Defining the lineage of thermogenic perivascular adipose tissue

Abstract

SummaryBrown adipose tissue can expend large amounts of energy and thus increasing its amount or activity is a promising therapeutic approach to combat metabolic disease. In humans, major deposits of brown fat cells are found intimately associated with large blood vessels, corresponding to perivascular adipose tissue (PVAT). However, the cellular origins of PVAT are poorly understood. Here, we applied single cell transcriptomic analyses, ex vivo adipogenesis assays, and genetic fate mapping in vivo to determine the identity of perivascular adipocyte progenitors. We found that thoracic PVAT initially develops from a fibroblastic lineage, comprising progenitor cells (Pdgfra+;Ly6a+;Pparg−) and preadipocytes (Pdgfra+;Ly6a−;Pparg+). Progenitors and preadipocytes in PVAT shared transcriptional similarity with analogous cell types in white adipose tissue, pointing towards a conserved adipose cell lineage hierarchy. Interestingly, the aortic adventitia of adult animals contained a novel population of adipogenic smooth muscle cells (Myh11+; Pdgfra−; Pparg+) possessing the capacity to generate adipocytes in vitro and in vivo. Taken together, these studies define distinct populations of fibroblastic and smooth muscle progenitor cells for thermogenic PVAT, providing a crucial foundation for developing strategies to augment brown fat activity.Competing Interest StatementThe authors have declared no competing interest.View Full Text