Somitic Mesoderm-derived and Sox2(+) Stem Cells Give Rise To Sca-1(+) Progenitor Cells in Mouse Aorta

Rationale: Sca-1 + progenitor cells in mouse aorta are known to generate vascular cells. However, their embryological origins and temporospatial abundance during development were not known. Objective: To describe stem cells of the mouse aorta and identify lineages of Sca-1 + progenitors. Methods u0026 Results: Lineage-traced reporter mice at 8+ weeks of age reveal aortic stem cells, defined as self-renewing colony-forming cells with multi-lineage potential, to be most abundant in proximal aorta and predominantly of mesodermal origin ( T-Cre ), with little, if any, from neural crest ( Wnt1-Cre ). In distal aorta, the few stem cells that exist are strictly of mesodermal origin. Clonal cell colonies can be cultured in suspension from aorta-derived stem cells of somitic mesoderm origin ( Myf5-Cre ), and contain cells expressing stem cell marker Sox2. Using tamoxifen-inducible Myf5-Cre ER , we show that Sca-1 + aortic cells from somite are specified at E8.5, even before Myf5 + cells contribute to skeletal muscle. While contributing minimally to aortic Sca-1 + cells immediately after birth ( + cells proliferate in situ and become the dominant source of aortic Sca-1 + cells (u003e50%) by 6 weeks of age. Pulse-chase in 8 week old tamoxifen-inducible Sox2-reporter mice ( Sox2-Cre ERT2 ) revealed that ~35% of all aortic Sca-1 + are derived from Sox2 + cells 8 weeks later. In human aorta, Sox2 + cells correlated with aneurysmal dilatation. Conclusion: Proportions of mouse aortic Sca-1 + progenitor cells from somitic mesoderm and Sox2 + stem cells vary by aortic location and developmental stage, undergoing continuous steady state renewal into adulthood. Abundance of Sox2 + cells in human aorta correlates with disease.