An organotypic atlas of human vascular cells.

Abstract

The human vascular system, comprising endothelial (EC) and mural cells, covers a vast surface area in the body, providing a critical interface between blood and tissue environments. Functional differences exist across specific vascular beds, but their molecular determinants across tissues remain largely unknown. Here, we integrated single-cell transcriptomics data from 19 human organs and tissues, and defined 42 vascular cell states from ~67,000 cells (62 donors), including angiotypic transitional signatures along the arterial endothelial axis from large to small calibre vessels. We also characterised organotypic populations, including splenic littoral ECs and blood-brain barrier cells, thus clarifying the molecular profiles of these important cell states. Interrogating endothelial-mural cell molecular crosstalk revealed angiotypic and organotypic communication pathways related to Notch, Wnt, retinoic acid, prostaglandin, and cell adhesion signalling. Transcription factor network analysis revealed differential regulation of downstream target genes in tissue-specific modules, such as FOXF1 target genes across multiple lung vascular subpopulations. Additionally, we make mechanistic inferences of vascular drug targets within different vascular beds. This open access resource enhances our understanding of angiodiversity and organotypic molecular signatures in human vascular cells and has therapeutic implications for vascular diseases across tissues.