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Despite the clinical relevance of this behavior, the molecular underpinnings of infiltrating GBM cells in the peritumoral zone remain underexplored in patients. Here, we show that peritumoral progenitor-like GBM cells activate transcriptional programs associated with increased invasivity, synaptic activity, and NOTCH signaling. These cells spatially colocalize with neurons and exhibit an increased propensity for neuronal crosstalk. The epigenetic encoding of these infiltrative cells mirrors that of uncommitted oligodendrocyte progenitor cells (OPCs) in the developing human brain, a neurodevelopmental state marked by increased synaptic and migratory potential. Functional perturbation of a nominated regulatory factor, ZEB1, confirmed its role in maintaining the invasive and uncommitted developmental potential of infiltrative GBM cells. Our findings provide insights into the neurodevelopmental hijacking that drives GBM infiltration in patients, rationalizing further investigation into targeting differentiation potential as a therapeutic strategy.","is_dataset_classified":null,"base_score":3.258096538021482,"endowment":3.258096538021482,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40381621","pmcid":null,"openalex_id":"https://openalex.org/W4410436385","authors":[],"funders":[{"funder_name":"American Brain Tumor Association","grant_id":"ARC2300005","title":null},{"funder_name":"American Brain Tumor Association","grant_id":"DG2200052","title":null},{"funder_name":"Natural Sciences and Engineering Research Council of Canada","grant_id":"RGPIN-2023-05535","title":null},{"funder_name":"Ontario Institute for Cancer Research","grant_id":"IA-1-025","title":null},{"funder_name":"Canadian Institutes of Health Research","grant_id":"CRP 184658","title":null},{"funder_name":"Canadian Institutes of Health Research","grant_id":"PJT 185950","title":null},{"funder_name":"Cancer Research Society","grant_id":"935559","title":null},{"funder_name":"Natural Sciences and Engineering Research Council of Canada","grant_id":"unidentified","title":"unidentified"},{"funder_name":"Canada Foundation for Innovation","grant_id":"","title":null},{"funder_name":"Brain Tumour Foundation of Canada","grant_id":"","title":null},{"funder_name":"Ontario Institute for Cancer Research","grant_id":"","title":null},{"funder_name":"Princess Margaret Cancer Foundation","grant_id":"","title":null},{"funder_name":"Fondation Brain Canada","grant_id":"","title":null},{"funder_name":"Terry Fox Research Institute","grant_id":"","title":null}],"total_grants":14,"fwci":10.0545,"citation_percentile":0.98825389,"influential_citations":0,"citation_trend":[{"year":2025,"count":9},{"year":2026,"count":16}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1016/j.devcel.2025.04.022","host_type":"journal"},{"url":"https://doi.org/10.1016/j.devcel.2025.04.022","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1534580725002606?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1534580725002606?httpAccept=text/plain","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40381621","host_type":"repository"}],"fields_of_study":["Single-cell and spatial transcriptomics","Glioma Diagnosis and Treatment","Neurogenesis and neuroplasticity mechanisms","0301 basic medicine","03 medical and health sciences","Glioblastoma","Humans","Brain Neoplasms","Oligodendroglia","Animals","Zinc Finger E-box-Binding Homeobox 1","Cell Lineage","Cell Differentiation","Signal Transduction","Cell Movement","Neurons","Gene Expression Regulation, Neoplastic","Receptors, Notch","Mice","Cell Line, Tumor","Oligodendrocyte Precursor Cells","Neoplasm Invasiveness"],"mesh_terms":["Zinc Finger E-box-Binding Homeobox 1","Oligodendrocyte Precursor Cells","Animals","Brain Neoplasms","Cell Differentiation","Cell Movement","Glioblastoma","Humans","Neoplasm Invasiveness","Neurons","Oligodendroglia","Signal Transduction","Gene Expression Regulation, Neoplastic","Cell Lineage","Cell Line, Tumor","Mice","Receptors, Notch"],"keywords":["Biology","Oligodendrocyte","Glioblastoma","Lineage (genetic)","Infiltration (HVAC)","Neuroscience","Cancer research","Gene","Genetics","Central nervous system","Myelin","Invasion","Plasticity","epigenomics","Gbm","Intra-tumoral Heterogeneity","Cancer Neuroscience","Single-cell Omics","Neuron-tumor Interaction","Neurons","Oligodendrocyte Precursor Cells","Receptors, Notch","Brain Neoplasms","Zinc Finger E-box-Binding Homeobox 1","Cell Differentiation","Gene Expression Regulation, Neoplastic","Oligodendroglia","Mice","Cell Movement","Cell Line, Tumor","Humans","Animals","Cell Lineage","Neoplasm Invasiveness","Signal Transduction"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Gender equality"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T17:19:51.057453Z","pmid":null,"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":[]}