Defining the role of pulmonary endothelial cell heterogeneity in the response to acute lung injury
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, includi...
Main Authors: | , , , , , , , |
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Format: | Article |
Language: | English |
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eLife Sciences Publications Ltd
2020-02-01
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Series: | eLife |
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Online Access: | https://elifesciences.org/articles/53072 |
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author | Terren K Niethamer Collin T Stabler John P Leach Jarod A Zepp Michael P Morley Apoorva Babu Su Zhou Edward E Morrisey |
author_facet | Terren K Niethamer Collin T Stabler John P Leach Jarod A Zepp Michael P Morley Apoorva Babu Su Zhou Edward E Morrisey |
author_sort | Terren K Niethamer |
collection | DOAJ |
description | 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. |
first_indexed | 2024-04-14T07:34:22Z |
format | Article |
id | doaj.art-d837fd8d09934d93be1199f326a91e3e |
institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-14T07:34:22Z |
publishDate | 2020-02-01 |
publisher | eLife Sciences Publications Ltd |
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series | eLife |
spelling | doaj.art-d837fd8d09934d93be1199f326a91e3e2022-12-22T02:05:45ZengeLife Sciences Publications LtdeLife2050-084X2020-02-01910.7554/eLife.53072Defining the role of pulmonary endothelial cell heterogeneity in the response to acute lung injuryTerren K Niethamer0https://orcid.org/0000-0002-0914-994XCollin T Stabler1John P Leach2Jarod A Zepp3Michael P Morley4Apoorva Babu5Su Zhou6Edward E Morrisey7https://orcid.org/0000-0001-5785-1939Department of Medicine, University of Pennsylvania, Philadelphia, United States; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, United States; Penn-Children's Hospital of Philadelphia Lung Biology Institute, University of Pennsylvania, Philadelphia, United States; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, United StatesDepartment of Medicine, University of Pennsylvania, Philadelphia, United States; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, United States; Penn-Children's Hospital of Philadelphia Lung Biology Institute, University of Pennsylvania, Philadelphia, United States; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, United StatesDepartment of Medicine, University of Pennsylvania, Philadelphia, United States; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, United States; Penn-Children's Hospital of Philadelphia Lung Biology Institute, University of Pennsylvania, Philadelphia, United States; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, United StatesDepartment of Medicine, University of Pennsylvania, Philadelphia, United States; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, United States; Penn-Children's Hospital of Philadelphia Lung Biology Institute, University of Pennsylvania, Philadelphia, United States; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, United StatesDepartment of Medicine, University of Pennsylvania, Philadelphia, United States; Penn-Children's Hospital of Philadelphia Lung Biology Institute, University of Pennsylvania, Philadelphia, United States; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, United StatesDepartment of Medicine, University of Pennsylvania, Philadelphia, United States; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, United StatesDepartment of Medicine, University of Pennsylvania, Philadelphia, United States; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, United StatesDepartment of Medicine, University of Pennsylvania, Philadelphia, United States; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, United States; Penn-Children's Hospital of Philadelphia Lung Biology Institute, University of Pennsylvania, Philadelphia, United States; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, United States; Penn Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, United StatesPulmonary 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.https://elifesciences.org/articles/53072pulmonary endothelial cellsvascular biologylung regenerationacute lung injury |
spellingShingle | Terren K Niethamer Collin T Stabler John P Leach Jarod A Zepp Michael P Morley Apoorva Babu Su Zhou Edward E Morrisey Defining the role of pulmonary endothelial cell heterogeneity in the response to acute lung injury eLife pulmonary endothelial cells vascular biology lung regeneration acute lung injury |
title | Defining the role of pulmonary endothelial cell heterogeneity in the response to acute lung injury |
title_full | Defining the role of pulmonary endothelial cell heterogeneity in the response to acute lung injury |
title_fullStr | Defining the role of pulmonary endothelial cell heterogeneity in the response to acute lung injury |
title_full_unstemmed | Defining the role of pulmonary endothelial cell heterogeneity in the response to acute lung injury |
title_short | Defining the role of pulmonary endothelial cell heterogeneity in the response to acute lung injury |
title_sort | defining the role of pulmonary endothelial cell heterogeneity in the response to acute lung injury |
topic | pulmonary endothelial cells vascular biology lung regeneration acute lung injury |
url | https://elifesciences.org/articles/53072 |
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