Neoplastic and non-neoplastic astrocyte states converge on mesenchymal and injury-response programs during glioblastoma recurrence.

Reactive astrocyte-like tumor cells with mesenchymal and injury-response signatures are enriched after radiotherapy and persist in recurrent glioblastoma in a mouse model.

• Why it matters: Understanding how glioblastoma recurs after radiotherapy is crucial because the tumor microenvironment becomes supportive of tumor growth, yet the mechanisms remain poorly understood, hindering effective treatments.
• What they did: Using single-cell and spatial transcriptomics along with immunofluorescence, the study profiled healthy brain, primary tumors, and recurrences in a genetically engineered mouse model, mapping transcriptional changes across 13 non-neoplastic cell types and 10 tumor cell states.
• The result: The findings reveal that reactive astrocyte programs, shared between non-neoplastic astrocytes and tumor cells, may mediate glioblastoma radioresistance, suggesting potential targets for overcoming recurrence.