1. Stem Cells and Regenerative Medicine
Download icon

Defining the role of pulmonary endothelial cell heterogeneity in the response to acute lung injury

Research Article
  • Cited 1
  • Views 661
  • Annotations
Cite this article as: eLife 2020;9:e53072 doi: 10.7554/eLife.53072

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.

Article and author information

Author details

  1. Terren K Niethamer

    Department of Medicine, Department of Cell and Developmental Biology, Penn Center for Pulmonary Biology, Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, United States
    Competing interests
    No competing interests declared.
  2. Collin T Stabler

    Department of Medicine, Department of Cell and Developmental Biology, Penn Center for Pulmonary Biology, Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, United States
    Competing interests
    No competing interests declared.
  3. John P Leach

    Department of Medicine, Department of Cell and Developmental Biology, Penn Center for Pulmonary Biology, Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, United States
    Competing interests
    No competing interests declared.
  4. Jarod A Zepp

    Department of Medicine, Department of Cell and Developmental Biology, Penn Center for Pulmonary Biology, Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, United States
    Competing interests
    No competing interests declared.
  5. Michael P Morley

    Department of Medicine, Penn Center for Pulmonary Biology, Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, United States
    Competing interests
    No competing interests declared.
  6. Apoorva Babu

    Department of Medicine, Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, United States
    Competing interests
    No competing interests declared.
  7. Su Zhou

    Department of Medicine, Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, United States
    Competing interests
    No competing interests declared.
  8. Edward E Morrisey

    Department of Medicine, Department of Cell and Developmental Biology, Penn-CHOP Lung Biology Institute, Penn Cardiovascular Institute, Penn Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, United States
    For correspondence
    emorrise@pennmedicine.upenn.edu
    Competing interests
    Edward E Morrisey, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5785-1939

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.

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.

Reviewing Editor

  1. Gordana Vunjak-Novakovic, Columbia University, United States

Publication history

  1. Received: October 26, 2019
  2. Accepted: February 22, 2020
  3. Accepted Manuscript published: February 24, 2020 (version 1)

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.

Metrics

  • 661
    Page views
  • 239
    Downloads
  • 1
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine
    Alexandra Schauer et al.
    Research Article
    1. Genetics and Genomics
    2. Stem Cells and Regenerative Medicine
    David J Forsthoefel et al.
    Tools and Resources