Myf5 Progenitors Define the Lineage Identity of Somitic Vascular Smooth Muscle Cells

Vascular smooth muscle cell (VSMC) heterogeneity drives region-specific aortic pathologies, yet the roles of somite-derived lineages remain unclear. Utilizing Myf5 and MyoD lineage tracing alongside a smooth muscle-specific Myf5 conditional knockout model, we show that Myf5-derived cells selectively populate the thoracic aortic media, whereas the MyoD lineage completely spares large arteries. Early embryonic Myf5 deletion suppressed embryonic VSMC proliferation and downregulated α-SMA, reduced the synthesis of elastic, establishing its necessity in aortic morphogenesis. Upon in vitro ox-LDL challenge and calcification induction, the non-Myf5 lineage primarily drives excessive proliferation and osteogenic transdifferentiation, whereas Myf5 lineage VSMCs exhibit remarkable phenotypic stability and resistance to PDGF-BB-induced dedifferentiation compared to their non-Myf5 counterparts. Collectively, our findings demonstrate a strict lineage divergence between Myf5 and MyoD, suggesting that Myf5 lineage cells play an important role in maintaining aortic integrity, and uncover a lineage-imprinted plasticity that explains regional vascular heterogeneity.