Integrated Single-Cell Transcriptomic Atlas of Human Kidney Endothelial Cells

Background: 

Kidney endothelial cells are exposed to different microenvironmental conditions that support specific physiological processes. However, the heterogeneity of human kidney endothelial cells has not yet been systematically described.

Methods: 

We reprocessed and integrated 7 datasets of human kidney control single cell/single nucleus RNA sequencing (sc/snRNAseq) 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 re-clustering identified 7 subgroups that differed in molecular characteristics and physiological functions. Mapping new data to 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 GWAS data showed a significant enrichment of endothelial cells, especially arterial endothelial cells, in terms of blood pressure heritability. Finally, we identified M1 and M12 from co-expression networks in endothelial cells that may be deeply involved in blood pressure regulation.

Conclusions: 

we created a comprehensive reference atlas of normal human kidney endothelial cells that provides the molecular foundation for understanding how the identity, function of kidney endothelial cells are altered in disease, aging, and between species. Lastly, we provide a publicly accessible online tool to explore the datasets described in this work (https://vascularmap.jiangnan.edu.cn).

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