Aortic Sca-1⁺ Progenitor Cells Arise from the Somitic Mesoderm Lineage in Mice

Sca-1⁺ progenitor cells in the adult mouse aorta are known to generate vascular smooth muscle cells (VSMCs), but their embryological origins and temporal abundance are not known. Using tamoxifen-inducible Myf5-Cre^ER mice, we demonstrate that Sca-1⁺ adult aortic cells arise from the somitic mesoderm beginning at E8.5 and continue throughout somitogenesis. Myf5 lineage-derived Sca-1⁺ cells greatly expand in situ, starting at 4 weeks of age, and become a major source of aortic Sca-1⁺ cells by 6 weeks of age. Myf5-derived adult aortic cells are capable of forming multicellular sphere-like structures in vitro and express the pluripotency marker Sox2. Exposure to transforming growth factor-β3 induces these spheres to differentiate into calponin-expressing VSMCs. Pulse-chase experiments using tamoxifen-inducible Sox2-Cre^ERT2 mice at 8 weeks of age demonstrate that ∼35% of all adult aortic Sca-1⁺ cells are derived from Sox2⁺ cells. The present study demonstrates that aortic Sca-1⁺ progenitor cells are derived from the somitic mesoderm formed at the earliest stages of somitogenesis and from Sox2-expressing progenitors in adult mice.