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

Abstract

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 PDGFRβ+ stromal cells within visceral WAT of adult mice. LY6C- CD9- PDGFRβ+ cells represent highly adipogenic visceral adipocyte precursor cells (‘APCs’), whereas LY6C+ PDGFRβ+ 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 PDGFRβ+ 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.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

Leptin in the regulation of the immunometabolism of adipose tissue-macrophages

“…WAT inflammation is associated with activation of immune cells, the presence of enlarged, unhealthy adipocytes and the accumulation of collagen fibers in the tissue. A recent study identified a new inflammatory subpopulation of cells in the adipose tissue of mice . A combined technique of single‐cell RNA‐sequencing and FACS isolation was utilized to identify the so called fibro‐inflammatory progenitors (FIPs) cells residing around the blood vessels in the visceral adipose tissue of mice .…”

“…A recent study identified a new inflammatory subpopulation of cells in the adipose tissue of mice . A combined technique of single‐cell RNA‐sequencing and FACS isolation was utilized to identify the so called fibro‐inflammatory progenitors (FIPs) cells residing around the blood vessels in the visceral adipose tissue of mice . FIPs can activate immune cells in WAT and contribute to WAT remodeling and fibrosis …”

Deep generative model embedding of single-cell RNA-Seq profiles on hyperspheres and hyperbolic spaces

“…This result generalized across multiple datasets of diverse biological systems, including 3,314 human lung cells (Braga et al, 2019) ( Fig. 2A), 1,378 mouse white adipose tissue stromal cells (Hepler et al, 2018) (Fig. 2B), and 1,755 human splenic nature killer cells spanning four subtypes (Fig.…”

Skin and subcutaneous fat morphology alterations under the LED or laser treatment in rats in vivo

“…Unhealthy fat tissue contains enlarged fat cells, which may die from stress. The stress this places on the surrounding tissue activates the immune system, causing inflammation and the build‐up of collagen fibers around the cells (a condition known as fibrosis) . We are inspired by the fact that in 2 weeks after treatment we observed no inflammation signs in the animal skin and in the dermis.…”