{"doi":"10.1101/2024.04.24.590852","title":"Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma","abstract":"Abstract The sub-ventricular zone (SVZ) is the most well-characterized neurogenic area in the mammalian brain. We previously showed that in 65% of patients with glioblastoma (GBM), the SVZ is a reservoir of cancer stem-like cells that contribute to treatment resistance and emergence of recurrence. Here, we built a single-nucleus RNA-sequencing-based microenvironment landscape of the tumor mass (T_Mass) and the SVZ (T_SVZ) of 15 GBM patients and 2 histologically normal SVZ (N_SVZ) samples as controls. We identified a mesenchymal signature in the T_SVZ of GBM patients: tumor cells from the T_SVZ relied on the ZEB1 regulatory network, whereas tumor cells in the T_Mass relied on the TEAD1 regulatory network. Moreover, the T_SVZ microenvironment was predominantly characterized by tumor-supportive microglia, which spatially co-exist and establish heterotypic interactions with tumor cells. Lastly, differential gene expression analyses, predictions of ligand-receptor and incoming/outgoing interactions, and functional assays revealed that the IL-1β/IL-1RAcP and Wnt-5a/Frizzled-3 pathways are therapeutic targets in the T_SVZ microenvironment. Our data provide insights into the biology of the SVZ in GBM patients and identify specific targets of this microenvironment.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":488409,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7529,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":68594,"name":"Vanesa S. Fernandez Avalos","orcid":null,"position":1,"is_corresponding":false},{"id":1207244,"name":"Suganya Subramanian","orcid":"0009-0007-2822-9420","position":2,"is_corresponding":false},{"id":1333448,"name":"B Granger","orcid":null,"position":3,"is_corresponding":false},{"id":137545,"name":"F Martinez","orcid":null,"position":4,"is_corresponding":false},{"id":84191,"name":"Silvia Varela","orcid":"0000-0002-1865-3291","position":5,"is_corresponding":false},{"id":1333111,"name":"Drew Moore","orcid":"0009-0005-0926-0874","position":6,"is_corresponding":false},{"id":1087182,"name":"Eddie Perkins","orcid":null,"position":7,"is_corresponding":false},{"id":1333112,"name":"М. И. Коган","orcid":"0000-0002-1710-0169","position":8,"is_corresponding":false},{"id":311328,"name":"Stefano Berto","orcid":"0000-0001-9028-9458","position":9,"is_corresponding":false},{"id":1141546,"name":"Muhammad Omar Chohan","orcid":"0000-0003-4542-4651","position":10,"is_corresponding":false},{"id":1221734,"name":"Christian A. Bowers","orcid":"0000-0001-6299-503X","position":11,"is_corresponding":false},{"id":288256,"name":"Sara Piccirillo","orcid":"0000-0003-4109-1992","position":12,"is_corresponding":false},{"id":516428,"name":"Yamhilette Licón-Muñoz","orcid":"0000-0002-6034-9058","position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":null,"created_at":"2026-07-19T02:08:19.655720Z","pmid":"38712234","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":[]}