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

Ying Wang, Thomas S. Chaffee, Rebecca S. Larue, Danielle N. Huggins, Patrice M. Witschen, Ayman M. Ibrahim, Andrew C. Nelson, Heather L. Machado, Kathryn L. Schwertfeger

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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. Macrophages have been linked to ductal development in the virgin mammary gland, but 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 that is characterized by the 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.

Original languageEnglish (US)
Article numbere57438
Pages (from-to)1-27
Number of pages27
StatePublished - Jun 2020

Bibliographical note

Funding Information:
The authors thank Dr Yi Shan (Xuanwu Hospital, Capital Medical University) for generating the mouse schematic and Ms Bobbie Daughters for her invaluable work to secure the IRB approval and to acquire the human tissue samples used in this study. The authors would also like to acknowledge the technical help provided by the University of Minnesota Imaging Core (UIC), University of Minnesota Genomics Core and Dr Kejing Song at the Tulane Center for Translational Research in Infection and Immunity NextGen Sequencing Core. This work was supported by a T32 fellowship (OD010993) to PMW; American Cancer Society Post-doctoral Fellowship (#132570-PF-18-140-01-CSM) to DNH; American Cancer Society Clinical Scholar Development Grant (#132574-CSDG-18-139-01-CSM) to ACN; NIH R01CA212518 to HLM; and NIH funding R01CA215052, R01HD095858 and R21CA235385 to KLS.

Publisher Copyright:
© Wang et al.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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