Abstract
Adipose progenitor cells (APCs) reside in a vascular niche, located within the perivascular compartment of adipose tissue blood vessels. Yet, the signals and mechanisms that govern adipose vascular niche formation and APC niche interaction are unknown. Here we show that the assembly and maintenance of the adipose vascular niche is controlled by PPARγ acting within APCs. PPARγ triggers a molecular hierarchy that induces vascular sprouting, APC vessel niche affinity and APC vessel occupancy. Mechanistically, PPARγ transcriptionally activates PDGFRβ and VEGF. APC expression and activation of PDGFRβ promotes the recruitment and retention of APCs to the niche. Pharmacologically, targeting PDGFRβ disrupts APC niche contact thus blocking adipose tissue expansion. Moreover, enhanced APC expression of VEGF stimulates endothelial cell proliferation and expands the adipose niche. Consequently, APC niche communication and retention are boosted by VEGF thereby impairing adipogenesis. Our data indicate that APCs direct adipose tissue niche expansion via a PPARγ-initiated PDGFRβ and VEGF transcriptional axis.
Highlights
Adipose progenitor cells (APCs) reside in a vascular niche, located within the perivascular compartment of adipose tissue blood vessels
Our studies suggest that adult APCs control the expansion and maintenance of their own niche through a peroxisome proliferatoractivated receptor gamma (PPARg) to PDGFRb and PPARg to VEGF molecular network, which can influence adiposity and systemic metabolism
The two LOF strategies altered Pparg expression in the intended manner based upon quantitative real-time PCR analyses of fluorescence-activated cell sorting (FACS)-isolated green fluorescent protein-positive (GFP þ ) progenitors and both mice were lipodystrophic as previously described (Fig. 1b and Supplementary Fig. 1a–c)[10,23]
Summary
Adipose progenitor cells (APCs) reside in a vascular niche, located within the perivascular compartment of adipose tissue blood vessels. PPARg is a nuclear hormone receptor and a master transcriptional regulator of adipocyte differentiation[19,20,21] These adult APCs acquire vascular residence after a distinct and independent developmental APC compartment forms the adipose depots during adipose tissue organogenesis; APCs are not born on blood vessels rather they migrate, adhere and reside in perivascular positions[10,12,13,22]. PPARg controls niche expansion by stimulating APC niche interaction and retention and by increasing vasculogenesis via a transcriptional network that includes platelet-derived growth factor receptor beta (Pdgfrb) and vascular endothelial growth factor (Vegf). Our studies suggest that adult APCs control the expansion and maintenance of their own niche through a PPARg to PDGFRb and PPARg to VEGF molecular network, which can influence adiposity and systemic metabolism
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