ArticleNature communications2021
Defective metabolic programming impairs early neuronal morphogenesis in neural cultures and an organoid model of Leigh syndrome.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06967831 (Using iPSC Derived Human Basal Ganglia Neurons From Patients With Leigh Syndrome for Metabolic Studies, Assay Development, and Drug Repurposing.), which is not on this map. Cited by 85 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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.
Using iPSC Derived Human Basal Ganglia Neurons From Patients With Leigh Syndrome for Metabolic Studies, Assay Development, and Drug Repurposing.
Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Modelling mitochondrial diseases in neuronsJournal of neuromuscular diseases · 2025Pooled it
- Glial Dysfunction and Memory Impairments in a Model of Pediatric Obstructive Sleep Apnea.Glia · 2026Article
- The role of impaired mitochondrial function in neurological manifestations of mitochondrial diseases.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Functional Mapping of Neurodevelopmental Disease Pathways to Key Neurodevelopmental Processes Represented in the Developmental Neurotoxicity In Vitro Testing Battery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitochondrial DNA heteroplasmy drives cortical neuronal disturbances in human organoids harbouring the common m.3243A>G mutation.Nature communications · 2026Article
- Prenatal THC exposure disrupts mitochondrial respiratory gene programs and medium spiny neuron maturation trajectories in the nucleus accumbens.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial complex I deficiency-associated diseases and models.Cellular and molecular life sciences : CMLS · 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
- MeCP2 dysregulation inhibits mitophagy and impairs neural development in cortical organoids.Journal of advanced research · 2026Article
- Pluripotent stem-cell-based screening uncovers sildenafil as a mitochondrial disease therapy.Cell · 2026Article
- Organoids for Metabolic Disease Modeling.Journal of inherited metabolic disease · 2026Review
- Reversibility and therapeutic feasibility of DNM1L-associated neurodevelopmental disorders.Experimental & molecular medicine · 2026Article
- Loss of function variants in HPDL impair human cortical development via alterations of mitochondrial function.Cell death & disease · 2026Article
- A metabolic safety valve for reductive stress.Nature metabolism · 2026Article
- Impaired Complex I dysregulates neural/glial precursors and corpus callosum development revealing postnatal defects in Leigh syndrome mice.EMBO molecular medicine · 2026Article
- PGC-1α: key regulator of mitochondrial biogenesis and cellular differentiation in metabolic and regenerative tissues.Cell & bioscience · 2025Review
- Advances and challenges in modeling Charcot-Marie-Tooth type 2A using iPSC-derived models.Stem cell reports · 2025Review
- Dysfunctional LHX6 pallido-subthalamic projections mediate epileptic events in a mouse model of Leigh syndrome.The Journal of clinical investigation · 2025Article
- Development of Cellular Energy Metabolism During Differentiation of Human iPSCs into Cortical Neurons.Molecular neurobiology · 2025Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
33 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leigh syndrome (LS) is a severe manifestation of mitochondrial disease in children and is currently incurable. The lack of effective models hampers our understanding of the mechanisms underlying the neuronal pathology of LS. Using patient-derived induced pluripotent stem cells and CRISPR/Cas9 engineering, we developed a human model of LS caused by mutations in the complex IV assembly gene SURF1. Single-cell RNA-sequencing and multi-omics analysis revealed compromised neuronal morphogenesis in mutant neural cultures and brain organoids. The defects emerged at the level of neural progenitor cells (NPCs), which retained a glycolytic proliferative state that failed to instruct neuronal morphogenesis. LS NPCs carrying mutations in the complex I gene NDUFS4 recapitulated morphogenesis defects. SURF1 gene augmentation and PGC1A induction via bezafibrate treatment supported the metabolic programming of LS NPCs, leading to restored neuronal morphogenesis. Our findings provide mechanistic insights and suggest potential interventional strategies for a rare mitochondrial disease.
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