{"doi":"10.1101/2021.10.06.463228","title":"Patient-Derived Organoids Recapitulate Intrinsic Immune Landscapes and Progenitor Populations of Glioblastoma","abstract":"Summary Glioblastoma stem cells (GSCs) are highly self-renewing, resistant to therapy, and are able to form lethal tumors 1, 2 . Tumor organoids have been developed to study tumor evolution 1–4 , and while GSCs can form organoids for glioblastoma multiforme, our understanding of their intrinsic immune, metabolic, genetic, and molecular programs is limited. To address this, we deeply characterized GSC-derived GBM organoids using a modified protocol (GBMOsm) from several patient-derived GSCs and found they develop into complex 3D tissues with unique self-organization, cancerous metabolic states, and burdensome genetic landscapes. We discovered that GBMOsc recapitulate the presence of two important cell populations thought to drive GBM progression, SATB2 + and HOPX + progenitors. Despite being devoid of immune cells, transcriptomic analysis across GBMOsc revealed an immune-like molecular program, enriched in cytokine, antigen presentation and processing, T-cell receptor inhibitors, and interferon genes. We determined that SATB2 + and HOPX + populations contribute to this immune and interferon landscape in GBM in vivo and GBMOsm. Our work deepens our understanding of the intrinsic molecular and cellular architecture of GSC-derived GBMO and defines a novel GBMOsc intrinsic immune-like program.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":216148,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9396,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":811562,"name":"Ethan W. Hollingsworth","orcid":"0000-0002-5188-3929","position":1,"is_corresponding":false},{"id":331313,"name":"Jenna M. Bartley","orcid":"0000-0003-0302-975X","position":2,"is_corresponding":false},{"id":812022,"name":"Lauren Wisehart","orcid":null,"position":3,"is_corresponding":false},{"id":811563,"name":"Rahil Desai","orcid":"0000-0003-0605-3309","position":4,"is_corresponding":false},{"id":765367,"name":"Annalisa M. Hartlaub","orcid":null,"position":5,"is_corresponding":false},{"id":328852,"name":"Mark E. Hester","orcid":"0000-0002-3726-4128","position":6,"is_corresponding":false},{"id":334510,"name":"Paula Schiapparelli","orcid":"0000-0003-4551-6337","position":7,"is_corresponding":false},{"id":278684,"name":"Alfredo Quiñones‐Hinojosa","orcid":"0000-0003-4262-5968","position":8,"is_corresponding":false},{"id":622705,"name":"Jaime Imitola","orcid":"0000-0003-2008-3133","position":9,"is_corresponding":false},{"id":812021,"name":"Fumihiro Watanabe","orcid":null,"position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-18T23:53:00.192353Z","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":[]}