Characterization of the Arterial Adventitia as a Sonic Hedgehog Responsive Niche

While formerly viewed as merely connective tissue, the emerging view of the arterial adventitia is that of a complex and organized vascular progenitor cell niche. Previously, our lab has identified a domain of Sonic Hedgehog (Shh) signaling restricted to the adventitia. This domain is locally produced and maintained, with the peak of activity being during embryonic and neonatal development of the vessel from embryonic day 14.5 (e14.5) to postnatal day 14 in the mouse. Developmental studies suggest that the mesenchyme continuous with the perichondrium of the axial skeleton contains Shh responsive cells that may contribute to adventitial development around e14.5. The cell types that participate in this Sonic Hedgehog adventitial signaling community are CD68-positive macrophages, Sca1-positive progenitor cells, and Perilipin A-positive adipocytes that make and/or respond to Shh protein as shown using transgenic reporter mice. Thus, we characterize the adventitia as a Shh responsive vascular niche

Vascular Smooth Muscle Progenitor Cells: Building and Repairing Blood Vessels

Molecular pathways that control the specification, migration, and number of available smooth muscle progenitor cells play key roles in determining blood vessel size and structure, capacity for tissue repair and remodeling, and progression of age-related disorders. Defects in these pathways will produce malformations of developing blood vessels, depletion of SMC progenitor pools for vessel wall maintenance and repair, and aberrant activation of alternative differentiation pathways in vascular disease. A better understanding of the molecular mechanisms that uniquely specify and maintain vascular SMC precursors is essential if we are to utilize advances in stem and progenitor cell biology and somatic cell reprogramming for applications directed to the vessel wall