ArticlePloS one2016
IDH1R132H in Neural Stem Cells: Differentiation Impaired by Increased Apoptosis.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- Joubert syndrome-derived induced pluripotent stem cells show altered neuronal differentiation in vitro.Cell and tissue research · 2024Article
- The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer.Acta pharmaceutica Sinica. B · 2023Review
- Integrative multi-omic analysis reveals neurodevelopmental gene dysregulation in CIC-knockout and IDH1-mutant cells.The Journal of pathology · 2022Article
- Giant Intracranial Xanthoma with Cloudy Vision as the First Symptom: A Case Report and Literature Review.International journal of general medicine · 2021Article
- Current biomarker-associated procedures of cancer modeling-a reference in the context of IDH1 mutant glioma.Cell death & disease · 2020Review
- To be Wild or Mutant: Role of Isocitrate Dehydrogenase 1 (IDH1) and 2-Hydroxy Glutarate (2-HG) in Gliomagenesis and Treatment Outcome in Glioma.Cellular and molecular neurobiology · 2020Review
- Gaps and Doubts in Search to Recognize Glioblastoma Cellular Origin and Tumor Initiating Cells.Journal of oncology · 2020Review
- Generation of induced neural stem cells with inducible IDH1R132H for analysis of glioma development and drug testing.PloS one · 2020Article
- Molecular Pathogenesis of Low-Grade Glioma.Neurosurgery clinics of North America · 2019Review
- Far Upstream Element-Binding Protein 1 Regulates LSD1 Alternative Splicing to Promote Terminal Differentiation of Neural Progenitors.Stem cell reports · 2018Article
- Beyond Brooding on Oncometabolic Havoc in IDH-Mutant Gliomas and AML: Current and Future Therapeutic Strategies.Cancers · 2018Review
- Molecular Mechanisms Governing the Stem Cell's Fate in Brain Cancer: Factors of Stemness and Quiescence.Frontiers in cellular neuroscience · 2018Review
- Isocitrate dehydrogenase 1 mutation subtypes at site 132 and their translational potential in glioma.CNS oncology · 2018Article
- Article
- Low-Grade Astrocytoma Mutations in IDH1, P53, and ATRX Cooperate to Block Differentiation of Human Neural Stem Cells via Repression of SOX2.Cell reports · 2017Article
- Mutant IDH1 Disrupts the Mouse Subventricular Zone and Alters Brain Tumor Progression.Molecular cancer research : MCR · 2017Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe high frequency of mutations in the isocitrate dehydrogenase 1 (IDH1) gene in diffuse gliomas indicates its importance in the process of gliomagenesis. These mutations result in loss of the normal function and acquisition of the neomorphic activity converting α-ketoglutarate to 2-hydroxyglutarate. This potential oncometabolite may induce the epigenetic changes, resulting in the deregulated expression of numerous genes, including those related to the differentiation process or cell survivability.
methodsNeural stem cells were derived from human induced pluripotent stem cells following embryoid body formation. Neural stem cells transduced with mutant IDH1R132H, empty vector, non-transduced and overexpressing IDH1WT controls were differentiated into astrocytes and neurons in culture. The neuronal and astrocytic differentiation was determined by morphology and expression of lineage specific markers (MAP2, Synapsin I and GFAP) as determined by real-time PCR and immunocytochemical staining. Apoptosis was evaluated by real-time observation of Caspase-3 activation and measurement of PARP cleavage by Western Blot.
resultsCompared with control groups, cells expressing IDH1R132H retained an undifferentiated state and lacked morphological changes following stimulated differentiation. The significant inhibitory effect of IDH1R132H on neuronal and astrocytic differentiation was confirmed by immunocytochemical staining for markers of neural stem cells. Additionally, real-time PCR indicated suppressed expression of lineage markers. High percentage of apoptotic cells was detected within IDH1R132H-positive neural stem cells population and their derivatives, if compared to normal neural stem cells and their derivatives. The analysis of PARP and Caspase-3 activity confirmed apoptosis sensitivity in mutant protein-expressing neural cells.
conclusionsOur study demonstrates that expression of IDH1R132H increases apoptosis susceptibility of neural stem cells and their derivatives. Robust apoptosis causes differentiation deficiency of IDH1R132H-expressing cells.
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