Genetically Engineered Brain Organoids Recapitulate Spatial and Developmental States of Glioblastoma Progression.

ABSTRACT: Glioblastoma (GBM) is an aggressive form of brain cancer that is highly resistant to therapy due to significant intra-tumoral heterogeneity. The lack of robust in vitro models to study early tumor progression has hindered the development of effective therapies. Here, this study develops engineered GBM organoids (eGBOs) harboring GBM subtype-specific oncogenic mutations to investigate the underlying transcriptional regulation of tumor progression. Single-cell and spatial transcriptomic analyses revealed that these mutations disrupt normal neurodevelopment gene regulatory networks resulting in changes in cellular composition and spatial organization. Upon xenotransplantation into immunodeficient mice, eGBOs form tumors that recapitulate the transcriptional and spatial landscape of human GBM

SUBMITTER: Ishahak M 

PROVIDER: S-EPMC11905097 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature