The origins of gliomas are not well understood. Here, oncogenic lentiviral vectors targeting the genes that encode tumour protein 53 (also known as p53) and neurofibromatosis type 1 (which are often mutated in gliomas) were used to transduce stem cells, astrocytes and mature neurons in mouse brains. Transduced cells from all cell populations — not just stem cells, as might have been expected — produced malignant gliomas with high expression of stem cell markers and low expression of markers of differentiated cells. Thus, gliomas can arise by dedifferentiation of mature neurons and astrocytes.