Glioblastoma (GBM) is the most frequent and most aggressive primary brain tumor with low survival rates despite decades of intensive research. Patient-derived GBM cells are used here to study their invasion into and their interaction with human cerebral organoids. Confocal microscopy and single-cell RNA sequencing are used for the analysis. It was shown that tumor cells extend a network of long microtubes within the normal organoids, recapitulating the in vivo behaviour as this tumor aggressively infiltrates the brain via microtubes. A transcriptional program was identified induced by the interactions between normal brain cells and tumor cells, which upregulates genes required for tumor dispersion. Hence, the model is useful for studying GBM invasion and transcriptional heterogeneity in vitro, with applications for both pharmacological screens and patient-specific treatment selection.
Modeling glioblastoma invasion using human brain organoids and single-cell transcriptomics
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