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

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