Single-Cell Transcriptome Profiling Reveals a Distinct Immune Cell Population in the Glomerulus of Hypertensive Kidneys

Previous studies demonstrated a pro-hypertensive role for innate and adaptive immune mechanisms in Dahl Salt Sensitive (SS) rats. Consistent with earlier reports, initial experiments in this study demonstrated a significant 2-2.8-fold increase in total CD45+ leukocytes, CD11b/c+ myeloid cells, CD3+ T cells, and CD45R+ B cells in the kidney of Dahl SS fed 4.0% NaCl compared to rats fed 0.4% NaCl (n=8-12/group). To further characterize these immune cell populations, high-resolution transcriptomic profiling was performed on Dahl SS kidneys dissociated into a single cell suspension and subjected to single-cell RNA sequencing. Following normalization, unsupervised clustering identified 12 distinct clusters of relevant renal cell types. Interestingly, three distinct clusters of cells expressing Ptprc, the gene encoding CD45, were identified. The largest Ptprc+ cluster predominantly expressed macrophage-specific genes, the second cluster expressed lymphocyte-related genes, and the final cluster expressed monocyte-specific transcripts. Hierarchical subclustering was next performed to identify distinct subpopulations with unique transcriptional profiles. Of interest, this approach revealed seven distinct subclusters within the Ptprb+ glomerular cluster. A pivotal finding was the identification of a distinct glomerulus-associated Ptprc+ immune cell cluster, which also exhibited Ptprb transcript expression. The intraglomerular immune cell population exhibits a molecular signature distinct from that of extraglomerular myeloid and lymphocyte cell populations, suggesting a specialized role within the glomerulus. A Venn analysis comparing the immune subcluster with other immune clusters, demonstrated that approximately one-third of the genes were shared between the intraglomerular immune subpopulation and the extraglomerular immune clusters, indicating some level of overlap in their molecular profiles. However, we specifically prioritized genes uniquely expressed within the immune subcluster for comprehensive downstream pathway analysis. This targeted analysis revealed significant enrichment of pathways associated with Toll-like receptor (TLR) signaling, suggesting its potential as a key mediator of the distinct immune responses observed within the glomerulus. HL161231, HL166458 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.