1. Defining the role of pulmonary endothelial cell heterogeneity in the response to acute lung injury.
- Author
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Niethamer TK, Stabler CT, Leach JP, Zepp JA, Morley MP, Babu A, Zhou S, and Morrisey EE
- Subjects
- Animals, Endothelium pathology, Endothelium, Vascular cytology, Endothelium, Vascular pathology, Female, Flow Cytometry, Lung pathology, Mice, Mice, Inbred C57BL, Neovascularization, Physiologic, Orthomyxoviridae Infections pathology, Pulmonary Alveoli cytology, Pulmonary Alveoli pathology, Single-Cell Analysis, Acute Lung Injury pathology, Endothelium cytology, Lung cytology
- Abstract
Pulmonary endothelial cells (ECs) are an essential component of the gas exchange machinery of the lung alveolus. Despite this, the extent and function of lung EC heterogeneity remains incompletely understood. Using single-cell analytics, we identify multiple EC populations in the mouse lung, including macrovascular endothelium (maEC), microvascular endothelium (miECs), and a new population we have termed Car4 -high ECs. Car4 -high ECs express a unique gene signature, and ligand-receptor analysis indicates they are primed to receive reparative signals from alveolar type I cells. After acute lung injury, they are preferentially localized in regenerating regions of the alveolus. Influenza infection reveals the emergence of a population of highly proliferative ECs that likely arise from multiple miEC populations and contribute to alveolar revascularization after injury. These studies map EC heterogeneity in the adult lung and characterize the response of novel EC subpopulations required for tissue regeneration after acute lung injury., Competing Interests: TN, CS, JL, JZ, MM, AB, SZ No competing interests declared, EM Reviewing editor, eLife, (© 2020, Niethamer et al.)
- Published
- 2020
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