Tissue resident macrophages promote extracellular matrix homeostasis in the mammary gland stroma of nulliparous mice

  1. Ying Wang
  2. Thomas S Chaffee
  3. Rebecca S LaRue
  4. Danielle N Huggins
  5. Patrice M Witschen
  6. Ayman M Ibrahim
  7. Andrew C Nelson
  8. Heather L Machado
  9. Kathryn L Schwertfeger  Is a corresponding author
  1. University of Minnesota, United States
  2. Tulane University, United States
  3. Tulane Cancer Center, Tulane School of Medicine, United States

Abstract

Tissue resident macrophages in the mammary gland are found in close association with epithelial structures and within the adipose stroma, and are important for mammary gland development and tissue homeostasis. While macrophages have been linked to ductal development in the virgin mammary gland, less is known regarding the effects of macrophages on the adipose stroma. Using transcriptional profiling and single cell RNA sequencing approaches, we identify a distinct resident stromal macrophage subpopulation within the mouse nulliparous mammary gland characterized by expression of Lyve-1, a receptor for the extracellular matrix (ECM) component hyaluronan. This subpopulation is enriched in genes associated with ECM remodeling and is specifically associated with hyaluronan-rich regions within the adipose stroma and fibrous capsule of the virgin mammary gland. Furthermore, macrophage depletion leads to enhanced accumulation of hyaluronan-associated ECM in the adipose-associated stroma, indicating that resident macrophages are important for maintaining homeostasis within the nulliparous mammary gland stroma.

Data availability

Sequencing data have been deposited in GEO under accession codes GSE148207 and GSE148209.

The following data sets were generated

Article and author information

Author details

  1. Ying Wang

    Lab Medicine and Pathology, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Thomas S Chaffee

    Lab Medicine and Pathology, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Rebecca S LaRue

    Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Danielle N Huggins

    Lab Medicine and Pathology, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Patrice M Witschen

    Lab Medicine and Pathology, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Ayman M Ibrahim

    Department of Biochemistry and Molecular Biology, Tulane University, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Andrew C Nelson

    Lab Medicine and Pathology, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Heather L Machado

    Department of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Kathryn L Schwertfeger

    Department of Pharmacology, University of Minnesota, Minneapolis, United States
    For correspondence
    schwe251@umn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9755-7774

Funding

National Institutes of Health (T 32 fellowship,OD010993)

  • Patrice M Witschen

American Cancer Society (Post-doctoral fellowship,132570-PF-18-140-01-CSM)

  • Danielle N Huggins

American Cancer Society (Clinical Scholar Development Grant,132574-CSDG-18-139-01-CSM)

  • Andrew C Nelson

National Institutes of Health (R01CA212518)

  • Heather L Machado

National Institutes of Health (R01HD095858)

  • Kathryn L Schwertfeger

National Institutes of Health (R01CA235385)

  • Kathryn L Schwertfeger

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal care and procedures were approved by the Institutional Animal Care and Use Committees of the University of Minnesota (protocol #1909-37381A) and Tulane University (protocol #710) and were in accordance with the procedures detailed in the Guide for Care and Use of Laboratory Animals.

Human subjects: The study was approved for exemption (#00008356) by the Institutional Review Board at the University of Minnesota and all patients had accepted the institutional standard consent for research utilization of clinical data and samples. All patient materials were de-identified following standard protocols.

Reviewing Editor

  1. Carla V Rothlin, Yale School of Medicine, United States

Publication history

  1. Received: March 31, 2020
  2. Accepted: May 31, 2020
  3. Accepted Manuscript published: June 1, 2020 (version 1)
  4. Version of Record published: June 16, 2020 (version 2)
  5. Version of Record updated: July 2, 2020 (version 3)

Copyright

© 2020, Wang 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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  1. Ying Wang
  2. Thomas S Chaffee
  3. Rebecca S LaRue
  4. Danielle N Huggins
  5. Patrice M Witschen
  6. Ayman M Ibrahim
  7. Andrew C Nelson
  8. Heather L Machado
  9. Kathryn L Schwertfeger
(2020)
Tissue resident macrophages promote extracellular matrix homeostasis in the mammary gland stroma of nulliparous mice
eLife 9:e57438.
https://doi.org/10.7554/eLife.57438

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