Daniel F. Bowen-Pope, PhD
The possibility that some vascular cells derive from extravascular progenitors is no longer controversial, but experimental limitations have prevented agreement as to the magnitude of the contribution, whether/when it is physiologically significant, and whether it can be manipulated for clinical benefit. We will trace, and specifically ablate, vascular endothelial cell and smooth muscle cell lineages using cell type-specific expression of reporter/effector fusion proteins that include EGFP and a domain that mediates apoptotic cell death when activated by injectable dimerizer. Using mice with transgenic bone marrow systems, we will:
- quantitate the contribution of bone marrow-derived progenitors to new vessel formation,
- determine whether vascular cells derived from extravascular vs local vascular sources differ in final phenotype, and
- use the dimerizer-activated apoptotic effector to evaluate the function of extravascular progenitors by selective ablation of this contribution during new vessel formation.