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.

人体血管系统由内皮细胞 （EC） 和壁细胞组成，覆盖了体内广阔的表面积，在血液和组织环境之间提供了关键界面。特定血管床之间存在功能差异，但它们在组织中的分子决定因素在很大程度上仍然未知。在这里，我们整合了来自 19 个人体器官和组织的单细胞转录组学数据，并定义了来自 ~67,000 个细胞（62 个供体）的 42 种血管细胞状态，包括沿动脉内皮轴从大口径血管到小口径血管的血管型过渡特征。我们还表征了器官型群体，包括脾沿岸 ECs 和血脑屏障细胞，从而阐明了这些重要细胞状态的分子谱。询问内皮壁细胞分子串扰揭示了与 Notch、Wnt、视黄酸、前列腺素和细胞粘附信号相关的血管型和器官型通讯通路。转录因子网络分析揭示了组织特异性模块中下游靶基因的差异调控，例如 FOXF1 靶基因跨多个肺血管亚群。此外，我们对不同血管床内的血管药物靶点进行机械推断。这种开放获取资源增强了我们对人类血管细胞中血管多样性和器官型分子特征的理解，并对跨组织的血管疾病具有治疗意义。