ArticleCell death & disease2014
Functional and molecular defects of hiPSC-derived neurons from patients with ATM deficiency.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Biomarkers in Ataxia-Telangiectasia: a Systematic Review.Journal of neurology · 2025Pooled it
- RNA Sequencing in Disease Diagnosis.Annual review of genomics and human genetics · 2024Review
- A-T neurodegeneration and DNA damage-induced transcriptional stress.DNA repair · 2024Review
- Defective repair of topoisomerase I induced chromosomal damage in Huntington's disease.Cellular and molecular life sciences : CMLS · 2022Article
- A guide for the diagnosis of rare and undiagnosed disease: beyond the exome.Genome medicine · 2022Review
- Reprogramming and differentiation-dependent transcriptional alteration of DNA damage response and apoptosis genes in human induced pluripotent stem cells.Journal of radiation research · 2019Article
- DNA damage and transcriptional regulation in iPSC-derived neurons from Ataxia Telangiectasia patients.Scientific reports · 2019Article
- Organs to Cells and Cells to Organoids: The Evolution ofFrontiers in cellular neuroscience · 2019Review
- Modeling rare diseases with induced pluripotent stem cell technology.Molecular and cellular probes · 2018Review
- Anti-AMPA GluA3 antibodies in Frontotemporal dementia: a new molecular target.Scientific reports · 2017Article
- The X-Linked Intellectual Disability Protein IL1RAPL1 Regulates Dendrite Complexity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Genome integrity and disease prevention in the nervous system.Genes & development · 2017Review
- Mitochondrial protein-linked DNA breaks perturb mitochondrial gene transcription and trigger free radical-induced DNA damage.Science advances · 2017Article
- Mobile phone signal exposure triggers a hormesis-like effect in AtmScientific reports · 2016Article
- Knockdown of NFBD1/MDC1 enhances chemosensitivity to cisplatin or 5-fluorouracil in nasopharyngeal carcinoma CNE1 cells.Molecular and cellular biochemistry · 2016Article
- Article
- Utility of Induced Pluripotent Stem Cells for the Study and Treatment of Genetic Diseases: Focus on Childhood Neurological Disorders.Frontiers in molecular neuroscience · 2016Review
- Infection of a Single Cell Line with Distinct Strains of Human Cytomegalovirus Can Result in Large Variations in Virion Production and Facilitate Efficient Screening of Virus Protein Function.Journal of virology · 2015Article
- A novel mouse model for ataxia-telangiectasia with a N-terminal mutation displays a behavioral defect and a low incidence of lymphoma but no increased oxidative burden.Human molecular genetics · 2015Article
- A novel porcine model of ataxia telangiectasia reproduces neurological features and motor deficits of human disease.Human molecular genetics · 2015Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Loss of ataxia telangiectasia mutated (ATM) kinase, a key factor of the DNA damage response (DDR) pathway, causes the cancer predisposing and neurodegenerative syndrome ataxia-telangiectasia (A-T). To investigate the mechanisms of neurodegeneration, we have reprogrammed fibroblasts from ATM-null A-T patients and normal controls to pluripotency (human-induced pluripotent stem cells), and derived from these neural precursor cells able to terminally differentiate into post-mitotic neurons positive to >90% for β-tubulin III+/microtubule-associated protein 2+. We show that A-T neurons display similar voltage-gated potassium and sodium currents and discharges of action potentials as control neurons, but defective expression of the maturation and synaptic markers SCG10, SYP and PSD95 (postsynaptic density protein 95). A-T neurons exhibited defective repair of DNA double-strand breaks (DSBs) and repressed phosphorylation of ATM substrates (e.g., γH2AX, Smc1-S966, Kap1-S824, Chk2-T68, p53-S15), but normal repair of single-strand breaks, and normal short- and long-patch base excision repair activities. Moreover, A-T neurons were resistant to apoptosis induced by the genotoxic agents camptothecin and trabectedin, but as sensitive as controls to the oxidative agents. Most notably, A-T neurons exhibited abnormal accumulation of topoisomerase 1-DNA covalent complexes (Top1-ccs). These findings reveal that ATM deficiency impairs neuronal maturation, suppresses the response and repair of DNA DSBs, and enhances Top1-cc accumulation. Top1-cc could be a risk factor for neurodegeneration as they may interfere with transcription elongation and promote transcriptional decline.
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Registered trials
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