Septal LYVE1+ macrophages control adipocyte stem cell adipogenic potential

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.