Single cell analysis reveals deeper insight of the gateway cell type for SARS-CoV-2 in kidney

Background: Kidney injury is one of the extrapulmonary injury manifestations of COVID-19. Due to the specific expression of SARS-CoV-2 receptor angiotensinase 2 (ACE2), renal tubular epithelial cells are the main target cells of SARS-CoV-2 during kidney infection, although studies have found that the evidence of SARS-CoV-2 infection of glomerular cells. However, detailed mechanism of SARS-CoV-2 infecting kidneys still needs to be identified. Since mice don't express ACE2, humanized organoids have become important carriers for studying the mechanism of viral infection in vitro. It is still unclear whether the existing kidney organoids are suitable for studying SARS-CoV-2 virus infection. Methods: Data source: All scRNA-seq/bulk RNA-seq were downloaded from the Gene expression Omnibus. ScRNA-seq analysis: The scRNA-seq was analyzed using Seurat R package. Cell communication analysis: Cell communication was analyzed using CellPhoneDB and Cellchat R package. SCENIC analysis: Gene regulatory network was analyzed using SCENIC R package. Bulk RNA-seq analysis: We used MuSiC R package to deconvolute bulk RNA-seq data. GSEA analysis: GSEA was performed using clusterProfiler package. Results: We mined the available scRNA-seq dataset of human adult kidneys (GSE140989, GSE131882), and identified a proximal tubule subgroup, PTv cells, is susceptible to SARS-CoV-2 infection. PTv cells are highly enriched a variety of factors related to viral infections (such as ACE2, DPP4, ANPEP, CTSB, TMPRSS2 etc.). Through cell communication and gene regulatory network analysis, we inferred that PTv cells are more active than other PT cells in terms of repairment, fibrosis, development, and reabsorption. Further by analysis in the datasets of GSE139061 and GSE126805, we found that the proportion of PTv increased during acute kidney injury, suggesting that PTv could be used to predict the progression of kidney injury. Analyzing human kidney organoid scRNA-seq data (GSE109718, GSE115986, GSE108291, GSE147863, GSE119561, GSE114802, GSE136314, GSE118184), we identified that the PTv widely present in kidney organoids, indicating that kidney organoids can be used in SARS-CoV-2 related research. Conclusions: We revealed the characteristics of the PTv, a gateway cell for SARSCoV-2 in kidney, and provided a molecular basis for the feasibility of renal organoids to study the renal tropism of SARS-CoV-2.