Integrated Single-Cell Transcriptomic Atlas of Human Kidney Endothelial Cells

Key Points We created a comprehensive reference atlas of normal human kidney endothelial cells. We confirmed that endothelial cell types in the human kidney were also highly conserved in the mouse kidney. Background Kidney endothelial cells are exposed to different microenvironmental conditions that support specific physiologic processes. However, the heterogeneity of human kidney endothelial cells has not yet been systematically described. Methods We reprocessed and integrated seven human kidney control single-cell/single-nucleus RNA sequencing datasets of >200,000 kidney cells in the same process. Results We identified five major cell types, 29,992 of which were endothelial cells. Endothelial cell reclustering identified seven subgroups that differed in molecular characteristics and physiologic functions. Mapping new data to a normal kidney endothelial cell atlas allows rapid data annotation and analysis. We confirmed that endothelial cell types in the human kidney were also highly conserved in the mouse kidney and identified endothelial marker genes that were conserved in humans and mice, as well as differentially expressed genes between corresponding subpopulations. Furthermore, combined analysis of single-cell transcriptome data with public genome-wide association study data showed a significant enrichment of endothelial cells, especially arterial endothelial cells, in BP heritability. Finally, we identified M1 and M12 from coexpression networks in endothelial cells that may be deeply involved in BP regulation. Conclusions We created a comprehensive reference atlas of normal human kidney endothelial cells that provides the molecular foundation for understanding how the identity and function of kidney endothelial cells are altered in disease, aging, and between species. Finally, we provide a publicly accessible online tool to explore the datasets described in this work (https://vascularmap.jiangnan.edu.cn).