To highlight potential differences between normal iNPCs and GTICs, we analysed the binding of SOX2, a transcription factor common to both WTiNPCs and GTICs. ChIP-seq experiments demonstrated differential binding of SOX2 in primary GTICs and transformed GTIC-like cells as compared with WTiNPCs (Fig. 3a). Correlation analysis between ChIP and mRNA expression data highlighted a total of approximately eight genes commonly regulated by SOX2 that were both differentially bound as well as differentially expressed between primary GTICs/p53KD-Ras/EGFR/SrciNPCs as compared with WTiNPCs (Supplementary Data 3, highlighted in red). In agreement with a more undifferentiated phenotype, SOX2 preferentially bound to gene promoters associated to cell dedifferentiation and neural development processes in p53KD-Ras/EGFR/SrciNPCs. Interestingly, one gene, COX6A1, a gene blocking Bax-induced apoptosis, showed decreased SOX2 binding associated with increased expression in the GTICs and p53KD-Ras/EGFR/SrciNPCs compared with the WTiNPCs and p53KDiNPCs (Fig. 3a). Genes for which decreased SOX2 binding was associated with decreased expression in GTICs and p53KD-Ras/EGFR/SrciNPCs compared with WTiNPCs and p53KDiNPCs were MAP2K5/ERK5, whose activities have been associated with tumour development and the acquisition of mesenchymal stem-like properties in cancer cells34, and C10orf67, a susceptibility locus associated with sarcoidosis and Crohn's disease (Fig. 3a).
