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SHR Neuro Cancer Cardio Lipid Metab Microb

Nikolova, MT; He, Z; Seimiya, M; Jonsson, G; Cao, W; Okuda, R; Wimmer, RA; Okamoto, R; Penninger, JM; Camp, JG; Treutlein, B.
Fate and state transitions during human blood vessel organoid development.
Cell. 2025; 188(12):3329-3348.e31 Doi: 10.1016/j.cell.2025.03.037
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Abstract:
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.
Find related publications in this database (using NLM MeSH Indexing)
Humans - administration & dosage
Organoids - cytology, metabolism
Animals - administration & dosage
Blood Vessels - cytology, metabolism, growth & development
Endothelial Cells - metabolism, cytology
Mice - administration & dosage
Gene Regulatory Networks - administration & dosage
Transcription Factors - metabolism
Cell Differentiation - administration & dosage
Lymphoid Enhancer-Binding Factor 1 - administration & dosage

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