Molecular signature of human cerebral organoids glioma model

We have developed a cancer model of gliomas in human cerebral organoids by CRISPR/Cas9 technology to target a Harvey-Ras (H-RAS) G12V-IRES-tdTomato construct by homologous recombination into the TP53 locus. 16 weeks after electrporation, these tdTomato positive transduced cells were sorted and compared to nontransduced cellls by RNA-seq and gene expression profiles were compared to each other and with human glioma Verhaak subtype signatures. tdTomato positive and negative cell fractions of transduced organoids for four independent batches were sorted and analyzed by RNA-seq. Transcriptome data was then evaluated against the Verhaak defined glioblastoma subtypes based on clinical samples (Verhaak et al., 2011).