The cell of origin for malignant brain tumors remains uncertain, but de-differentiation from mature cells in the CNS has always been considered a strong possibility. In this issue of Nature Neuroscience, Alcantara Llaguno and colleagues report that differentiated neurons resist transformation by glioblastoma-associated mutations, pointing to neural stem cells or immature progenitors as the most likely cells of origin for these tumors, rather than cells of a relatively mature neuronal lineage.
