ArticleDevelopment (Cambridge, England)2022
Human iPSC-derived cerebral organoids model features of Leigh syndrome and reveal abnormal corticogenesis.
Article in Development (Cambridge, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
What it found
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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
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Modelling mitochondrial diseases in neuronsJournal of neuromuscular diseases · 2025Pooled it
- The role of impaired mitochondrial function in neurological manifestations of mitochondrial diseases.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Linking neurogenesis, oligodendrogenesis, and myelination defects to neurodevelopmental disruption in primary mitochondrial disorders.FEBS letters · 2026Review
- Accelerating Leigh syndrome drug discovery through deep learning screening in brain organoids.Nature communications · 2026Article
- Pluripotent stem-cell-based screening uncovers sildenafil as a mitochondrial disease therapy.Cell · 2026Article
- Loss of function variants in HPDL impair human cortical development via alterations of mitochondrial function.Cell death & disease · 2026Article
- Glucose and Oxygen Metabolism Coordinate Human Cortical Developmental Decisions.bioRxiv : the preprint server for biology · 2025Article
- Neuronal branching in stem cell models of mitochondrial and neurological diseases.Stem cells (Dayton, Ohio) · 2025Review
- Effects of heterozygous SMG1 mutations on nonsense-mediated mRNA decay in human pluripotent stem cell model.Molecules and cells · 2025Article
- Human TSC2 mutant cells exhibit aberrations in early neurodevelopment accompanied by changes in the DNA Methylome.Human molecular genetics · 2025Article
- Leptomeningeal Neural Organoid Fusions as Models to Study Meninges-Brain Signaling.Stem cells and development · 2025Article
- Preclinical models of mitochondrial dysfunction: mtDNA and nuclear-encoded regulators in diverse pathologies.Frontiers in aging · 2025Review
- Advancements in theFrontiers in toxicology · 2025Review
- Disease models of Leigh syndrome: From yeast to organoids.Journal of inherited metabolic disease · 2024Review
- Fetal and obstetrics manifestations of mitochondrial diseases.Journal of translational medicine · 2024Review
- Mutant huntingtin impairs neurodevelopment in human brain organoids through CHCHD2-mediated neurometabolic failure.Nature communications · 2024Article
- Functional overlap of inborn errors of immunity and metabolism genes defines T cell metabolic vulnerabilities.Science immunology · 2024Article
- Human In Vitro Models of Neuroenergetics and Neurometabolic Disturbances: Current Advances and Clinical Perspectives.Stem cells translational medicine · 2024Review
- Human TSC2 Mutant Cells Exhibit Aberrations in Early Neurodevelopment Accompanied by Changes in the DNA Methylome.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Leigh syndrome (LS) is a rare, inherited neurometabolic disorder that presents with bilateral brain lesions caused by defects in the mitochondrial respiratory chain and associated nuclear-encoded proteins. We generated human induced pluripotent stem cells (iPSCs) from three LS patient-derived fibroblast lines. Using whole-exome and mitochondrial sequencing, we identified unreported mutations in pyruvate dehydrogenase (GM0372, PDH; GM13411, MT-ATP6/PDH) and dihydrolipoyl dehydrogenase (GM01503, DLD). These LS patient-derived iPSC lines were viable and capable of differentiating into progenitor populations, but we identified several abnormalities in three-dimensional differentiation models of brain development. LS patient-derived cerebral organoids showed defects in neural epithelial bud generation, size and cortical architecture at 100 days. The double mutant MT-ATP6/PDH line produced organoid neural precursor cells with abnormal mitochondrial morphology, characterized by fragmentation and disorganization, and showed an increased generation of astrocytes. These studies aim to provide a comprehensive phenotypic characterization of available patient-derived cell lines that can be used to study Leigh syndrome.
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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.