Distinct Subpopulations of Mouse and Human Kidney Resident Macrophages in Acute Kidney Injury

Abstract

Abstract Introduction Kidney resident macrophages (KRMs) are important in renal homeostasis and the response to acute kidney injury. Preliminary data suggests that the KRM population consists of several undescribed subpopulations. Here, we combined single-cell RNA sequencing (scRNAseq) and spatial transcriptomics to identify and localize KRM subpopulations during homeostasis and injury. Methods KRMs were isolated from C57BL/6J mice without treatment and after bilateral ischemia-reperfusion injury (BIRI) as well as from a human donor kidney. ScRNAseq was performed using the 10X Genomics Chromium platform and spatial transcriptomics using the 10X Visium platform. Gene expression data were integrated and analyzed using the R package, Seurat 4.0. Results UMAP plots of integrated data revealed seven major clusters of mouse KRMs with unique transcriptional profiles associated with distinct functions. Spatial transcriptomics revealed that these clusters reside in distinct cellular compartments within the kidney and appear to associate with specific renal structures. Following BIRI, these subpopulations appear in cellular compartments distinct from those occupied in the controls. Several human KRM clusters were correlated with those of the mouse and localized to specific regions of the kidney. Conclusion Transcriptionally distinct subpopulations of mouse KRMs reside within specific kidney microenvironments and change location as a function of injury. Similar subpopulations of KRMs were identified in the human kidney as well. Therefore, further study of the temporal and spatial characteristics and signaling pathways of these subpopulations in the context of homeostasis and injury is warranted. Supported by grants from NIH (R01-DK-59600, T32-AI007051)