Endothelial Continuum and Capillary Specialization in Pulmonary Vascular Development.

Abstract

Pulmonary vascular development requires coordinated growth, remodeling, and specialization of the endothelial network to support airway branching and alveolar formation. Recent advances in single-cell and spatial transcriptomics have revealed that endothelial cells are organized along a transcriptional arteriovenous spectrum while simultaneously adopting region-specific identities within the capillary bed. In particular, the emergence of distinct alveolar capillary populations, including capillary endothelial cell type 1 and capillary endothelial cell type 2 cells, highlights previously unappreciated heterogeneity. Parallel studies further demonstrate that macrovascular and microvascular identities are influenced by positional context, vessel caliber, and flow-associated transcriptional programs. Together, these insights redefine how endothelial specialization is established during lung development. Here, we review current understanding of pulmonary vascular morphogenesis, endothelial fate specification, and capillary diversification and discuss how emerging imaging platforms may help connect molecular identity with spatial organization and dynamic cellular behavior.