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Barnett Sam N, Cujba Ana-Maria, Yang Lu, Maceiras Ana Raquel, Li Shuang, Kedlian Veronika R, Pett J Patrick, Polanski Krzysztof, Miranda Antonio M A, Xu Chuan, Cranley James, Kanemaru Kazumasa, Lee Michael, Mach Lukas, Perera Shani, Tudor Catherine, Joseph Philomeena D, Pritchard Sophie, Toscano-Rivalta Rebecca, Tuong Zewen K, Bolt Liam, Petryszak Robert, Prete Martin, Cakir Batuhan, Huseynov Alik, Sarropoulos Ioannis, Chowdhury Rasheda A, Elmentaite Rasa, Madissoon Elo, Oliver Amanda J, Campos Lia, Brazovskaja Agnieska, Gomes Tomás, Treutlein Barbara, Kim Chang N, Nowakowski Tomasz J, Meyer Kerstin B, Randi Anna M, Noseda Michela, Teichmann Sarah A
Аннотация
The human vascular system, comprising endothelial cells (ECs) 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. In this study, we integrated single-cell transcriptomics data from 19 human organs and tissues and defined 42 vascular cell states from approximately 67,000 cells (62 donors), including angiotypic transitional signatures along the arterial endothelial axis from large to small caliber vessels. We also characterized organotypic populations, including splenic littoral and blood-brain barrier ECs, 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 signaling. Transcription factor network analysis revealed differential regulation of downstream target genes in tissue-specific modules, such as those of FOXF1 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.