Resolving the Heterogeneity of Adipose Stromal and Progenitor Cells (ASPCs)

White adipose tissue harbours a highly diverse population of adipose stromal and progenitor cells (ASPCs), including fibroblast-like cells and preadipocytes, which play central roles in tissue development, extracellular matrix organization, inflammation, and metabolic regulation. While recent single-cell and spatial transcriptomic studies have revealed previously unrecognized ASPC subpopulations - some of which are closely associated with the vasculature - their spatial organization, functional properties, and contribution to metabolic disease remain poorly understood.

This project aims to systematically dissect ASPC heterogeneity and function by combining spatially resolved human tissue data with advanced experimental models. We focus in particular on vasculature-associated fibroblast subtypes and their interactions with endothelial cells. To this end, we establish human 3D co-culture systems that recapitulate key aspects of the adipose tissue microenvironment and allow direct investigation of fibroblast–endothelial crosstalk and angiogenic processes. These models are complemented by CRISPR/Cas9-based genetic perturbation approaches targeting candidate regulators identified from spatial and single-cell analyses.

Findings from the in vitro systems are validated using primary human adipose tissue–derived cells and in vivo transplantation models, enabling functional assessment of ASPC subpopulations in a physiological context. By linking defined cellular subtypes to specific functional roles in angiogenesis and tissue remodeling, this work seeks to clarify how disruptions in ASPC composition and behavior contribute to adipose tissue dysfunction in metabolic disease, and to identify novel cellular and molecular targets for therapeutic intervention.