The main findings of this study are: i) SPP1 overexpression in glioma initiating cells, ii) a novel mechanism of transcriptional regulation of the SPP1 by GLI1 and OCT4, and iii) demonstration of the supportive role of tumour-derived osteopontin/SPP1 in self-renewal of glioma initiating cells. Here, SPP1 is linked to glioma.