pseudopalisading, breaching of the pial surface and invasion of the subarachnoid space as seen in GBM and gliosarcomas. Most notably, transdifferentiated human CD31+ endothelial cells a feature of human gliomas for promoting tumour vascularization33, were only observed upon injection of p53KD-Ras/EGFR/SrciNPCs (Fig. 2d). Animals injected with WTiNPCs lived their normal lifespan and did not present brain tumours (Supplementary Table 2) whereas injection of undifferentiated iPSCs led to the formation of well-defined embryonic-like teratomas histologically distinct from the brain tumours generated upon transplantation of transformed iNPCs (Supplementary Fig. 1e). Next, we performed xenograft transplantation experiments with limited cell numbers as well as secondary tumour formation assays. Among the transformed groups, only iNPCs dysregulated for PI3K and MAPK signalling (Ras/EGFR/SrciNPCs and p53KD-Ras/EGFR/SrciNPCs) were able to form primary tumours when 500 cells were orthotopically injected into the murine brain (Supplementary Fig. 6a and Supplementary Table 3). Furthermore, serial transplantation of Ras/EGFR/SrciNPCs and p53KD-Ras/EGFR/SrciNPCs resulted in the formation of highly aggressive and infiltrative secondary tumours, presenting similar histological characteristics to those observed in the respective primary tumours, even upon secondary transplantation of 500 cells (Supplementary Fig. 6b–e and Supplementary Table 3). In agreement with the similarities between p53KDiNPCs and WTiNPCs, p53KDiNPCs did not lead
