ArticleCell reports2022
2-Hydroxyglutarate destabilizes chromatin regulatory landscape and lineage fidelity to promote cellular heterogeneity.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 23 citations in OpenAlex.
- l-2-Hydroxyglutarate impairs neuronal differentiation through epigenetic activation of MYC expression.The Journal of clinical investigation · 2026Article
- Mitochondrial uncoupling inhibits serine catabolismCancer biology & medicine · 2026Article
- 2-Hydroxyglutarate in onco-pathway: a metabolic driver of proto-oncogene activation.Frontiers in oncology · 2026Review
- Multidimensional roles and clinical significance of GATA3 in breast cancer.Frontiers in cell and developmental biology · 2026Review
- Inhibition of scheggia/SLC25A1 citrate transporter alleviates XPD deficits.Scientific reports · 2025Article
- Epigenetic-mediated positive feedback loop facilitates the progression of lung adenocarcinoma.iScience · 2025Article
- Cancer progression through the lens of age-induced metabolic reprogramming.Nature reviews. Cancer · 2025Review
- 2-hydroxyglutarate mediates whitening of brown adipocytes coupled to nuclear softening upon mitochondrial dysfunction.Nature metabolism · 2025Article
- Application of mass cytometry in the immune microenvironment of breast cancer.Medical oncology (Northwood, London, England) · 2025Review
- A metabolic shift to the serine pathway induced by lipids fosters epigenetic reprogramming in nontransformed breast cells.Science advances · 2025Article
- A genetically encoded fluorescent sensor enables sensitive and specific detection of IDH mutant associated oncometabolite D-2-hydroxyglutarate.BMC cancer · 2025Article
- Review
- Distinct dynamics of parental 5-hydroxymethylcytosine during human preimplantation development regulate early lineage gene expression.Nature cell biology · 2024Article
- The curious case of IDH mutant acute myeloid leukaemia: biochemistry and therapeutic approaches.Biochemical Society transactions · 2023Review
- The Transcriptional and Epigenetic Landscape of Cancer Cell Lineage Plasticity.Cancer discovery · 2023Review
- Roles of Chromatin Remodelling and Molecular Heterogeneity in Therapy Resistance in Glioblastoma.Cancers · 2022Review
- Chromatin Variants Reveal the Genetic Determinants of Oncogenesis in Breast Cancer.Cold Spring Harbor perspectives in medicine · 2022Review
- Mapping Phenotypic Plasticity upon the Cancer Cell State Landscape Using Manifold Learning.Cancer discovery · 2022Article
- Apex Predator Nematodes and Meso-Predator Bacteria Consume Their Basal Insect Prey through Discrete Stages of Chemical Transformations.mSystems · 2022Article
- Monitoring response to a clinically relevant IDH inhibitor in glioma-HyperpolarizedNeuro-oncology advancesArticle
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The epigenome delineates lineage-specific transcriptional programs and restricts cell plasticity to prevent non-physiological cell fate transitions. Although cell diversification fosters tumor evolution and therapy resistance, upstream mechanisms that regulate the stability and plasticity of the cancer epigenome remain elusive. Here we show that 2-hydroxyglutarate (2HG) not only suppresses DNA repair but also mediates the high-plasticity chromatin landscape. A combination of single-cell epigenomics and multi-omics approaches demonstrates that 2HG disarranges otherwise well-preserved stable nucleosome positioning and promotes cell-to-cell variability. 2HG induces loss of motif accessibility to the luminal-defining transcriptional factors FOXA1, FOXP1, and GATA3 and a shift from luminal to basal-like gene expression. Breast tumors with high 2HG exhibit enhanced heterogeneity with undifferentiated epigenomic signatures linked to adverse prognosis. Further, ascorbate-2-phosphate (A2P) eradicates heterogeneity and impairs growth of high 2HG-producing breast cancer cells. These findings suggest 2HG as a key determinant of cancer plasticity and provide a rational strategy to counteract tumor cell evolution.
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Registered trials
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.