Single-Cell Transcriptome Unveils Unique Transcriptomic Signatures of Human Organ-Specific Endothelial Cells

We constructed an atlas of >210,000 ECs from 38 regions in 24 human tissues. ECs derived from different tissues show significant differences in transcriptome, phenotype, metabolism and transcriptional regulation. Arterial, venous, and lymphatic ECs shared more markers in more tissues than did capillary ECs, from which the heterogeneity of capillary ECs makes them more potential as a target for drug targeting. ECs from different tissue and vascular beds are associated with specific diseases. We found that the tissue specificity of ECs senescence is more determined by the region rather than the tissue type. Our analysis also revealed that sex differences in ECs may partly determine sex differences in brain ECs aging. The ECs atlas can be used to identify EC subclusters in single cell data of body tissues or organoids, screen tissue-specific targeted drugs, as well as provides a powerful discovery tool and resource value.