Description
Mononuclear phagocytes have important functions in regulating tissue injury and regeneration after AKI. We tested the hypothesis that kidney resident macrophages (R2) and infiltrative mononuclear phagocytes (R1) exist in distinct transcriptional subsets that are resolvable by single cell RNA sequencing. A further objective was to identify transcriptional signatures for those subsets. By cell sorting R2 and R1 cells from quiescent and injured mouse kidneys, we found remarkable heterogeneity among intrarenal innate immune cells. We define four subsets of dendritic cells and six subsets of R2 cells and specify differentially expressed genes that identify these cell types. Additionally, we observed subset-specific transcriptional responses to AKI. R2 cells, which express surface phenotype homogeneity, adopt distinct transcriptional programs in the steady state and after injury. Expression of MHC class II and invariant chain genes are decreased in a predominant subset of R2 cells after AKI. In contrast, other macrophage lineage-defining genes such as C1qa, b, and c, are expressed at similar levels across R2 cell subsets and their expression does not change in response to injury. This study has allowed us to identify R2 and R1 subsets that may prove to be therapeutic targets for inhibiting damaging inflammation and fibrosis or promoting tissue regeneration.
Overall Design
Mice subjected to renal ischemia reperfusion injury or left untreated: Renal leukocytes isolated and sorted by FACS to F4/80Hi/CD11bLo and F4/80Int/CD11bHi. However, how sorts were done depended on sample (see sample list)
Curator
xm_li