ArticleTranslational psychiatry2018
Shared effects of DISC1 disruption and elevated WNT signaling in human cerebral organoids.
Article in Translational psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 68 citations in OpenAlex.
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- Hypoxia-ischemia and sexual dimorphism: modeling mitochondrial dysfunction using brain organoids.Cell & bioscience · 2025Review
- Modelling human brain development and disease with organoids.Nature reviews. Molecular cell biology · 2025Review
- 11.7T Diffusion Magnetic Resonance Imaging and Tractography to Probe Human Brain Organoid Microstructure.Biological psychiatry global open science · 2024Article
- Guidelines for Manufacturing and Application of Organoids: Brain.International journal of stem cells · 2024Article
- Mitochondrial metabolism in neural stem cells and implications for neurodevelopmental and neurodegenerative diseases.Journal of translational medicine · 2024Review
- Genetics of human brain development.Nature reviews. Genetics · 2024Review
- Bipolar disorder-iPSC derived neural progenitor cells exhibit dysregulation of store-operated CaMolecular psychiatry · 2023Article
- Involvement of an Aberrant Vascular System in Neurodevelopmental, Neuropsychiatric, and Neuro-Degenerative Diseases.Life (Basel, Switzerland) · 2023Review
- Functional bioengineered models of the central nervous system.Nature reviews bioengineering · 2023Review
- Current advancements of modelling schizophrenia using patient-derived induced pluripotent stem cells.Acta neuropathologica communications · 2022Review
- Human cerebral organoids - a new tool for clinical neurology research.Nature reviews. Neurology · 2022Review
- Advances in construction and modeling of functional neural circuits in vitro.Neurochemical research · 2022Article
- Human-Induced Pluripotent Stem Cell Technology: Toward the Future of Personalized Psychiatry.Journal of personalized medicine · 2022Review
- Review
- Schizophrenia is defined by cell-specific neuropathology and multiple neurodevelopmental mechanisms in patient-derived cerebral organoids.Molecular psychiatry · 2022Article
- Region Specific Brain Organoids to Study Neurodevelopmental Disorders.International journal of stem cells · 2022Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The development of three-dimensional culture methods has allowed for the study of developing cortical morphology in human cells. This provides a new tool to study the neurodevelopmental consequences of disease-associated mutations. Here, we study the effects of isogenic DISC1 mutation in cerebral organoids. DISC1 has been implicated in psychiatric disease based on genetic studies, including its interruption by a balanced translocation that increases the risk of major mental illness. Isogenic wild-type and DISC1-disrupted human-induced pluripotent stem cells were used to generate cerebral organoids, which were then examined for morphology and gene expression. We show that DISC1-mutant cerebral organoids display disorganized structural morphology and impaired proliferation, which is phenocopied by WNT agonism and rescued by WNT antagonism. Furthermore, there are many shared changes in gene expression with DISC1 disruption and WNT agonism, including in neural progenitor and cell fate markers, regulators of neuronal migration, and interneuron markers. These shared gene expression changes suggest mechanisms for the observed morphologic dysregulation with DISC1 disruption and points to new avenues for future studies. The shared changes in three-dimensional cerebral organoid morphology and gene expression with DISC1 interruption and WNT agonism further strengthens the link between DISC1 mutation, abnormalities in WNT signaling, and neuropsychiatric disease.
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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.