{"doi":"10.1101/2025.08.12.667486","title":"Mutant IDH silences GSX2 to reprogram neural progenitor cell fate and promote gliomagenesis","abstract":"Abstract Isocitrate dehydrogenase ( IDH ) mutations arise early in gliomas and are associated with a defined neurodevelopmental cancer cell hierarchy. However, how mutant IDH contributes to this hierarchy and whether this interaction promotes gliomagenesis remain unclear. We captured the dynamics of IDH-mutant glioma initiation in genetically engineered mice through time-resolved, single-cell genomics. Mutant IDH activates and induces lineage switching of neural progenitor cells (NPCs). These actions expand oligodendrocyte precursor cells, the predominant cell-of-origin for these tumors, at the expense of interneurons. Lineage switching is mediated by promoter hypermethylation and silencing of Gsx2 , a homeobox gene required for neurogenesis. Critically, Gsx2 ablation recapitulates NPC fate reprogramming by mutant IDH. We provide a new model of neural cell fate control by IDH oncogenes and insights into the developmental origins of glioma.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":558757,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"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":259417,"name":"Diana D. 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Zacharias","orcid":null,"position":10,"is_corresponding":false},{"id":817201,"name":"Zhenkang Chen","orcid":"0000-0002-7919-5546","position":11,"is_corresponding":false},{"id":1459557,"name":"Mathew Lin","orcid":"0009-0005-9297-2855","position":12,"is_corresponding":false},{"id":846400,"name":"Vinesh T. Puliyappadamba","orcid":"0000-0003-2284-4362","position":13,"is_corresponding":false},{"id":655692,"name":"Tao Chen","orcid":"0000-0002-6552-3457","position":14,"is_corresponding":false},{"id":620762,"name":"Milan R. Savani","orcid":"0000-0003-1776-451X","position":15,"is_corresponding":false},{"id":1459971,"name":"Salvador Peña","orcid":null,"position":16,"is_corresponding":false},{"id":817204,"name":"Janaka Wansapura","orcid":"0000-0003-0762-2729","position":17,"is_corresponding":false},{"id":563120,"name":"Thomas P. 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DeBerardinis","orcid":"0000-0002-2705-7432","position":27,"is_corresponding":false},{"id":2735,"name":"Itay Tirosh","orcid":"0000-0001-5477-2987","position":28,"is_corresponding":false},{"id":1409,"name":"Mario L. Suvà","orcid":"0000-0001-9898-5351","position":29,"is_corresponding":false},{"id":1454759,"name":"Lin Xu","orcid":"0000-0002-8382-2477","position":30,"is_corresponding":false},{"id":256281,"name":"Kalil G. Abdullah","orcid":"0000-0002-5662-0829","position":31,"is_corresponding":false},{"id":278608,"name":"Samuel K. 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