NAP1‐L1 determines progenitor status of pulmonary endothelium

Abstract

Pulmonary MicroVascular Endothelial Cells (PMVECs) are enriched with progenitors that display enhanced proliferative and self‐renewal capacity. Since expression of Nucleosome Assembly Protein 1 Like 1 (NAP1‐L1) regulates cell proliferation, we sought to determine whether NAP1‐L1 determines the progenitor status of PMVECs. PMVECs subjected to the single cell clonogenic assay revealed that 20% of the population were fully differentiated (do not proliferate), 30% exhibited low proliferative potential (LPP) and 50% exhibited high proliferative potential (HPP). Re‐seeding cells in the clonogenic assay revealed that HPPs, but not LPPs, reconstituted the hierarchy of growth potentials, an indication of the HPPs self‐renewal capacity, and thus confirming their progenitor status. While NAP1‐L1 expression was increased in HPPs compared to LPPs, NAP1‐L1 overexpression in LPPs confered them with a progenitor status where 40% of the cells exhibited HPP‐ and self‐renewal capability. Immunohistochemical analysis in lungs from rats infected with Pseudomonas aeruginosa revealed that within injured, but not normal lung areas, there were endothelial cells that retained the proliferative marker Brdu and expressed NAP1‐L1. We conclude that NAP1‐L1 determines the progenitor status of pulmonary endothelium and associates in situ within vessels containing highly replicative endothelial cells. AHA 0835134N