Septal LYVE1+ macrophages control adipocyte stem cell adipogenic potential

Tissue macrophages are a heterogeneous cell population residing in diverse subtissular niches dictating their tissue-specific functions. Here, we assessed the heterogeneity of adipose tissue macrophages (ATM) in regard to their subtissular localization and functional specializations. We identified 3 ATM populations residing in  subtissular niche with distinct turnover, phenotypes and functions: CD209b–LYVE1–CD16.2+ parenchymal ATM, CD209b–LYVE1+CD16.2– capsular ATM and CD209b+LYVE1+CD16.2– septal ATM, the latter specifically localized in white adipose tissue septum in contact with CD26+ adipocyte stem cells (ASC). Septal ATM depletion or their deficiency in transforming growth factor β1 (TGFβ1) expression in the context of HFD changed ASC adipogenic potential promoting a beiging process, thus preventing diet-induced obesity. Our findings highlight the role played by a discrete anatomically-defined macrophage population and their crosstalk with ASC, controlling their fate and ultimately tissue expansion.