data suggested a pathological classification as high-grade astrocytomas (grades III–IV). In line with the differences observed in vitro, in vivo analyses highlighted intergroup differences reflecting different glioma subtypes. Tumours arising from p53KDiNPCs were reminiscent of ‘small-cell' GBM, showing elongated spindle cells with eosinophilic cytoplasm alternating with clusters of compact cells with little cytoplasm and a high nuclear:cytoplasmic ratio. These tumours displayed a diffuse growth pattern but lacked the pleomorphism usually seen in GBM and no obvious transition zone to normal brain was detected. Brain tumours developed upon injection of Ras/EGFR/SrciNPCs showed a nodular growth with perivascular spread but not much diffuse parenchymal invasion was observed. Interestingly, some necrosis was observed but no pseudopalisading. Notably, the pale cytoplasm and elongated shape that were observed are reminiscent of mesenchymal morphology. Lastly, from all three groups analysed, the tumours developed after injection of p53KD-Ras/EGFR/SrciNPCs closely resembled grade IV glioblastomas. These tumours demonstrated the highest cellularity and massive necrotic areas as well as microvascularization, 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
