Thermogenic capacity in adipose tissue varies among individuals and declines with age, obesity, and insulin resistance. To investigate the cellular basis of this variability, we performed parallel white and beige adipogenic differentiation using subcutaneous adipose progenitors from six healthy subjects. Beige adipogenesis elicits subject-specific, UCP1-dependent, and non-canonical thermogenic programs. Single-cell transcriptomics reveals varied proportions of progenitor populations, defined by differential expression of extracellular matrix, cell adhesion, and cytoskeletal genes. Mapping adipogenic commitment uncovers a continuum of transcriptional states largely shared between white and beige differentiation. Within this continuum, we identify ICAM1-positive committed progenitors contributing to both white and beige phenotypes. Beige induction increases the proportion of structural adipose tissue-resident cells with distinct extracellular matrix signatures, suggesting that early microenvironmental remodeling primes plasticity in mature cells. These results support a model in which diverse adipocyte fates arise from plastic progenitors, with individual differences in thermogenic adaptation driven by genetic, environmental, and epigenetic factors.
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Pickering et al. (2026) studied this question.
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