Lineage tracing reveals a shared cellular origin for supraclavicular brown and inguinal beige adipocytes

The metabolic importance of brown adipose tissue (BAT) has been recognized, but its origins, particularly supraclavicular BAT (scBAT), remain unclear. Here, we traced scBAT to Mef2c-anterior heart field (AHF)-marked cells. Mef2c-AHF-marked cells isolated from scBAT can spontaneously differentiate into brown adipocytes, express mesenchymal stem cell markers, and can be isolated from the stromal-vascular fraction (SVF) of wild-type scBAT as [CD31^-CD45^-Sca-1⁺CD29⁺CD34^-CD24^-] (CD34^-) cells. Mef2c-AHF-marked cells substantially overlap with Prrx1-marked cells in scBAT, which also contribute to beige adipocytes in inguinal white adipose tissue (iWAT). Similarly, CD34^- cells isolated from the SVF of iWAT can spontaneously differentiate into beige adipocytes in vitro. Intersectional lineage tracing shows that common progenitors of Mef2c-AHF- and Prrx1-marked cells in scBAT emerge from the developing heart. Thus, these studies reveal a common origin for scBAT and cardiac tissue and suggest that scBAT and iWAT beige adipocytes arise from progenitor populations with overlapping lineage origins and molecular characteristics.