{"doi":"10.64898/2025.12.01.691699","title":"Single-Cell Multiomic Profiling Uncovers Radiation Dosage-Sensitive, Cluster-Specific Regulatory Dynamics in Glioblastoma","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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":584513,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9387,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":394378,"name":"S. Weissman","orcid":null,"position":1,"is_corresponding":false},{"id":1026918,"name":"Cheol Park","orcid":"0000-0003-2371-6311","position":2,"is_corresponding":false},{"id":1497311,"name":"Maria L. G. Quiloan","orcid":"0000-0003-2075-3141","position":3,"is_corresponding":false},{"id":1497699,"name":"Blake Sun Chang","orcid":null,"position":4,"is_corresponding":false},{"id":277761,"name":"Eric C. Chang","orcid":"0000-0002-1375-5088","position":5,"is_corresponding":false},{"id":58991,"name":"Kelly Street","orcid":"0000-0001-6379-5013","position":6,"is_corresponding":false},{"id":1186994,"name":"David D. Tran","orcid":"0000-0002-2380-8921","position":7,"is_corresponding":false},{"id":304305,"name":"Aram S. Modrek","orcid":"0000-0001-7586-9833","position":8,"is_corresponding":false},{"id":1007750,"name":"Khoi Huynh","orcid":"0009-0002-5428-753X","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T02:59:11.978098Z","pmid":"41573875","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}