Integrative Single-Cell RNA and ATAC Sequencing Uncovers Dosage-Sensitive, Cluster-Specific Regulatory Dynamics in Glioblastoma

ABSTRACT: Glioblastoma (GBM) is an aggressive brain tumor that inevitably recurs after radiation therapy, 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 across multiple GBM models 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 independent GBM lines. Together, these results highlight radiation-induced transcriptional and chromatin remodeling programs in GBM at single-cell resolution and identify conserved cluster-specific adaptations that may underlie therapeutic resistance.

ORGANISM(S): Homo sapiens

PROVIDER: GSE309579 | GEO | 2026/02/16

REPOSITORIES: GEO