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.组织巨噬细胞（Tissue macrophages）是一类异质性细胞群，定植于多样的亚组织微龛中，其组织特异性功能由所处的亚组织微环境决定。本研究针对脂肪组织巨噬细胞（adipose tissue macrophages, ATM）的亚组织定位与功能特化情况解析了其异质性。我们鉴定出3种定植于不同亚组织微龛的ATM亚群，各具有独特的更新特性、表型与功能：分别为CD209b–LYVE1–CD16.2+ 实质区ATM、CD209b–LYVE1+CD16.2– 被膜区ATM，以及CD209b+LYVE1+CD16.2– 间隔区ATM；其中间隔区ATM特异性定位于白色脂肪组织间隔中，并与CD26+ 脂肪干细胞（adipocyte stem cells, ASC）直接接触。在高脂饮食（high-fat diet, HFD）模型中，间隔区ATM的耗竭或其转化生长因子β1（transforming growth factor β1, TGFβ1）表达缺陷，会改变脂肪干细胞的成脂潜能，促进米色化过程，从而抑制饮食诱导的肥胖。本研究结果揭示了一类解剖学定位明确的巨噬细胞群的调控作用，及其与脂肪干细胞的互作可调控脂肪干细胞的命运，最终影响脂肪组织的扩张。