ArticleCell reports2017
Low-Grade Astrocytoma Mutations in IDH1, P53, and ATRX Cooperate to Block Differentiation of Human Neural Stem Cells via Repression of SOX2.
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Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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84citing papers in PubMed
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84 citing papers in PubMed, 126 citations in OpenAlex.
- A developmentally regulated long-range enhancer-promoter contact mediates human neural development.bioRxiv : the preprint server for biology · 2026Article
- Modeling pediatric brain tumors with human stem cells.Frontiers in cellular neuroscience · 2026Review
- New candidate gene mutations in astrocytoma with seizures.Scientific reports · 2025Article
- INSM1 governs a neuronal progenitor state that drives glioblastoma in a human stem cell model.Nature communications · 2025Article
- Overexpression of CCK Neuropeptide in brain is linked to ZBTB20 mutations: potential diagnostic relevance in glioblastoma.BMC medical genomics · 2025Article
- Mutations in tumor signaling, metastases, and synthetic lethality establish distinct patterns.PLoS computational biology · 2025Article
- A role for early surgical intervention in childhood low-grade glioma? Illustrative case.Journal of neurosurgery. Case lessons · 2025Article
- ATRX silences Cartpt expression in osteoblastic cells during skeletal development.The Journal of clinical investigation · 2025Article
- Exploring the Dual Roles of Neural Stem Cells in Glioblastoma: Therapeutic Implications and Opportunities.Current stem cell research & therapy · 2025Review
- Association of IDH1 Mutation and MGMT Promoter Methylation with Clinicopathological Parameters in an Ethnically Diverse Population of Adults with Gliomas in England.Biomedicines · 2024Article
- IDH inhibition in gliomas: from preclinical models to clinical trials.Nature reviews. Neurology · 2024Review
- The 2021 World Health Organization Central Nervous System Tumor Classification: The Spectrum of Diffuse Gliomas.Biomedicines · 2024Review
- Mutant IDH inhibitors induce lineage differentiation in IDH-mutant oligodendroglioma.Cancer cell · 2024Article
- Co-occurring Mutations in Different Genes Can Fuel Oncogenic Signaling and Serve as Metastatic Tumor Markers.bioRxiv : the preprint server for biology · 2024Article
- Stem cell modeling of nervous system tumors.Disease models & mechanisms · 2024Review
- A Retrospective Genomic Landscape of 661 Young Adult Glioblastomas Diagnosed Using 2016 WHO Guidelines for Central Nervous System Tumors.The oncologist · 2024Article
- Epigenetic regulation in adult neural stem cells.Frontiers in cell and developmental biology · 2024Review
- Leveraging a disulfidptosis‑related lncRNAs signature for predicting the prognosis and immunotherapy of glioma.Cancer cell international · 2023Article
- The expression profile and tumorigenic mechanisms of CD97 (ADGRE5) in glioblastoma render it a targetable vulnerability.Cell reports · 2023Article
- Exploration of cell state heterogeneity using single-cell proteomics through sensitivity-tailored data-independent acquisition.Nature communications · 2023Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 5 institutions in 1 country.
Aram S ModrekDepartment of Neurosurgery, NYU School of Medicine, New York, NY 10016, USA.
Danielle GolubDepartment of Neurosurgery, NYU School of Medicine, New York, NY 10016, USA.
Themasap KhanDepartment of Neurosurgery, NYU School of Medicine, New York, NY 10016, USA.
Devin BreadyDepartment of Neurosurgery, NYU School of Medicine, New York, NY 10016, USA.
Jod PradoDepartment of Neurosurgery, NYU School of Medicine, New York, NY 10016, USA.
Christopher BowmanDepartment of Pathology, NYU School of Medicine, New York, NY 10016, USA.
Jingjing DengDepartment of Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
Guoan ZhangDepartment of Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
Pedro P RochaDepartment of Pathology, NYU School of Medicine, New York, NY 10016, USA.
Ramya RaviramDepartment of Pathology, NYU School of Medicine, New York, NY 10016, USA.
Charalampos LazarisDepartment of Pathology, NYU School of Medicine, New York, NY 10016, USA; Applied Bioinformatics Center, NYU School of Medicine, New York, NY 10016, USA.
James M StaffordDepartment of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, NY 10016, USA.
Gary LeRoyDepartment of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, NY 10016, USA.
Michael KaderDepartment of Neurosurgery, NYU School of Medicine, New York, NY 10016, USA.
Joravar DhaliwalDepartment of Neurosurgery, NYU School of Medicine, New York, NY 10016, USA.
N Sumru BayinDepartment of Neurosurgery, NYU School of Medicine, New York, NY 10016, USA; Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
Joshua D FrensterDepartment of Neurosurgery, NYU School of Medicine, New York, NY 10016, USA; Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
Jonathan SerranoDepartment of Pathology, NYU School of Medicine, New York, NY 10016, USA.
Luis ChiribogaDepartment of Pathology, NYU School of Medicine, New York, NY 10016, USA.
Rabaa BaitalmalDepartment of Pathology, NYU School of Medicine, New York, NY 10016, USA.
Gouri NanjangudMolecular Cytogenetics Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Andrew S ChiDepartment of Neurology, NYU School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, NY 10016, USA; Brain Tumor Center, NYU School of Medicine, New York, NY 10016, USA.
John G GolfinosDepartment of Neurosurgery, NYU School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, NY 10016, USA; Brain Tumor Center, NYU School of Medicine, New York, NY 10016, USA.
Jing WangDepartment of Anesthesiology, NYU School of Medicine, New York, NY 10016, USA.
Matthias A KarajannisDepartment of Pediatrics, NYU School of Medicine, New York, NY 10016, USA; Department of Otolaryngology, NYU School of Medicine, New York, NY 10016, USA.
Richard A BonneauDepartment of Biology, New York University, New York, New York, 10003, USA; Department of Computer Science, New York University, New York, New York, 10003, USA; Simons Center for Data Analysis, New York, NY 10010, USA.
Danny ReinbergDepartment of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Aristotelis TsirigosDepartment of Pathology, NYU School of Medicine, New York, NY 10016, USA; Applied Bioinformatics Center, NYU School of Medicine, New York, NY 10016, USA.
David ZagzagDepartment of Neurosurgery, NYU School of Medicine, New York, NY 10016, USA; Department of Pathology, NYU School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, NY 10016, USA; Brain Tumor Center, NYU School of Medicine, New York, NY 10016, USA.
Matija SnuderlDepartment of Pathology, NYU School of Medicine, New York, NY 10016, USA; Department of Neurology, NYU School of Medicine, New York, NY 10016, USA; Brain Tumor Center, NYU School of Medicine, New York, NY 10016, USA.
Jane A SkokDepartment of Pathology, NYU School of Medicine, New York, NY 10016, USA.
Thomas A NeubertDepartment of Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
Dimitris G PlacantonakisDepartment of Neurosurgery, NYU School of Medicine, New York, NY 10016, USA; Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, NY 10016, USA; Brain Tumor Center, NYU School of Medicine, New York, NY 10016, USA; Neuroscience Institute, NYU School of Medicine, New York, NY 10016, USA. Electronic address: dimitris.placantonakis@nyumc.org.
New York University · USHoward Hughes Medical Institute · USMemorial Sloan Kettering Cancer Center · USNYU Langone’s Laura and Isaac Perlmutter Cancer CenterSimons Foundation · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MProject-005UL1TR001445 · NCATS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BREDELLA, MIRIAM ANTOINETTE, HOCHMAN, JUDITH S · 2015 to 2025
$103.5MVaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ADRIANA HEGUY · 1985 to 2026
$83.1MMEDICAL SCIENTIST TRAININGT32GM007308 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI PHILIPS, MARK REID · 1985 to 2019
$23.2MInstitutional Clinical and Translational Science AwardUL1TR000038 · NCATS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CRONSTEIN, BRUCE NEIL · 2012 to 2014
$16.8MTRAINING PROGRAM IN MOLECULAR ONCOLOGY &IMMUNOLOGYT32CA009161 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CARROLL, WILLIAM L., LEVY, DAVID E · 1985 to 2020
$13.3MProtein Mass Spectrometry Core Facility for NeuroscienceP30NS050276 · NINDS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI NEUBERT, THOMAS A · 2005 to 2015
$7.9MCentral glutamate signaling in postoperative pain regulation - Revision - 1R01GM115384 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Jing Wang · 2015 to 2026
$5.4MRole Of Nuclear Organization In Protecting Genome Stability During RecombinationR01GM086852 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KLUGER, YUVAL, SKOK, JANE AMANDA · 2008 to 2016
$3.8MTranscription Regulation by NC2R01GM064844 · NIGMS · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI REINBERG, DANNY · 2002 to 2014
$3.3MEnhancer Driven Gene Regulation During Lymphocyte DevelopmentR01GM112192 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI SKOK, JANE AMANDA · 2014 to 2016
$1.6MContextual Glioblastoma Screening For Efficacious Radiation SensitizersR21NS088775 · NINDS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BARCELLOS-HOFF, MARY HELEN, PLACANTONAKIS, DIMITRIS G. · 2014 to 2015
$466kNCATS NIH HHS UL1 TR000038NCATS NIH HHS UL1 TR001445NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA016087NCI NIH HHS R21 CA188968NCI NIH HHS T32 CA009161NIGMS NIH HHS K99 GM117302NIGMS NIH HHS R01 GM064844NIGMS NIH HHS R01 GM086852NIGMS NIH HHS R01 GM112192NIGMS NIH HHS R01 GM115384NIGMS NIH HHS T32 GM007308NIH HHS S10 OD018338NINDS NIH HHS P30 NS050276NINDS NIH HHS R03 NS087349NINDS NIH HHS R21 NS087241NINDS NIH HHS R21 NS088775
Abstract
Low-grade astrocytomas (LGAs) carry neomorphic mutations in isocitrate dehydrogenase (IDH) concurrently with P53 and ATRX loss. To model LGA formation, we introduced R132H IDH1, P53 shRNA, and ATRX shRNA into human neural stem cells (NSCs). These oncogenic hits blocked NSC differentiation, increased invasiveness in vivo, and led to a DNA methylation and transcriptional profile resembling IDH1 mutant human LGAs. The differentiation block was caused by transcriptional silencing of the transcription factor SOX2 secondary to disassociation of its promoter from a putative enhancer. This occurred because of reduced binding of the chromatin organizer CTCF to its DNA motifs and disrupted chromatin looping. Our human model of IDH mutant LGA formation implicates impaired NSC differentiation because of repression of SOX2 as an early driver of gliomagenesis.
Indexed as
AnimalsApoptosisAstrocytomaBrain NeoplasmsCCCTC-Binding FactorCell DifferentiationCells, CulturedDNA MethylationEpigenesis, GeneticHumansIsocitrate DehydrogenaseMiceMice, SCIDNeoplasm GradingNeoplasm InvasivenessNeural Stem CellsCCCTC-Binding FactorIsocitrate DehydrogenaseSOXB1 Transcription FactorsTumor Suppressor Protein p53X-linked Nuclear ProteinastrocytomaATRXchromatin loopingCTCFDNA methylationIDHlow-grade gliomaneural stem cellsP53SOX2
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