Heterogeneous origins and functions of mouse skeletal muscle-resident macrophages

• Published in: Proceedings of the National Academy of Sciences - PNAS 2020-08, Vol.117 (34), p.20729-20740
• Main Authors: Wang, Xingyu, Sathe, Adwait Amod, Smith, Gregory R., Ruf-Zamojski, Frederique, Nair, Venugopalan, Lavine, Kory J., Xing, Chao, Sealfon, Stuart C., Zhou, Lan
• Format: Article
• Language: English
• Subjects: Animals; Biological activity; Biological Sciences; Bone marrow; Bone Marrow - metabolism; Bone marrow transplantation; Bone Marrow Transplantation - methods; Cell Differentiation - genetics; Cell Lineage - genetics; Embryonic Development; Embryos; Female; Fetuses; Gene expression; Genetic Heterogeneity; Hematopoiesis; Hematopoiesis - genetics; Hematopoietic stem cells; Hematopoietic Stem Cells - metabolism; Homeostasis; Immune response; Macrophages; Macrophages - immunology; Macrophages - metabolism; Macrophages - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocytes - immunology; Monocytes - metabolism; Muscle, Skeletal - immunology; Muscles; Musculoskeletal system; Ontogeny; Organogenesis; Organogenesis - genetics; Origins; Regeneration; Skeletal muscle; Stem cell transplantation; Stem cells; Tissues; Transcription factors; Yolk; Yolk sac
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1915950117

Tissue-resident macrophages can originate from embryonic or adult hematopoiesis. They play important roles in a wide range of biological processes including tissue remodeling during organogenesis, organ homeostasis, repair following injury, and immune response to pathogens. Although the origins and tissue-specific functions of resident macrophages have been extensively studied in many other tissues, they are not well characterized in skeletal muscle. In the present study, we have characterized the ontogeny of skeletal muscle-resident macrophages by lineage tracing and bone marrow transplant experiments. We demonstrate that skeletal muscle-resident macrophages originate from both embryonic hematopoietic progenitors located within the yolk sac and fetal liver as well as definitive hematopoietic stem cells located within the bone marrow of adultmice. Single-cell-based transcriptome analyses revealed that skeletal muscle-resident macrophages are distinctive from resident macrophages in other tissues as they express a distinct complement of transcription factors and are composed of functionally diverse subsets correlating to their origins. Functionally, skeletal muscleresident macrophages appear to maintain tissue homeostasis and promote muscle growth and regeneration.