Dynamic behavior and lineage plasticity of the pulmonary venous endothelium

Repair of the pulmonary vascular bed and the origin of new vasculature remain underexplored despite the critical necessity to meet oxygen demands after injury. Given their critical role in angiogenesis in other settings, we investigated the role of venous endothelial cells in endothelial regeneration after adult lung injury. Here we identified Slc6a2 as a marker of pulmonary venous endothelial cells and generated a venous-specific, inducible Cre mouse line. We observed that venous endothelial cells proliferate into the adjacent capillary bed upon influenza injury and hyperoxia injury. Imaging analysis demonstrated that venous endothelial cells proliferate and differentiate into general capillary and aerocyte capillary endothelial cells after infection, thus contributing to repair of the capillary plexus vital for gas exchange. Our studies thus establish that venous endothelial cells exhibit demonstrable progenitor capacity upon respiratory viral injury and sterile injury, contributing to repair of the alveolar capillary bed responsible for pulmonary function.