Fate and state transitions during human blood vessel organoid development
Human blood vessel organoids (hBVOs) have emerged as a system to model human vascular development and disease. Here, we use single-cell multi-omics together with genetic and signaling pathway perturbations to reconstruct hBVO development. Mesodermal progenitors bifurcate into endothelial and mural fates in vitro, and xenografted BVOs acquire definitive arteriovenous endothelial cell specification. We infer a gene regulatory network and use single-cell genetic perturbations to identify transcription factors (TFs) and receptors involved in cell fate specification, including a role for MECOM in endothelial and mural specification. We assess the potential of BVOs to generate organotypic states, identify TFs lacking expression in hBVOs, and find that induced LEF1 overexpression increases brain vasculature specificity. Finally, we map vascular disease-associated genes to hBVO cell states and analyze an hBVO model of diabetes. Altogether, we provide a comprehensive cell state atlas of hBVO development and illuminate the power and limitation of hBVOs for translational research.
Authors
- J. Gray Camp
- Gustav Jonsson (ORCID: https://orcid.org/0000-0001-6692-8395)
- Ryo Okuda (ORCID: https://orcid.org/0000-0001-8691-7773)
- Barbara Treutlein (ORCID: https://orcid.org/0000-0002-3299-5597)
- Reiner Wimmer
- Makiko Seimiya (ORCID: https://orcid.org/0000-0001-8591-2591)
- Wuji Cao (ORCID: https://orcid.org/0000-0003-3858-4585)
- Josef Penninger (ORCID: https://orcid.org/0000-0002-8194-3777)
- Ryoko Okamoto (ORCID: https://orcid.org/0000-0003-4016-3309)
- Zhisong He (ORCID: https://orcid.org/0000-0002-1502-4801)
- Marina Nikolova (ORCID: https://orcid.org/0000-0002-8212-049X)
Institutions
- Roche (Switzerland) (CH)
- University of Basel (CH)
- ETH Zurich (CH)
- Vienna Biocenter (AT)
- Roche (Austria) (AT)
- Medical University of Vienna (AT)
Publication Details
- Journal
- Cell
- Published
- 2025-04-17
- DOI
- https://doi.org/10.1016/j.cell.2025.03.037
- Citations
- 23
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 18.54
Funders
- Silicon Valley Community Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Canada Research Chairs
- Bayerisches Staatsministerium für Bildung und Kultus, Wissenschaft und Kunst
- Innovative Medicines Initiative
- Canadian Institutes of Health Research
- European Research Council