PRNP and glioblastoma: In this study, we show that the reduction of the expression of PrPC in GBM CSCs: (a) decreases cell proliferation rate; (b) dramatically reduces self-renewal (as evaluated by spherogenesis activity) and clonogenic activities; (c) promotes spontaneous cell differentiation, characterized by down-regulation of specific stem cell markers involved in pluripotency and self-renewal, and inducing morphological and phenotypical (i.e. expression of GFAP) features of mature astrocytes.