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...

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Main Authors: Terren K Niethamer, Collin T Stabler, John P Leach, Jarod A Zepp, Michael P Morley, Apoorva Babu, Su Zhou, Edward E Morrisey
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2020-02-01
Series:eLife
Subjects:
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.
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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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