TY - JOUR
KW - Cell biology
KW - Computational biology and bioinformatics
KW - Transcriptomics
AU - Sam N. Barnett
AU - Ana-Maria Cujba
AU - Lu Yang
AU - Ana Raquel Maceiras
AU - Shuang Li
AU - Veronika Kedlian
AU - J. Patrick Pett
AU - Krzysztof Polanski
AU - Antonio M. A. Miranda
AU - Chuan Xu
AU - James Cranley
AU - Kazumasa Kanemaru
AU - Michael Lee
AU - Lukas Mach
AU - Shani Perera
AU - Catherine Tudor
AU - Philomeena D. Joseph
AU - Sophie Pritchard
AU - Rebecca Toscano-Rivalta
AU - Kelvin Tuong
AU - Liam Bolt
AU - Robert Petryszak
AU - Martin Prete
AU - Batuhan Cakir
AU - Alik Huseynov
AU - Ioannis Sarropoulos
AU - Rasheda A. Chowdhury
AU - Rasa Elmentaite
AU - Elo Madissoon
AU - Amanda Oliver
AU - Lia Campos
AU - Agnieska Brazovskaja
AU - Tomás Gomes
AU - Barbara Treutlein
AU - Chang N. Kim
AU - Tomasz J. Nowakowski
AU - Kerstin B. Meyer
AU - Anna M. Randi
AU - Michela Noseda
AU - Sarah A. Teichmann
AB - 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.
BT - Nature Medicine
DA - 2024-11-20
DO - 10.1038/s41591-024-03376-x
LA - en
N2 - 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.
PY - 2024
SP - 1
EP - 1
T2 - Nature Medicine
TI - An organotypic atlas of human vascular cells
UR - https://www.nature.com/articles/s41591-024-03376-x
Y2 - 2024-11-26
SN - 1546-170X
ER -