissue macrophages reside in anatomically distinct subtissular niches that shape their identity and function. In white adipose tissue (WAT), we identified three macrophage populations with distinct localization, turnover, and phenotypes. Septal adipose tissue macrophages (sATMs), marked by CD209b and lymphatic vessel endothelial hyaluronan receptor 1, were long-lived and positioned in close proximity to adipocyte stem cells (ASCs) within the WAT septum. Within this shared niche, sATMs instructed the differentiation of ASCs into white adipocytes through transforming growth factor-β1 (TGFβ1). Depletion of sATMs, or the selective loss of TGFβ1 within tissue-resident macrophages, redirected ASC fate toward thermogenic adipocytes, enhancing WAT beiging and protecting against diet-induced obesity. These findings highlight the role of a discrete, anatomically defined macrophage population that governs ASC fate and orchestrates adipose tissue expansion.

ScienceVol. 389(6763)
Agency for Science, Technology and Research (SG), University of Bonn (DE), Central South University (CN), National University of Singapore (SG), Shanghai Jiao Tong University (CN), Université Paris Cité (FR), Aix-Marseille Université (FR), Kyoto University (JP), Renji Hospital (CN), Singapore Immunology Network (SG), Institut Gustave Roussy (FR), Institut Necker Enfants Malades (FR), Shanghai Ninth People's Hospital (CN), SingHealth Duke-NUS Academic Medical Centre (SG), Centre d’Immunologie de Marseille-Luminy (FR), Xiangya Hospital Central South University (CN), A*STAR Graduate Academy (SG), Weizmann Institute of Science (IL), Institute of Molecular and Cell Biology (SG)
Openalex Percentile: Top 0%
Adipose Tissue and Metabolism
18.63
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