Fate and State Transitions during Human Blood Vessel Organoid Development: Perturbation

Human blood vessel organoids (hBVOs) have emerged as a system to model human vascular development and disease. Here, we use genetic and signaling pathway perturbations to reconstruct hBVO development. We 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, particularly brain vasculature-specificity, using small-molecule and TF-gene over expression perturbation. Finally, we mimic inflammatory and diabetic conditions in hBVOs in vitro. Altogether, we provide data for the first comprehensive cell state atlas of hBVO development and illuminate the power and limitation of hBVOs for translational research.