An organotypic atlas of human vascular cells
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.
Authors
- Ana-Maria Cujba (ORCID: https://orcid.org/0000-0003-3917-6751)
- Ana Raquel Maceiras (ORCID: https://orcid.org/0000-0001-7045-1331)
- Tomás Gomes (ORCID: https://orcid.org/0000-0003-1333-0191)
- Ioannis Sarropoulos (ORCID: https://orcid.org/0000-0002-2242-0562)
- Antonio M. A. Miranda (ORCID: https://orcid.org/0000-0003-4281-614X)
- Agnieska Brazovskaja (ORCID: https://orcid.org/0000-0001-7298-2072)
- Zewen Kelvin Tuong (ORCID: https://orcid.org/0000-0002-6735-6808)
- Anna M. Randi
- Chang N. Kim (ORCID: https://orcid.org/0000-0001-7921-4447)
- Catherine Tudor (ORCID: https://orcid.org/0000-0003-2093-9683)
- Sam N. Barnett (ORCID: https://orcid.org/0000-0002-8968-4319)
- Kazumasa Kanemaru (ORCID: https://orcid.org/0000-0003-0018-8966)
- Elo Madissoon (ORCID: https://orcid.org/0000-0003-2405-4911)
- Alik Huseynov (ORCID: https://orcid.org/0000-0002-1438-4389)
- James J. Cranley (ORCID: https://orcid.org/0000-0002-0408-5801)
- Tomasz J. Nowakowski (ORCID: https://orcid.org/0000-0003-2345-4964)
- Barbara Treutlein (ORCID: https://orcid.org/0000-0002-3299-5597)
- Rasheda A. Chowdhury (ORCID: https://orcid.org/0000-0003-4204-1014)
- Sarah Amalia Teichmann (ORCID: https://orcid.org/0000-0002-6294-6366)
- J. Patrick Pett (ORCID: https://orcid.org/0000-0002-5249-444X)
- Liam Bolt (ORCID: https://orcid.org/0000-0001-7293-0774)
- Robert Petryszak (ORCID: https://orcid.org/0000-0001-6333-2182)
- Shuang Li (ORCID: https://orcid.org/0000-0003-4658-9765)
- Sophie Pritchard (ORCID: https://orcid.org/0000-0001-5580-4848)
- Veronika R. Kedlian (ORCID: https://orcid.org/0000-0001-6563-0829)
- Lukáš Mach (ORCID: https://orcid.org/0000-0001-7824-4468)
- Michela Noseda (ORCID: https://orcid.org/0000-0002-9553-5029)
- Amanda J. Oliver (ORCID: https://orcid.org/0000-0003-1690-9027)
- Batuhan Çakır (ORCID: https://orcid.org/0000-0003-4513-606X)
- Rasa Elmentaite (ORCID: https://orcid.org/0000-0001-7366-5466)
- Chuan Xu (ORCID: https://orcid.org/0000-0002-6265-999X)
- Martin Prete (ORCID: https://orcid.org/0000-0002-5946-821X)
- Shani Perera (ORCID: https://orcid.org/0000-0001-8021-2078)
- Lu Yang (ORCID: https://orcid.org/0000-0002-2694-1189)
- Philomeena Daphne Joseph
- Krzysztof Polański (ORCID: https://orcid.org/0000-0002-2586-9576)
- Lia S. Campos (ORCID: https://orcid.org/0000-0001-9776-5517)
- Rebecca Toscano-Rivalta
- Michael Lee (ORCID: https://orcid.org/0000-0002-0186-4439)
- Kerstin B. Meyer (ORCID: https://orcid.org/0000-0001-5906-1498)
Institutions
- Children's Medical Research Institute (AU)
- University of California, San Francisco (US)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- University of Cambridge (GB)
- Wellcome Sanger Institute (GB)
- British Heart Foundation (GB)
- ETH Zurich (CH)
- Lung Institute (US)
- Max Planck Institute for Evolutionary Anthropology (DE)
- Chan Zuckerberg Initiative (United States) (US)
- Broad Center (US)
- Neurological Surgery (US)
- Imperial College London (GB)
Publication Details
- Journal
- Nature Medicine
- Published
- 2024-11-20
- DOI
- https://doi.org/10.1038/s41591-024-03376-x
- Citations
- 67
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 15.67
Funders
- Medical Research Council