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

Cell Metab. 2018 Aug 7;28(2):300-309.e4. doi: 10.1016/j.cmet.2018.05.025. Epub 2018 Jun 21.


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.

Keywords: RNA-seq; adipocyte stem cell; adipogenesis; brown adipocyte; browning; differentiation trajectory; macrophage; recuitment; stromal cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis*
  • Adipose Tissue, White / cytology
  • Adipose Tissue, White / metabolism*
  • Animals
  • Cell Proliferation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Adrenergic, beta-3 / metabolism*
  • Sequence Analysis, RNA / methods
  • Single-Cell Analysis*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Stromal Cells / cytology
  • Stromal Cells / metabolism*
  • Transcriptome*


  • Adrb3 protein, mouse
  • Receptors, Adrenergic, beta-3