Single-Cell Multiomic Profiling Uncovers Radiation Dosage-Sensitive, Cluster-Specific Regulatory Dynamics in...

Area of Science:

• Oncology
• Genomics
• Neuroscience

Background:

• Glioblastoma (GBM) is an aggressive brain tumor with poor outcomes after standard treatment.
• Tumor recurrence is linked to cellular heterogeneity and adaptive responses to therapy.

Purpose of the Study:

• To investigate the immediate, single-cell responses of GBM to radiation.
• To understand how radiation stress induces adaptive survival mechanisms in specific GBM cell populations.

Main Methods:

• Integrated single-cell RNA sequencing (scRNA-seq) and ATAC sequencing (scATAC-seq) were performed on Glioma Stem-Like Cultures.
• Cells were exposed to clinically relevant radiation doses (2 Gy and 6 Gy).
• Analysis focused on transcriptional and chromatin accessibility changes three hours post-irradiation.

Main Results:

• Radiation exposure significantly altered GBM cell type composition and subtype distribution.
• Dose-dependent transcriptional programs and chromatin remodeling were observed in a cluster-specific manner.
• Conserved transcriptional profiles were identified across different radiation doses, suggesting robust adaptive responses.

Conclusions:

• Immediate, single-cell resolution reveals radiation-induced transcriptional and chromatin remodeling in GBM.
• Cluster-specific adaptations in response to radiation may contribute to glioblastoma's therapeutic resistance.
• Understanding these rapid adaptive mechanisms is crucial for developing more effective GBM treatments.