ArticleThe American journal of psychiatry2024
Recapitulation of Perturbed Striatal Gene Expression Dynamics of Donors' Brains With Ventral Forebrain Organoids Derived From the Same Individuals With Schizophrenia.
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Article in The American journal of psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 2 of them syntheses that pooled it.
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9citing papers in PubMed, 2 pooled it
2.5field-weighted citation impact, top 11% of its field
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Who cites it
9 citing papers in PubMed, 2 syntheses or guidelines pooled it, 16 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Dissecting Schizophrenia Biology Using Pleiotropy With Cognitive Genomics.Biological psychiatry · 2025Pooled it
- Gestational Hypoxia Disrupts Medial Ganglionic Eminence Progenitor Dynamics and Interneuron Development in Schizophrenia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Analysis of gene co-expression connectivity dynamics implicates aberrant neuron-oligodendroglia interactions in schizophrenia.Nature communications · 2026Article
- Advances and applications of brain organoids in central nervous system disorders: Bridging the gap from laboratory to clinic.Neural regeneration research · 2026Article
- SETD1A regulates psychiatric gene networks involved in genomic stability and synaptic function in rare and sporadic schizophrenia.Nature communications · 2025Article
- Lower density of calretinin-immunopositive neurons in the putamen of subjects with schizophrenia.Journal of anatomy · 2025Article
- Harnessing stem cell-based approaches for clinically meaningful discoveries in schizophrenia.Schizophrenia research · 2024Article
- Cell type specification and diversity in subpallial organoids.Frontiers in genetics · 2024Review
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Tomoyo SawadaLieber Institute for Brain Development, Baltimore (Sawada, Barbosa, Araujo, McCord, D'Ignazio, Benjamin, Sheehan, Feltrin, Arora, Brandtjen, Kleinman, Hyde, Weinberger, Paquola, Erwin); Department of Neurology (D'Ignazio, Benjamin, Kleinman, Hyde, Weinberger, Paquola, Erwin), Department of Psychiatry and Behavioral Sciences (Benjamin, Kleinman, Hyde, Weinberger), and Department of Neuroscience (Weinberger, Erwin), Johns Hopkins School of Medicine, Baltimore; South Australian Health and Medical Research Institute, Laboratory for Human Neurophysiology and Genetics, Adelaide (Zabolocki, Bardy); Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide (Zabolocki, Bardy).
André R BarbosaLieber Institute for Brain Development, Baltimore (Sawada, Barbosa, Araujo, McCord, D'Ignazio, Benjamin, Sheehan, Feltrin, Arora, Brandtjen, Kleinman, Hyde, Weinberger, Paquola, Erwin); Department of Neurology (D'Ignazio, Benjamin, Kleinman, Hyde, Weinberger, Paquola, Erwin), Department of Psychiatry and Behavioral Sciences (Benjamin, Kleinman, Hyde, Weinberger), and Department of Neuroscience (Weinberger, Erwin), Johns Hopkins School of Medicine, Baltimore; South Australian Health and Medical Research Institute, Laboratory for Human Neurophysiology and Genetics, Adelaide (Zabolocki, Bardy); Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide (Zabolocki, Bardy).
Bruno AraujoLieber Institute for Brain Development, Baltimore (Sawada, Barbosa, Araujo, McCord, D'Ignazio, Benjamin, Sheehan, Feltrin, Arora, Brandtjen, Kleinman, Hyde, Weinberger, Paquola, Erwin); Department of Neurology (D'Ignazio, Benjamin, Kleinman, Hyde, Weinberger, Paquola, Erwin), Department of Psychiatry and Behavioral Sciences (Benjamin, Kleinman, Hyde, Weinberger), and Department of Neuroscience (Weinberger, Erwin), Johns Hopkins School of Medicine, Baltimore; South Australian Health and Medical Research Institute, Laboratory for Human Neurophysiology and Genetics, Adelaide (Zabolocki, Bardy); Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide (Zabolocki, Bardy).
Alejandra E McCordLieber Institute for Brain Development, Baltimore (Sawada, Barbosa, Araujo, McCord, D'Ignazio, Benjamin, Sheehan, Feltrin, Arora, Brandtjen, Kleinman, Hyde, Weinberger, Paquola, Erwin); Department of Neurology (D'Ignazio, Benjamin, Kleinman, Hyde, Weinberger, Paquola, Erwin), Department of Psychiatry and Behavioral Sciences (Benjamin, Kleinman, Hyde, Weinberger), and Department of Neuroscience (Weinberger, Erwin), Johns Hopkins School of Medicine, Baltimore; South Australian Health and Medical Research Institute, Laboratory for Human Neurophysiology and Genetics, Adelaide (Zabolocki, Bardy); Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide (Zabolocki, Bardy).
Laura D'IgnazioLieber Institute for Brain Development, Baltimore (Sawada, Barbosa, Araujo, McCord, D'Ignazio, Benjamin, Sheehan, Feltrin, Arora, Brandtjen, Kleinman, Hyde, Weinberger, Paquola, Erwin); Department of Neurology (D'Ignazio, Benjamin, Kleinman, Hyde, Weinberger, Paquola, Erwin), Department of Psychiatry and Behavioral Sciences (Benjamin, Kleinman, Hyde, Weinberger), and Department of Neuroscience (Weinberger, Erwin), Johns Hopkins School of Medicine, Baltimore; South Australian Health and Medical Research Institute, Laboratory for Human Neurophysiology and Genetics, Adelaide (Zabolocki, Bardy); Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide (Zabolocki, Bardy).
Kynon J M BenjaminLieber Institute for Brain Development, Baltimore (Sawada, Barbosa, Araujo, McCord, D'Ignazio, Benjamin, Sheehan, Feltrin, Arora, Brandtjen, Kleinman, Hyde, Weinberger, Paquola, Erwin); Department of Neurology (D'Ignazio, Benjamin, Kleinman, Hyde, Weinberger, Paquola, Erwin), Department of Psychiatry and Behavioral Sciences (Benjamin, Kleinman, Hyde, Weinberger), and Department of Neuroscience (Weinberger, Erwin), Johns Hopkins School of Medicine, Baltimore; South Australian Health and Medical Research Institute, Laboratory for Human Neurophysiology and Genetics, Adelaide (Zabolocki, Bardy); Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide (Zabolocki, Bardy).
Bonna SheehanLieber Institute for Brain Development, Baltimore (Sawada, Barbosa, Araujo, McCord, D'Ignazio, Benjamin, Sheehan, Feltrin, Arora, Brandtjen, Kleinman, Hyde, Weinberger, Paquola, Erwin); Department of Neurology (D'Ignazio, Benjamin, Kleinman, Hyde, Weinberger, Paquola, Erwin), Department of Psychiatry and Behavioral Sciences (Benjamin, Kleinman, Hyde, Weinberger), and Department of Neuroscience (Weinberger, Erwin), Johns Hopkins School of Medicine, Baltimore; South Australian Health and Medical Research Institute, Laboratory for Human Neurophysiology and Genetics, Adelaide (Zabolocki, Bardy); Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide (Zabolocki, Bardy).
Michael ZabolockiLieber Institute for Brain Development, Baltimore (Sawada, Barbosa, Araujo, McCord, D'Ignazio, Benjamin, Sheehan, Feltrin, Arora, Brandtjen, Kleinman, Hyde, Weinberger, Paquola, Erwin); Department of Neurology (D'Ignazio, Benjamin, Kleinman, Hyde, Weinberger, Paquola, Erwin), Department of Psychiatry and Behavioral Sciences (Benjamin, Kleinman, Hyde, Weinberger), and Department of Neuroscience (Weinberger, Erwin), Johns Hopkins School of Medicine, Baltimore; South Australian Health and Medical Research Institute, Laboratory for Human Neurophysiology and Genetics, Adelaide (Zabolocki, Bardy); Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide (Zabolocki, Bardy).
Arthur FeltrinLieber Institute for Brain Development, Baltimore (Sawada, Barbosa, Araujo, McCord, D'Ignazio, Benjamin, Sheehan, Feltrin, Arora, Brandtjen, Kleinman, Hyde, Weinberger, Paquola, Erwin); Department of Neurology (D'Ignazio, Benjamin, Kleinman, Hyde, Weinberger, Paquola, Erwin), Department of Psychiatry and Behavioral Sciences (Benjamin, Kleinman, Hyde, Weinberger), and Department of Neuroscience (Weinberger, Erwin), Johns Hopkins School of Medicine, Baltimore; South Australian Health and Medical Research Institute, Laboratory for Human Neurophysiology and Genetics, Adelaide (Zabolocki, Bardy); Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide (Zabolocki, Bardy).
Ria AroraLieber Institute for Brain Development, Baltimore (Sawada, Barbosa, Araujo, McCord, D'Ignazio, Benjamin, Sheehan, Feltrin, Arora, Brandtjen, Kleinman, Hyde, Weinberger, Paquola, Erwin); Department of Neurology (D'Ignazio, Benjamin, Kleinman, Hyde, Weinberger, Paquola, Erwin), Department of Psychiatry and Behavioral Sciences (Benjamin, Kleinman, Hyde, Weinberger), and Department of Neuroscience (Weinberger, Erwin), Johns Hopkins School of Medicine, Baltimore; South Australian Health and Medical Research Institute, Laboratory for Human Neurophysiology and Genetics, Adelaide (Zabolocki, Bardy); Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide (Zabolocki, Bardy).
Anna C BrandtjenLieber Institute for Brain Development, Baltimore (Sawada, Barbosa, Araujo, McCord, D'Ignazio, Benjamin, Sheehan, Feltrin, Arora, Brandtjen, Kleinman, Hyde, Weinberger, Paquola, Erwin); Department of Neurology (D'Ignazio, Benjamin, Kleinman, Hyde, Weinberger, Paquola, Erwin), Department of Psychiatry and Behavioral Sciences (Benjamin, Kleinman, Hyde, Weinberger), and Department of Neuroscience (Weinberger, Erwin), Johns Hopkins School of Medicine, Baltimore; South Australian Health and Medical Research Institute, Laboratory for Human Neurophysiology and Genetics, Adelaide (Zabolocki, Bardy); Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide (Zabolocki, Bardy).
Joel E KleinmanLieber Institute for Brain Development, Baltimore (Sawada, Barbosa, Araujo, McCord, D'Ignazio, Benjamin, Sheehan, Feltrin, Arora, Brandtjen, Kleinman, Hyde, Weinberger, Paquola, Erwin); Department of Neurology (D'Ignazio, Benjamin, Kleinman, Hyde, Weinberger, Paquola, Erwin), Department of Psychiatry and Behavioral Sciences (Benjamin, Kleinman, Hyde, Weinberger), and Department of Neuroscience (Weinberger, Erwin), Johns Hopkins School of Medicine, Baltimore; South Australian Health and Medical Research Institute, Laboratory for Human Neurophysiology and Genetics, Adelaide (Zabolocki, Bardy); Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide (Zabolocki, Bardy).
Thomas M HydeLieber Institute for Brain Development, Baltimore (Sawada, Barbosa, Araujo, McCord, D'Ignazio, Benjamin, Sheehan, Feltrin, Arora, Brandtjen, Kleinman, Hyde, Weinberger, Paquola, Erwin); Department of Neurology (D'Ignazio, Benjamin, Kleinman, Hyde, Weinberger, Paquola, Erwin), Department of Psychiatry and Behavioral Sciences (Benjamin, Kleinman, Hyde, Weinberger), and Department of Neuroscience (Weinberger, Erwin), Johns Hopkins School of Medicine, Baltimore; South Australian Health and Medical Research Institute, Laboratory for Human Neurophysiology and Genetics, Adelaide (Zabolocki, Bardy); Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide (Zabolocki, Bardy).
Cedric BardyLieber Institute for Brain Development, Baltimore (Sawada, Barbosa, Araujo, McCord, D'Ignazio, Benjamin, Sheehan, Feltrin, Arora, Brandtjen, Kleinman, Hyde, Weinberger, Paquola, Erwin); Department of Neurology (D'Ignazio, Benjamin, Kleinman, Hyde, Weinberger, Paquola, Erwin), Department of Psychiatry and Behavioral Sciences (Benjamin, Kleinman, Hyde, Weinberger), and Department of Neuroscience (Weinberger, Erwin), Johns Hopkins School of Medicine, Baltimore; South Australian Health and Medical Research Institute, Laboratory for Human Neurophysiology and Genetics, Adelaide (Zabolocki, Bardy); Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide (Zabolocki, Bardy).
Daniel R WeinbergerLieber Institute for Brain Development, Baltimore (Sawada, Barbosa, Araujo, McCord, D'Ignazio, Benjamin, Sheehan, Feltrin, Arora, Brandtjen, Kleinman, Hyde, Weinberger, Paquola, Erwin); Department of Neurology (D'Ignazio, Benjamin, Kleinman, Hyde, Weinberger, Paquola, Erwin), Department of Psychiatry and Behavioral Sciences (Benjamin, Kleinman, Hyde, Weinberger), and Department of Neuroscience (Weinberger, Erwin), Johns Hopkins School of Medicine, Baltimore; South Australian Health and Medical Research Institute, Laboratory for Human Neurophysiology and Genetics, Adelaide (Zabolocki, Bardy); Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide (Zabolocki, Bardy).
Apuã C M PaquolaLieber Institute for Brain Development, Baltimore (Sawada, Barbosa, Araujo, McCord, D'Ignazio, Benjamin, Sheehan, Feltrin, Arora, Brandtjen, Kleinman, Hyde, Weinberger, Paquola, Erwin); Department of Neurology (D'Ignazio, Benjamin, Kleinman, Hyde, Weinberger, Paquola, Erwin), Department of Psychiatry and Behavioral Sciences (Benjamin, Kleinman, Hyde, Weinberger), and Department of Neuroscience (Weinberger, Erwin), Johns Hopkins School of Medicine, Baltimore; South Australian Health and Medical Research Institute, Laboratory for Human Neurophysiology and Genetics, Adelaide (Zabolocki, Bardy); Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide (Zabolocki, Bardy).
Jennifer A ErwinLieber Institute for Brain Development, Baltimore (Sawada, Barbosa, Araujo, McCord, D'Ignazio, Benjamin, Sheehan, Feltrin, Arora, Brandtjen, Kleinman, Hyde, Weinberger, Paquola, Erwin); Department of Neurology (D'Ignazio, Benjamin, Kleinman, Hyde, Weinberger, Paquola, Erwin), Department of Psychiatry and Behavioral Sciences (Benjamin, Kleinman, Hyde, Weinberger), and Department of Neuroscience (Weinberger, Erwin), Johns Hopkins School of Medicine, Baltimore; South Australian Health and Medical Research Institute, Laboratory for Human Neurophysiology and Genetics, Adelaide (Zabolocki, Bardy); Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide (Zabolocki, Bardy).
Johns Hopkins University · US
Funding
INTERDISCIPLINARY TRAINING PROGRAM IN NEUROSCIENCEST32MH015330 · NIMH · JOHNS HOPKINS UNIVERSITY · PI MARGOLIS, RUSSELL L · 1985 to 2024
$6.2MNIMH NIH HHS T32 MH015330
Abstract
objectiveSchizophrenia is a brain disorder that originates during neurodevelopment and has complex genetic and environmental etiologies. Despite decades of clinical evidence of altered striatal function in affected patients, studies examining its cellular and molecular mechanisms in humans are limited. To explore neurodevelopmental alterations in the striatum associated with schizophrenia, the authors established a method for the differentiation of induced pluripotent stem cells (iPSCs) into ventral forebrain organoids (VFOs).
methodsVFOs were generated from postmortem dural fibroblast-derived iPSCs of four individuals with schizophrenia and four neurotypical control individuals for whom postmortem caudate genotypes and transcriptomic data were profiled in the BrainSeq neurogenomics consortium. Individuals were selected such that the two groups had nonoverlapping schizophrenia polygenic risk scores (PRSs).
resultsSingle-cell RNA sequencing analyses of VFOs revealed differences in developmental trajectory between schizophrenia and control individuals in which inhibitory neuronal cells from the patients exhibited accelerated maturation. Furthermore, upregulated genes in inhibitory neurons in schizophrenia VFOs showed a significant overlap with upregulated genes in postmortem caudate tissue of individuals with schizophrenia compared with control individuals, including the donors of the iPSC cohort.
conclusionsThe findings suggest that striatal neurons derived from high-PRS individuals with schizophrenia carry abnormalities that originated during early brain development and that the VFO model can recapitulate disease-relevant cell type-specific neurodevelopmental phenotypes in a dish.
Indexed as
Basal ForebrainInduced Pluripotent Stem CellsOrganoidsSchizophreniaAdultCell DifferentiationCorpus StriatumFemaleHumansMaleNeuronsSingle-Cell AnalysisTranscriptomeGenetics/GenomicsSchizophrenia Spectrum and Other Psychotic Disorders
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