MO365: Single-Cell Profiling Analysis Reveals the Transcriptomic Landscape Of Kidneys in Patients With Acute Kidney Injury

Abstract

Abstract BACKGROUND AND AIMS Acute kidney injury (AKI) is a common clinical syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathological mechanisms of AKI are still unclear, and specific strategies for early diagnosis and treatment of AKI are lacking. In this research, single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies of patients with AKI to elucidate novel molecular mechanisms and intercellular communications. METHOD The transcriptomes of human kidney specimens obtained from subjects with AKI and renal transplant healthy living donors were defined by scRNA-seq technology. Differentially expressed genes (DEGs) and cell clusters of the kidney were determined. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed, and cell–cell crosstalk communication analysis among distince cell subtypes were conducted. RESULTS A total of 16 distinct cell clusters were determined in kidney from subjects of AKI and control. Proximal tubule cells of AKI had up-regulation of novel pro-apoptotic genes including USP47, RASSF4, EBAG9, IER3 and NUB1, which have not been reported previously. Further, proximal tubule cells highly expressed endoplasmic reticulum stress related genes (PDIA6, ATF6, HSPA5 and DNAJC3), autophagy related genes (S100A11, CLDN1, TMBIM6, RB1CC1 and VMP1) and genes enriched in RIG-1 signaling. PALM3 was overexpressed in proximal tubule cells of AKI at both mRNA and protein levels, which is involved in cell adhesion, TLR4 signaling and infammation response. DEGs overexpressed in other tubular cells were primarily enriched in NOD-like receptor signaling, estrogen signaling, interleukin-12-mediated signaling and IL-17 signaling. Glomerular cells such as EC upregulated DEGs participating in cell adhesion, apoptosis and chemotaxis. Overexpressed genes in kidney-resident immune cells including macrophages, NK-T cells, monocytes and dendritic cells suggested abnormal regulation related with leukocyte activation, chemotaxis, cell adhesion and complement activation. In addition, the ligand-receptor interactions analysis revealed cell–cell communication contributing to adhesion, recruitment and infiltration of inflammatory cells into the kidneys, and cytokine production in the process of AKI. CONCLUSION Together, this study reveals distinct cell-specific transcriptional landscapes of kidney in AKI patients, also altered signaling pathways and potential cell-cell crosstalk in development of AKI. These data may provide new insights into the pathogenesis and potential therapeutic strategies of AKI.