Glioblastoma Cortical Organoids Recapitulate Cell-State Heterogeneity and Intercellular Transfer.

ABSTRACT: Glioblastoma (GBM) is characterized by heterogeneous malignant cells that are functionally integrated within the neuroglial microenvironment. In this study, we model this ecosystem by growing GBM into long-term cultured human cortical organoids that contain the major neuroglial cell types found in the cerebral cortex. Single-cell RNA sequencing analysis suggests that, compared with matched gliomasphere models, GBM cortical organoids more faithfully recapitulate the diversity and expression programs of malignant cell states found in patient tumors. Additionally, we observe widespread transfer of GBM transcripts and GFP to nonmalignant cells in the organoids. Mechanistically, this transfer involves extracellular vesicles and is biased toward defined GBM cell states and astroglia cell types.

SUBMITTER: Mangena V 

PROVIDER: S-EPMC11803396 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature