Glioblastoma's malignant states are not scattered at random: a developmental-to-injury-and-hypoxia trajectory layers around the necrotic core
Glioblastoma malignant states were treated as parallel subtypes, and a single biopsy could not represent the whole tumour. Pairing single-nucleus and spatial transcriptomics across 12 IDH-wild-type primary tumours and 57 sampling sites revealed a trajectory from developmental-like states toward glial injury response and hypoxia, layered in space from the infiltrating edge to the necrotic core; the trajectory appears across tumour subtypes and genetically distinct subclones and is recapitulated in patient-derived organoids.