FC 020SINGLE CELL SEQUENCING REVEALS TRANSCRIPTIONAL SIGNATURES AND CELL CROSSTALK IN PATIENTS WITH HYPERTENSIVE NEPHROPATHY

Abstract Background and Aims Hypertensive nephropathy (HTN) is one of the leading causes of end-stage renal disease (ESRD). HTN is characterized by injury to the glomerulus, arterioles and tubulointerstitium, yet the precise mechanisms and cell-specific gene expression changes are still unknown. This study used single-cell RNA sequencing (scRNA-seq) to explore novel molecular mechanisms and the gene targets for HTN. Method The gene expression profiles of human renal biospsy samples obtained from subjects with HTN and pre-transplant healthy living controls were determined by scRNA-seq technology. Then the differentially expressed genes (DEGs) and their functions were identified. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted, and the ligand-receptor interaction among different cell populations were anlyzed. Results 18 distinct cell clusters were identified in kidney from HTN patients. Endothelial cells overexpressed LRG1, a pleiotropic factor linked to apoptosis and inflammation, which was validated at proteome level in kidney from HTN, providing a potential novel molecular target. In HTN patients, mesangial cells highly expressed proliferation related signatures (MGST1, TMSB10, EPS8 and IER2) not detected in renal diseases before. The upregualted genes in tubules of HTN were mainly participating in inflammatory signatures including IFN-γ signature, IL-17 signaling and TLR signaling. Specific gene expression of kidney-resident immune cells including dendritic cells and CD8+ T cells revealed abnormal regulation associated with cell adhesion and inflammation. Furthermore, the receptor-ligand interactions analysis indicated cell-cell crosstalks in kidney contribute to recruitment and infiltration of inflammatory cells into kidneys, and fibrotic process in hypertensive renal injury. Conclusion In brief, our data identifies distinct cell-specific gene expression profile, pathogenic signaling pathways and potential cell-cell communication in pathogenesis of HTN. These findings will provide a promising novel landscape for mechanisms and treatment of HTN.