Abstract
Pulmonary endothelial cells (PECs) are indispensable for sustaining lung microenvironmental homeostasis and exert significant influence across a spectrum of pulmonary pathologies. Single-cell RNA sequencing (scRNA-seq) has fundamentally transformed conventional paradigms surrounding PECs, unveiling novel perspectives on their roles in both physiological and pathological lung conditions. This technology provides critical insights into the phenotypic diversity and distinct molecular signatures of PECs, underscoring their substantial heterogeneity in structure, function and gene expression, which is contingent upon their spatial localization within the lung microenvironment. The advancements in scRNA-seq have catalyzed remarkable progress in the therapeutic management of pulmonary pathophysiology, facilitating breakthroughs in the identification of cellular subpopulations, functional characterization and discovery of innovative therapeutic targets. In this review, we systematically synthesize the markers and subclusters of PECs as delineated by scRNA-seq, elucidate their applications in normal and pathological lung contexts, and propose future directions regarding molecular mechanisms and therapeutic interventions targeting PECs.