03176nas a2200649   4500000000100000000000100001008004100002260001500043653001700058653004500075653002000120100001900140700002000159700001200179700002400191700001400215700002100229700002000250700002300270700002600293700001300319700001800332700002200350700001600372700001500388700001700403700002000420700002500440700002100465700002800486700001700514700001400531700002100545700001700566700001800583700001800601700002400619700002500643700002000668700001800688700001800706700001500724700002500739700001700764700002200781700001700803700002500820700002100845700001800866700001900884700002300903245004900926856005500975300000801030520147401038022001402512       2024                            d  c2024-11-2010aCell biology10aComputational biology and bioinformatics10aTranscriptomics1 aSam N. Barnett1 aAna-Maria Cujba1 aLu Yang1 aAna Raquel Maceiras1 aShuang Li1 aVeronika Kedlian1 aJ. Patrick Pett1 aKrzysztof Polanski1 aAntonio M. A. Miranda1 aChuan Xu1 aJames Cranley1 aKazumasa Kanemaru1 aMichael Lee1 aLukas Mach1 aShani Perera1 aCatherine Tudor1 aPhilomeena D. Joseph1 aSophie Pritchard1 aRebecca Toscano-Rivalta1 aKelvin Tuong1 aLiam Bolt1 aRobert Petryszak1 aMartin Prete1 aBatuhan Cakir1 aAlik Huseynov1 aIoannis Sarropoulos1 aRasheda A. Chowdhury1 aRasa Elmentaite1 aElo Madissoon1 aAmanda Oliver1 aLia Campos1 aAgnieska Brazovskaja1 aTomás Gomes1 aBarbara Treutlein1 aChang N. Kim1 aTomasz J. Nowakowski1 aKerstin B. Meyer1 aAnna M. Randi1 aMichela Noseda1 aSarah A. Teichmann00aAn organotypic atlas of human vascular cells  uhttps://www.nature.com/articles/s41591-024-03376-x  a1-13 aThe 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.  a1546-170X