PDGF receptor signal mediates the contribution of Nestin-positive cell lineage to subcutaneous fat development

The beiging of white adipose tissue (WAT) is expected to improve systemic metabolic conditions; however, the regulation and developmental origin of this process remain insufficiently understood. In the present study, the implication of platelet-derived growth factor receptor alpha (PDGFRa) was examined in the beiging of inguinal WAT (ingWAT) of neonatal mice. Using in vivo Nestin expressing cell (Nestin+) lineage tracing and deletion mouse models, we found that, in the mice with Pdgfra gene inactivation in Nestin+ lineage (N-PRa-KO mice), the growth of inguinal WAT (ingWAT) was suppressed during neonatal periods as compared with control wild-type mice. In the ingWAT of N-PRa-KO mice, the beige adipocytes appeared earlier that were accompanied by the increased expressions of both adipo-genic and beiging markers compared to control wild-type mice. In the perivascular adipocyte progenitor cell (APC) niche of ingWAT, many PDGFRa+ cells of Nestin+ lineage were recruited in Pdgfra-preserving control mice, but were largely decreased in N-PRa-KO mice. This PDGFRa+ cell depletion was replenished by PDGFRa+ cells of non-Nestin+ lineage, unexpectedly resulting in an increase of total PDGFRa+ cell number in APC niche of N-PRa-KO mice over that of control mice. These represented a potent homeo-static control of PDGFRa+ cells between Nestin+ and non-Nestin+ lineages that was accompanied by the active adipogenesis and beiging as well as small WAT depot. This highly plastic nature of PDGFRa+ cells in APC niche may contribute to the WAT remodeling for the therapeutic purpose against metabolic diseases.(c) 2023 Elsevier Inc. All rights reserved.