Vascular smooth muscle-derived TRPV1-positive progenitors are a source of cold-induced thermogenic adipocytes

Brown adipose tissue (BAT) and beige fat function in energy expenditure in part due to their role in thermoregulation, making these tissues attractive targets for treating obesity and metabolic disorders. While prolonged cold exposure promotes de novo recruitment of brown adipocytes, the exact sources of cold-induced thermogenic adipocytes are not completely understood. Here, we identify Trpv1-positive vascular smooth muscle (VSM) cells as previously unidentified brown adipocyte progenitors. Analysis of single-cell RNA sequencing from interscapular brown adipose depots reveals, in addition to the previously-known Pdgfra-expressing mesenchymal progenitors, a previously-unidentified VSM-derived adipocyte progenitor (APC) population, which expresses the temperature-sensitive cation channel, Trpv1. Using flow cytometry and lineage tracing, we demonstrate that the Trpv1-positive VSM-APCs are distinct from the Pdgfra-positive progenitors, and can give rise to thermogenic adipocytes in response to cold. Together, these findings illustrate the landscape of the thermogenic adipose niche at the single cell resolution and identify a new cellular origin for the development of brown and beige adipocytes.