ArticlebioRxiv : the preprint server for biology2025
Single-Cell Multiomic Profiling Uncovers Radiation Dosage-Sensitive, Cluster-Specific Regulatory Dynamics in Glioblastoma.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Glioblastoma (GBM) is an aggressive brain tumor that inevitably recurs after chemoradiotherapy, resulting in poor patient outcomes. Given GBM's cellular heterogeneity, we hypothesized that radiation induces sub-population specific alterations to survive and adapt to radiation stress. We performed integrated single-cell RNA-seq and ATAC-seq analyses in Glioma Stem-Like Cultures three hours after they were exposed to clinically relevant radiation doses. Radiation reshaped the cellular landscape, altering both cell type composition and GBM subtype distribution. Cluster-specific and shared transcriptional programs were induced in a dose-dependent manner, with differentially expressed genes enriching distinct biological pathways. Chromatin accessibility analyses revealed parallel cluster-specific remodeling, with both opening and closing of regulatory elements linked to functional pathway shifts. Notably, 2 Gy and 6 Gy exposures elicited conserved transcriptional profiles in RNA clusters across different radiation doses. Together, these results highlight immediate radiation-induced transcriptional and chromatin remodeling programs in GBM at single-cell resolution and identify conserved cluster-specific adaptations that may underlie therapeutic resistance.
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