ScRNAseq - Beige and white subcutaneous adipocytes arise from a common progenitor population in humans

ABSTRACT: The thermogenic capacity of adipose tissue varies among individuals and declines with age, obesity, and insulin resistance. We hypothesized that this variability may originate from intrinsic differences in adipose progenitor cell populations and in their thermogenic potential. To test this, we performed parallel white and beige adipogenic differentiation using primary subcutaneous adipose progenitors isolated from 6 unrelated healthy subjects. We find that PPARγ agonist treatment activates subject-specific thermogenic programs, involving both UCP1-dependent and non-canonical thermogenic pathways. Single-cell transcriptomic profiling of the progenitor cells from the six subjects reveals broad transcriptional heterogeneity, manifested by differential expression of extracellular matrix, cell adhesion, and cytoskeletal genes. Single-cell mapping during adipogenic commitment resolves a continuum of transcriptional states that largely overlap between white and beige conditions, with trajectory analyses tracing back to a common progenitor pool. However, we find that beige induction results in a higher proportion of structural Wnt-regulated adipose tissue resident (SWAT) cells, with a distinct expression profile of extracellular matrix genes, suggesting that early fate-specific remodelling of the extracellular environment may potentiate functional plasticity in mature cells. Together, these findings support a model in which individual differences in thermogenic capacity primarily arise from plasticity of mature adipocytes, driven by genetic, environmental and epigenetic factors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE301263 | GEO | 2026/09/21

REPOSITORIES: GEO