Human vascular organoids with a mosaic AKT1 mutation recapitulate Proteus syndrome.

ABSTRACT: Vascular malformation, a key clinical phenotype of Proteus syndrome, lacks effective models for pathophysiological study and drug development due to limited patient sample access. To bridge this gap, we built a human vascular organoid model replicating Proteus syndrome's vasculature. Using CRISPR/Cas9 genome editing and gene overexpression, we created induced pluripotent stem cells (iPSCs) embodying the Proteus syndrome-specific AKT^E17K point mutation for organoid generation. Our findings revealed that AKT overactivation in these organoids resulted in smaller sizes yet increased vascular connectivity, although with less stable connections. This could be due to the significant vasculogenesis induced by AKT overactivation. This phenomenon likely stems from boosted vasculogenesis t

SUBMITTER: He S 

PROVIDER: S-EPMC10849631 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature