Single-Cell RNA Sequencing Identifies Candidate Renal Resident Macrophage Gene Expression Signatures across Species

• Published in: Journal of the American Society of Nephrology Vol. 30; no. 5; pp. 767 - 781
• Main Authors: Zimmerman, Kurt A, Bentley, Melissa R, Lever, Jeremie M, Li, Zhang, Crossman, David K, Song, Cheng Jack, Liu, Shanrun, Crowley, Michael R, George, James F, Mrug, Michal, Yoder, Bradley K
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 01.05.2019
• Subjects: Analysis of Variance; Animals; Antigens, Differentiation, B-Lymphocyte - immunology; Basic Research; Biomarkers - metabolism; Cells, Cultured; Flow Cytometry; Gene Expression Regulation; Histocompatibility Antigens Class II - immunology; Humans; Immunity, Innate - genetics; Intercellular Adhesion Molecule-1 - immunology; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; Models, Animal; Parabiosis; Rats; Rats, Sprague-Dawley; Sequence Analysis, RNA; Species Specificity; transcriptional profiling; immunology; macrophages
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/asn.2018090931

Resident macrophages regulate homeostatic and disease processes in multiple tissues, including the kidney. Despite having well defined markers to identify these cells in mice, technical limitations have prevented identification of a similar cell type across species. The inability to identify resident macrophage populations across species hinders the translation of data obtained from animal model to human patients. As an entry point to determine novel markers that could identify resident macrophages across species, we performed single-cell RNA sequencing (scRNAseq) analysis of all T and B cell-negative CD45 innate immune cells in mouse, rat, pig, and human kidney tissue. We identified genes with enriched expression in mouse renal resident macrophages that were also present in candidate resident macrophage populations across species. Using the scRNAseq data, we defined a novel set of possible cell surface markers (Cd74 and Cd81) for these candidate kidney resident macrophages. We confirmed, using parabiosis and flow cytometry, that these proteins are indeed enriched in mouse resident macrophages. Flow cytometry data also indicated the existence of a defined population of innate immune cells in rat and human kidney tissue that coexpress CD74 and CD81, suggesting the presence of renal resident macrophages in multiple species. Based on transcriptional signatures, our data indicate that there is a conserved population of innate immune cells across multiple species that have been defined as resident macrophages in the mouse. Further, we identified potential cell surface markers to allow for future identification and characterization of this candidate resident macrophage population in mouse, rat, and pig translational studies.