Heterogeneity and Clinical Relevance of Human Adipose Stromal and Progenitor Cells.

Adipose stromal and progenitor cells (ASPCs) represent the largest cell population in human white adipose tissue (WAT). Despite their abundance, ASPC heterogeneity remains less well characterized compared to adipocytes or immune cells. Recent single-cell transcriptome studies provide unprecedented resolution of ASPC diversity and function. This review summarizes state-of-the-art approaches, including high-resolution single-cell methods, classical lineage and functional assays, to define ASPC populations. By systematically comparing recent datasets, we identify evidence for at least eight distinct ASPC-subtypes, which demonstrate specific marker genes and putative functional diversity. Along the adipogenic trajectory, these include uncommitted multipotent progenitors, intermediate and committed preadipocytes, and premature adipocytes. Additional populations comprise specialized anti-adipogenic, profibrotic, inflammatory, and fibroblast-like ASPCs. Other cell types are not consistently detected across studies, reflecting both biological and methodological variability, and the need for further validation studies. Better understanding of ASPC heterogeneity may improve the clinical assessment of metabolic disorders and support their treatment. We further discuss subtype-specific (dys)functions linked to fibrosis, inflammation and impaired adipogenesis and describe their increased abundance in metabolic disease. Together, this review integrates current knowledge on ASPC heterogeneity and highlights its clinical relevance, aiming to provide a unified framework for future studies on WAT remodeling and metabolic dysfunction.