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.
-
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.
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.
Metrics
-
- 7,419
- views
-
- 671
- downloads
-
- 64
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
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)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
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
Further reading
-
- Developmental Biology
Mutations in the well-known Myostatin (MSTN) produce a ‘double-muscle’ phenotype, which makes it commercially invaluable for improving livestock meat production and providing high-quality protein for humans. However, mutations at different loci of the MSTN often produce a variety of different phenotypes. In the current study, we increased the delivery ratio of Cas9 mRNA to sgRNA from the traditional 1:2 to 1:10, which improves the efficiency of the homozygous mutation of biallelic gene. Here, a MSTNDel73C mutation with FGF5 knockout sheep, in which the MSTN and FGF5 dual-gene biallelic homozygous mutations were produced via the deletion of 3-base pairs of AGC in the third exon of MSTN, resulting in cysteine-depleted at amino acid position 73, and the FGF5 double allele mutation led to inactivation of FGF5 gene. The MSTNDel73C mutation with FGF5 knockout sheep highlights a dominant ‘double-muscle’ phenotype, which can be stably inherited. Both F0 and F1 generation mutants highlight the excellent trait of high-yield meat with a smaller cross-sectional area and higher number of muscle fibers per unit area. Mechanistically, the MSTNDel73C mutation with FGF5 knockout mediated the activation of FOSL1 via the MEK-ERK-FOSL1 axis. The activated FOSL1 promotes skeletal muscle satellite cell proliferation and inhibits myogenic differentiation by inhibiting the expression of MyoD1, and resulting in smaller myotubes. In addition, activated ERK1/2 may inhibit the secondary fusion of myotubes by Ca2+-dependent CaMKII activation pathway, leading to myoblasts fusion to form smaller myotubes.
-
- Developmental Biology
Neuronal stem cells generate a limited and consistent number of neuronal progenies, each possessing distinct morphologies and functions, which are crucial for optimal brain function. Our study focused on a neuroblast (NB) lineage in Drosophila known as Lin A/15, which generates motoneurons (MNs) and glia. Intriguingly, Lin A/15 NB dedicates 40% of its time to producing immature MNs (iMNs) that are subsequently eliminated through apoptosis. Two RNA-binding proteins, Imp and Syp, play crucial roles in this process. Imp+ MNs survive, while Imp−, Syp+ MNs undergo apoptosis. Genetic experiments show that Imp promotes survival, whereas Syp promotes cell death in iMNs. Late-born MNs, which fail to express a functional code of transcription factors (mTFs) that control their morphological fate, are subject to elimination. Manipulating the expression of Imp and Syp in Lin A/15 NB and progeny leads to a shift of TF code in late-born MNs toward that of early-born MNs, and their survival. Additionally, introducing the TF code of early-born MNs into late-born MNs also promoted their survival. These findings demonstrate that the differential expression of Imp and Syp in iMNs links precise neuronal generation and distinct identities through the regulation of mTFs. Both Imp and Syp are conserved in vertebrates, suggesting that they play a fundamental role in precise neurogenesis across species.
