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Abstract: SA-PO409

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

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Zimmerman, Kurt, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Li, Zhang, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • George, James F., University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Mrug, Michal, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Yoder, Bradley K., University of Alabama at Birmingham, Birmingham, Alabama, United States
Background

Resident macrophages are involved in homeostatic and disease processes in multiple tissues including the kidney. Despite the use of well-defined markers to identify these cells in mice, technical limitations have prevented the identification of a similar cell type across species.

Methods

As an entry point to determine novel markers that could identify resident macrophages across species, we performed single cell RNA sequencing (scRNAseq) analysis of CD45+ innate immune cells in mouse, rat, pig and human kidney tissue.

Results

Using this approach, we identified multiple genes whose expression is enriched in mouse renal resident macrophages and in candidate resident macrophage populations across species. Further, we identified a novel set of possible cell-surface markers for these candidate kidney resident macrophages (Cd74, Cd81) and confirm using parabiosis and flow cytometry approaches that these proteins are indeed enriched in mouse resident macrophages. Our flow cytometry data also indicate there is a defined population of innate immune cells in rat and human kidney tissue that co-express CD74 and CD81, suggesting the presence of renal resident macrophages in multiple species. Finally, we show that we can use these novel resident macrophage markers to identify a population of cells that is independent of peripheral blood input in the rat.

Conclusion

Collectively, our data indicate that, based on transcriptional signatures, there is a conserved population of innate immune cells across multiple species that have been defined as resident macrophages in the mouse. In addition, we provide a proof of principle experiment showing that we can use our novel markers to identify a population of CD45+ innate immune cells that are independent of peripheral blood input in the rat.

Funding

  • NIDDK Support