Surface protein profiling reveals depot-specific features of subcutaneous and visceral adipose progenitor cells.

White adipose tissue is organized into anatomically and functionally distinct depots, yet the mechanisms by which intrinsic differences between subcutaneous and visceral adipose progenitor cells (APCs) contribute to depot-specific inflammatory and remodeling properties remain unresolved. Here, by directly comparing APCs isolated from subcutaneous and visceral fat, we identify distinct surface protein programs underlying their divergent functional properties. Subcutaneous APCs exhibited elevated expression of galectin-9, CD44, and CD63, defining functional programs governing immune modulation, adipogenesis, and exosome-mediated stress adaptation. Functional assays revealed that galectin-9 promotes an anti-inflammatory phenotype, CD44 quantitatively modulates adipogenic differentiation, and CD63 enhances exosome release and confers resistance to iron-induced cellular stress. Notably, several depot-specific features were not evident at the transcriptomic level, underscoring the importance of surface protein-level regulation. Together, our findings demonstrate that APC surface protein signatures distinguish subcutaneous from visceral fat, establishing a mechanistic link between depot identity, tissue remodeling, and metabolic disease susceptibility.