Deconstructing Adipogenesis Induced by β3-Adrenergic Receptor Activation with Single-Cell Expression Profiling

Recruitment of brown/beige adipocytes (BAs) in white adipose tissue (WAT) involves proliferation and differentiation of adipocyte stem cells (ASCs) in concert with close interactions with resident immune cells. To deconvolve stromal cell heterogeneity in a comprehensive and unbiased fashion, we performed single-cell RNA sequencing (scRNA-seq) of >33,000 stromal/vascular cells from epididymal WAT (eWAT) and inguinal WAT (iWAT) under control conditions and during β3-adrenergic receptor (ADRB3) activation. scRNA-seq identified distinct ASC subpopulations in eWAT and iWAT that appeared to be differentially poised to enter the adipogenic pathway. ADRB3 activation triggered the dramatic appearance of proliferating ASCs in eWAT, whose differentiation into BAs could be inferred from a single time point. scRNA-seq identified various immune cell types in eWAT, including a proliferating macrophage subpopulation that occupies adipogenic niches. These results demonstrate the power of scRNA-seq to deconstruct adipogenic niches and suggest novel functional interactions among resident stromal cell subpopulations. [Display omitted] •Transcriptomes of >33,000 single adipose tissue stromal cells are provided•scRNA-seq reveals heterogeneity of adipocyte progenitors and immune cells•scRNA-seq identifies adipogenic niches and maps differentiation trajectories Burl et al. employ single-cell RNA sequencing (scRNA-seq) of mouse adipose tissue to identify distinct subpopulations of adipocyte progenitors and immune cells. In a model of in vivo brown adipogenesis, scRNA-seq data are used to deconstruct adipogenic niches, map differentiation trajectories, and suggest novel functional interactions among resident stromal cell subpopulations.