Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States
Rebecca S LaRue
University of Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, United States
Danielle N Huggins
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States
Patrice M Witschen
Comparative and Molecular Biosciences Graduate Program, University of Minnesota, Minneapolis, United States
Ayman M Ibrahim
Department of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane School of Medicine, New Orleans, United States; Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt
Andrew C Nelson
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States; Masonic Cancer Center, University of Minnesota, Minneapolis, United States
Heather L Machado
Department of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane School of Medicine, New Orleans, United States
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States; Masonic Cancer Center, University of Minnesota, Minneapolis, United States; Center for Immunology, University of Minnesota, Minneapolis, United States
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.
