ArticleGlia2022
A novel mouse model of diffuse midline glioma initiated in neonatal oligodendrocyte progenitor cells highlights cell-of-origin dependent effects of H3K27M.
Article in Glia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- Oncohistone inhibition reshapes tumor-microenvironment communication in Diffuse Midline Glioma (DMG).bioRxiv : the preprint server for biology · 2026Article
- Prevalence and Clinicoradiopathological Characterization of H3 K27-Altered Diffuse Midline Gliomas in Adults-A Retrospective Observational Study.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Article
- The Gut-Brain-Immune Axis in Glioma: Emerging Mechanisms and Therapeutic Opportunities.Cellular and molecular neurobiology · 2026Review
- Modeling diffuse midline glioma through triple-electrode in utero electroporation of the developing mouse pons.PloS one · 2026Article
- The Bermuda Triangle of paediatric brain cancers: epigenetics, developmental timing window and cell of origin.Cancer metastasis reviews · 2025Review
- Single-Cell Profiling of Pediatric High-Grade Gliomas Reveals OPC-Like Subpopulations Driving Tumorigenic Lineage Transitions.Pediatric discovery · 2025Article
- Implications of canonical histone H3.1 and histone variant H3.3 in cancer.Open biology · 2025Review
- Article
- Combining the RCAS/tv-a retrovirus and CRISPR/Cas9 gene editing systems to generate primary mouse models of diffuse midline glioma.Neoplasia (New York, N.Y.) · 2025Article
- Effects of combination therapy of a CDK4/6 and MEK inhibitor in diffuse midline glioma preclinical models.PloS one · 2025Article
- Epigenetic modifications and their roles in pediatric brain tumor formation: emerging insights from chromatin dysregulation.Frontiers in oncology · 2025Review
- The Landscape of Pediatric High-Grade Gliomas: The Virtues and Pitfalls of Pre-Clinical Models.Biology · 2024Review
- Pediatric Diffuse Midline Glioma H3K27-Altered: From Developmental Origins to Therapeutic Challenges.Cancers · 2024Review
- Diffuse hemispheric glioma with H3 p.K28M (K27M) mutation: Unusual non-midline presentation of diffuse midline glioma, H3 K27M-altered?Journal of neuropathology and experimental neurology · 2024Article
- Stem cell modeling of nervous system tumors.Disease models & mechanisms · 2024Review
- Therapeutically targeting the unique disease landscape of pediatric high-grade gliomas.Frontiers in oncology · 2024Review
- Oncohistones and disrupted development in pediatric-type diffuse high-grade glioma.Cancer metastasis reviews · 2023Review
- Ganglioglioma deep transcriptomics reveals primitive neuroectoderm neural precursor-like population.Acta neuropathologica communications · 2023Article
- Applying single cell multi-omic analyses to understand treatment resistance in pediatric high grade glioma.Frontiers in pharmacology · 2023Review
- The Effect ofCancers · 2022Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Diffuse midline glioma (DMG) is a type of lethal brain tumor that develops mainly in children. The majority of DMG harbor the K27M mutation in histone H3. Oligodendrocyte progenitor cells (OPCs) in the brainstem are candidate cells-of-origin for DMG, yet there is no genetically engineered mouse model of DMG initiated in OPCs. Here, we used the RCAS/Tv-a avian retroviral system to generate DMG in Olig2-expressing progenitors and Nestin-expressing progenitors in the neonatal mouse brainstem. PDGF-A or PDGF-B overexpression, along with p53 deletion, resulted in gliomas in both models. Exogenous overexpression of H3.3K27M had a significant effect on tumor latency and tumor cell proliferation when compared with H3.3WT in Nestin+ cells but not in Olig2+ cells. Further, the fraction of H3.3K27M-positive cells was significantly lower in DMGs initiated in Olig2+ cells relative to Nestin+ cells, both in PDGF-A and PDGF-B-driven models, suggesting that the requirement for H3.3K27M is reduced when tumorigenesis is initiated in Olig2+ cells. RNA-sequencing analysis revealed that the differentially expressed genes in H3.3K27M tumors were non-overlapping between Olig2;PDGF-B, Olig2;PDGF-A, and Nestin;PDGF-A models. GSEA analysis of PDGFA tumors confirmed that the transcriptomal effects of H3.3K27M are cell-of-origin dependent with H3.3K27M promoting epithelial-to-mesenchymal transition (EMT) and angiogenesis when Olig2 marks the cell-of-origin and inhibiting EMT and angiogenesis when Nestin marks the cell-of-origin. We did observe some overlap with H3.3K27M promoting negative enrichment of TNFA_Signaling_Via_NFKB in both models. Our study suggests that the tumorigenic effects of H3.3K27M are cell-of-origin dependent, with H3.3K27M being more oncogenic in Nestin+ cells than Olig2+ cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.