Defining the role of pulmonary endothelial cell heterogeneity in the response to acute lung injury
- University of Pennsylvania, United States
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.
Data availability
Single-cell RNA sequencing datasets have been deposited in GEO under accession code GSE128944.
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Defining the role of pulmonary endothelial cell heterogeneity in the response to acute lung injuryNCBI Gene Expression Omnibus, GSE128944.
Article and author information
Author details
Funding
National Institutes of Health (R01-HL087825)
- Edward E Morrisey
National Institutes of Health (U01-HL134745-01)
- Edward E Morrisey
National Institutes of Health (R01-HL132999)
- Edward E Morrisey
National Institutes of Health (R01-HL132349)
- Edward E Morrisey
National Institutes of Health (T32-HL7586-34)
- Terren K Niethamer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Gordana Vunjak-Novakovic, Columbia University, United States
Ethics
Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Care and use of Laboratory Animals and under the oversight of the Institutional Animal Care and Use Committee (IACUC) of the University of Pennsylvania. All mouse experiments were approved by IACUC under protocol #806345.
Version history
- Received: October 26, 2019
- Accepted: February 22, 2020
- Accepted Manuscript published: February 24, 2020 (version 1)
- Version of Record published: April 22, 2020 (version 2)
Copyright
© 2020, Niethamer et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Defining the role of pulmonary endothelial cell heterogeneity in the response to acute lung injury
eLife 9:e53072.
https://doi.org/10.7554/eLife.53072
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