Genetically Engineered Brain Organoids Recapitulate Spatial and Developmental States of Glioblastoma Progression [Xenium Spatial Transcriptomics]

This study develops engineered glioblastoma organoids (eGBOs) to investigate the role of specific mutations in tumor progression. The analytic framework spans single-cell analysis, spatial transcriptomics, single-cell trajectory analysis, orthotopic implantation, clinically oriented imaging, and histopathological analysis. The work provides an important proof of concept that engineered tumor organoids can model glioblastoma progression. Single-cell transcriptomes from wildtype (WT) and genetically engineered brain organoids harboring glioblastoma-associated mutations (PRO - TERTp C228T / TP53 R248Q; MES - TERTp C228T / NF1 deletion / PTEN deletion). Organoids were assessed 1 month after in vitro differentiation and 3 months after orthotopic xenotransplantation.