Distinct properties of adipose stem cell subpopulations determine fat depot-specific characteristics

Abstract

In mammals, white adipose tissues are largely divided into visceral epididymal adipose tissue (EAT) and subcutaneous inguinal adipose tissue (IAT) with distinct metabolic properties. Although emerging evidence suggests that subpopulations of adipose stem cells (ASCs) would be important to explain fat depot differences, ASCs of two fat depots have not been comparatively investigated. Here, we characterized heterogeneous ASCs and examined the effects of intrinsic and tissue micro-environmental factors on distinct ASC features. We demonstrated that ASC subpopulations in EAT and IAT exhibited different molecular features with three adipogenic stages. ASC transplantation experiments revealed that intrinsic ASC features primarily determined their adipogenic potential. Upon obesogenic stimuli, EAT-specific SDC1⁺ ASCs promoted fibrotic remodeling, whereas IAT-specific CXCL14⁺ ASCs suppressed macrophage infiltration. Moreover, IAT-specific BST2^high ASCs exhibited a high potential to become beige adipocytes. Collectively, our data broaden the understanding of ASCs with new insights into the origin of white fat depot differences.

Keywords: adipogenesis; adipose stem cells; adipose tissue remodeling; beige adipocytes; fat depots; fibrosis; inflammation; lymph nodes; obesity; single-cell RNA-seq.