eLife-Identification of functionally distinct fibro-inflammatory and adipogenic stromal subpopulations in visceral adipose tissue of adult mice.pdf

White adipose tissue (WAT) remodeling is dictated by coordinated interactions
between adipocytes and resident stromal-vascular cells; however, the functional heterogeneity of
adipose stromal cells has remained unresolved. We combined single-cell RNA-sequencing and
FACS to identify and isolate functionally distinct subpopulations of PDGFRb+ stromal cells within
visceral WAT of adult mice. LY6C- CD9- PDGFRb+ cells represent highly adipogenic visceral
adipocyte precursor cells (‘APCs’), whereas LY6C+ PDGFRb+ cells represent fibro-inflammatory
progenitors (‘FIPs’). FIPs lack adipogenic capacity, display pro-fibrogenic/pro-inflammatory
phenotypes, and can exert an anti-adipogenic effect on APCs. The pro-inflammatory phenotype of
PDGFRb+ cells is regulated, at least in part, by NR4A nuclear receptors. These data highlight the
functional heterogeneity of visceral WAT perivascular cells, and provide insight into potential cell-
cell interactions impacting adipogenesis and inflammation. These improved strategies to isolate
FIPs and APCs from visceral WAT will facilitate the study of physiological WAT remodeling and
mechanisms leading to metabolic dysfunction.