Mutations affecting components of the p53 signalling pathway are collectively observed in ∼86% of all human gliomas21. Therefore, we first generated hiPSC lines from healthy/‘wild-type' human fibroblasts (hereafter referred to as WTiPSCs) and lines in where p53 was knocked down (hereafter referred to as p53KDiPSCs) (Supplementary Fig. 1a). All hiPSCs presented the typical hallmarks of pluripotency including in vivo teratoma formation in the absence of apparent malignant transformation (Supplementary Fig. 1b–f). Next, we differentiated NPCs from the generated hiPSCs (Supplementary Fig. 2a). Immunofluorescence analysis as well as multilineage differentiation potential confirmed the NPC identity of the differentiated cells (hereafter referred to as iNPCs) (Supplementary Fig. 2b–d). We have previously reported that human glioma infiltration is driven by activation of Src-family kinases (SFKs) and targeting SFKs has emerged as an attractive therapeutic approach currently under development20212223. In addition, Brennan et al.21 described mutations collectively leading to PI3K and MAPK hyperactivation in ∼90% of human gliomas. Therefore, we additionally generated iNPCs-overexpressing mutant-active versions of Src (to mimic infiltrative behaviour), EGFR (duplicated and/or mutated in ∼57% of human gliomas)21 and Ras (mutated in
