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. 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.
Bibliographical noteFunding Information:
This work was supported by NIH grants RO1DK62292 and RO1DK102455 (to J.G.G.), and 1R01GM109215 (to R.P.-R.), and by equipment funds from the Office of the Vice President for Research, Wayne State University . We thank Jian Wang, Doug Ruden, and Todd Leff for thoughtful reviews.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology