Glioblastoma (GBM) is an aggressive brain tumor marked by cellular heterogeneity, complicating treatment strategies. A study in Communications Biology employs single-nucleus RNA sequencing (snRNA-Seq) and spatial transcriptomics to profile the tumor microenvironment (TME) in the GL261-GSC syngeneic mouse model of GBM—a model that allows the study of the immune system and has been previously used to study multiple therapeutic targets. The study shows the analyses of 14 in vivo tumor samples and 5 cultured GBM cell samples, mapping cellular states across disease stages. The use of snRNA-Seq preserves sensitive cell populations, offering a more accurate representation of the TME than conventional scRNA-Seq. The study also compares snRNA-Seq with two single-cell RNA sequencing methods to assess technical biases. Treatments included temozolomide, the current standard of care, and the experimental peptide Tat-Cx43266–283, which showed significant anti-tumor effects. The findings highlight potential therapeutic targets and reveal molecular similarities between the GL261-GSC GBM model and TMEMed GBM, the most common human GBM subtype, validating its translational relevance.
Original reference: García-Vicente, L. et al. Commun. Biol. 8, 671 (2025)
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