Defining the Vascular Niche of Human Adipose Tissue Across Metabolic Conditions

Adipose tissue physiology and homeostasis depends on a healthy vascular network. Vascular malfunction is a hallmark of obesity, and vascular endothelial dysfunction, in particular, precipitates metabolic diseases, including obesity and type two diabetes. Although single-cell transcriptomics approaches have defined atlases of human white adipose tissue (WAT) cells, the associated adipose vascular cells remain relatively undefined. Specifically, there is limited information on their heterogeneity and function, and roles in metabolic disease. To address this gap, we created a single-cell transcriptome atlas of human subcutaneous adipose tissue (SAT), comprising nearly 70,000 vascular cells from 65 individuals. We identified eight adipose endothelial cell (AdEC) populations, comprising seven canonical subtypes and a previously undescribed, heterogeneous population we named sub-AdECs. Sub-AdECs exhibit gene signatures characteristic of multiple cell types, including mesenchymal, adipocytic, and immune cells, suggesting they possess diverse properties and identities. Furthermore, we compare the transcriptomes of vascular cells from individuals living with or without obesity and type two diabetes and find metabolic disease-associated inflammatory and fibrotic transcriptomic patterns. The atlas and accompanying analyses establish a solid foundation for future investigations into the biology of vascular cells within WAT and their contributions to metabolic diseases.