第63回(令和2年度)日本腎臓学会学術総会にてBest Poster Award を受賞しました。

平成20年卒　腎臓内科　病院助教の桐田雄平先生が第63回(令和2年度)日本腎臓学会学術総会にてBest Poster Award を受賞しました。

Single cell profiling of acute kidney injury reveals conserved cellular responses to injury

Background: After acute kidney injury(AKI), patients either recover or alternatively develop fibrosis and chronic kidney disease(CKD). To better define the cellular and molecular mechanisms of AKI and the AKI to CKD transition, we performed comprehensive single nucleus RNA-seq(snRNA-seq)on both mouse and human AKI. Methods: We generated 126,578 single-nucleus transcriptomes from mouse kidney after IRI:4 hours, 12 hours, 2 days, 14 days, 6 weeks and sham(n=3 for each), and 38,189 nuclei from a healthy and AKI adult human kidney using the 10X platform and performed a comprehensive informatic analysis and gene expression validation. Results: We define transcriptional states that distinguish proximal tubule destined for successful vs. failed repair. Using receptor-ligand analysis, we identify and define pro-fibrotic and pro-inflammatory signals secreted by failed repair epithelia to fibroblasts, endothelial cells and leukocytes, driving the AKI to CKD transition. We show that a scattered cell population in human healthy kidney exists that recapitulates the epithelial repair signature and that likely represents the cell type that prior reports characterized as a fixed stem cell population. Conclusion:The first comprehensive snRNA-seq atlas of mouse and human AKI kidney reveals that a distinct failed repair proximal tubule cell state drives fibrosis after injury, describes dynamic intercellular communication networks and identifies conserved transcriptional pathways shared between murine models and human AKI. Our study provides a detailed overview of conserved immune and parenchymal cell states and interactions that determine whether kidney repair is successful or leads to chronic fibrosis.