Abstract
Studies have demonstrated the phenotypic heterogeneity of vascular endothelial cells (ECs) within a vascular bed; however, little is known about how distinct endothelial subpopulations in a particular organ respond to an inflammatory stimulus. We performed single-cell RNA-Seq of 35,973 lung ECs obtained during baseline as well as postinjury time points after inflammatory lung injury induced by LPS. Seurat clustering and gene expression pathway analysis identified 2 major subpopulations in the lung microvascular endothelium, a subpopulation enriched for expression of immune response genes such as MHC genes (immuneEC) and another defined by increased expression of vascular development genes such as Sox17 (devEC). The presence of immuneEC and devEC subpopulations was also observed in nonhuman primate lungs infected with SARS-CoV-2 and murine lungs infected with H1N1 influenza virus. After the peak of inflammatory injury, we observed the emergence of a proliferative lung EC subpopulation. Overexpression of Sox17 prevented inflammatory activation in ECs. Thus, there appeared to be a “division of labor” within the lung microvascular endothelium in which some ECs showed propensity for inflammatory signaling and others for endothelial regeneration. These results provide underpinnings for the development of targeted therapies to limit inflammatory lung injury and promote regeneration.
Keywords: Bacterial infections; Endothelial cells; Infectious disease; Influenza; Pulmonology.
【저자키워드】 Influenza, Infectious disease, endothelial cells, Bacterial infections, Pulmonology, 【초록키워드】 Gene Expression, Influenza, lung, Infectious disease, Lung injury, virus, heterogeneity, Pathway analysis, Endothelium, endothelial cells, single-cell RNA-seq, Clustering, immune response genes, H1N1, targeted therapy, H1N1 influenza, expression, Bacterial infections, single-cell, LPS, Inflammatory, Injury, regeneration, Pulmonology, immune response gene, endothelial, Activation, Vascular, increased expression, vascular endothelial cells, labor, phenotypic, overexpression, organ, division, subpopulation, inflammatory lung injury, murine, H1N1 influenza virus, MHC genes, vascular endothelial cell, limit, inflammatory signaling, Seurat, Sox17, vascular bed, defined, performed, demonstrated, promote, prevented, respond, proliferative, baseline, infected with SARS-CoV-2, MHC gene, 【제목키워드】 endothelial cells, regenerative, Inflammatory, lung endothelial, transcriptomic, Cell, identify,