Tissue resident macrophages promote extracellular matrix homeostasis in the mammary gland stroma of nulliparous mice
- University of Minnesota, United States
- Tulane University, United States
- 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.
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Single cell analysis of immune cell populations in mammary glands from 10-week-old miceNCBI Gene Expression Omnibus, GSE148209.
Article and author information
Author details
Kathryn L Schwertfeger
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
- Carla V Rothlin, Yale School of Medicine, United States
Publication history
- Received: March 31, 2020
- Accepted: May 31, 2020
- Accepted Manuscript published: June 1, 2020 (version 1)
- Version of Record published: June 16, 2020 (version 2)
- 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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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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Structural and physiological changes in the female reproductive system underlie the origins of pregnancy in multiple vertebrate lineages. In mammals, the glandular portion of the lower reproductive tract has transformed into a structure specialized for supporting fetal development. These specializations range from relatively simple maternal nutrient provisioning in egg-laying monotremes to an elaborate suite of traits that support intimate maternal-fetal interactions in Eutherians. Among these traits are the maternal decidua and fetal component of the placenta, but there is considerable uncertainty about how these structures evolved. Previously we showed that changes in uterine gene expression contributes to several evolutionary innovations during the origins of pregnancy (Marinic, Mika, and Lynch 2021). Here we reconstruct the evolution of entire transcriptomes ('ancestral transcriptome reconstruction') and show that maternal gene expression profiles are correlated with degree of placental invasion. These results indicate that an epitheliochorial-like placenta evolved early in the mammalian stem-lineage and that the ancestor of Eutherians had a hemochorial placenta, and suggest maternal control of placental invasiveness. These data resolve major transitions in the evolution of pregnancy and indicate that ancestral transcriptome reconstruction can be used to study the function of ancestral cell, tissue, and organ systems.
