Abstract 17158: 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 & 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-CreER, 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 (<5%), somite-derived Sca-1+ cells proliferate in situ and become the dominant source of aortic Sca-1+ cells (>50%) by 6 weeks of age. Pulse-chase in 8 week old tamoxifen-inducible Sox2-reporter mice (Sox2-CreERT2) 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.
Author Disclosures: S.K. Steinbach: None. A. Li: None. R. Besla: None. S. Li: None. M. Carruthers: None. A. Johnston: None. R. Li: None. M. Ouzounian: None. C. Robbins: None. M. Husain: None.
- © 2016 by American Heart Association, Inc.