ArticleTranslational psychiatry2022
Human forebrain organoids reveal connections between valproic acid exposure and autism risk.
Article in Translational psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 2 of them syntheses that pooled it.
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Who cites it
44 citing papers in PubMed, 2 syntheses or guidelines pooled it, 63 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Valproate Exposure as anCNS & neurological disorders drug targets · 2025Pooled it
- Multiomics analysis identifies VPA-induced changes in neural progenitor cells, ventricular-like regions, and cellular microenvironment in dorsal forebrain organoids.Molecular psychiatry · 2026Article
- Assessing molecular gene by treatment interactions using a population of neural progenitors exposed to valproic acid and lithium.Molecular psychiatry · 2026Article
- Prenatal valproic acid exposure alters striatal proteomic signatures associated with autism spectrum disorder in mice.Translational psychiatry · 2026Article
- The anti-NMDAR1 antibodies and IL-17 signaling pathway shape NMDAR encephalitis.Molecular psychiatry · 2026Article
- Differential Neurodevelopmental Disruption by Bisphenol A (BPA) and Valproic Acid (VPA) in Human Forebrain Organoids.bioRxiv : the preprint server for biology · 2026Article
- Image-based epigenetic profiling with deep learning and high-speed super-resolution microscopy.Epigenetics & chromatin · 2026Article
- Dlgap2 deficiency disrupts synaptic homeostasis by promoting ubiquitin-mediated Itsn1 degradation in a valproic acid-induced autism-like model.Scientific reports · 2026Article
- Disturbances of paraventricular thalamic nucleus neurons in bipolar disorder revealed by single-nucleus analysis.Nature communications · 2026Article
- Stem Cell Therapy and Models for Autism Spectrum Disorder: Insights and Research.Current neuropharmacology · 2026Review
- Article
- Alternative methods for developmental toxicity testing: features, status and future directions.Journal of veterinary science · 2025Review
- Sulforaphane protects developing neural networks from VPA-induced synaptic alterations.Molecular psychiatry · 2025Article
- Towards a quality control framework for cerebral cortical organoids.Scientific reports · 2025Article
- The ADCY1-mediated cAMP signaling pathway mediates functional effects of montelukast treatment in brain organoids.Cellular and molecular life sciences : CMLS · 2025Article
- Review
- Cerebral organoid research for pediatric patients with neurological disorders.Clinical and experimental pediatrics · 2025Article
- Neural Excitatory/Inhibitory Imbalance in Motor Aging: From Genetic Mechanisms to Therapeutic Challenges.Biology · 2025Review
- Human Brain Organoids Model Abnormal Prenatal Neural Development Induced by Thermal Stimulation.Cell proliferation · 2025Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Valproic acid (VPA) exposure as an environmental factor that confers risk of autism spectrum disorder (ASD), its functional mechanisms in the human brain remain unclear since relevant studies are currently restricted to two-dimensional cell cultures and animal models. To identify mechanisms by which VPA contribute to ASD risk in human, here we used human forebrain organoids (hFOs), in vitro derived three-dimensional cell cultures that recapitulate key human brain developmental features. We identified that VPA exposure in hFOs affected the expression of genes enriched in neural development, synaptic transmission, oxytocin signaling, calcium, and potassium signaling pathways, which have been implicated in ASD. Genes (e.g., CAMK4, CLCN4, DPP10, GABRB3, KCNB1, PRKCB, SCN1A, and SLC24A2) that affected by VPA were significantly overlapped with those dysregulated in brains or organoids derived from ASD patients, and known ASD risk genes, as well as genes in ASD risk-associated gene coexpression modules. Single-cell RNA sequencing analysis showed that VPA exposure affected the expression of genes in choroid plexus, excitatory neuron, immature neuron, and medial ganglionic eminence cells annotated in hFOs. Microelectrode array further identified that VPA exposure in hFOs disrupted synaptic transmission. Taken together, this study connects VPA exposure to ASD pathogenesis using hFOs, which is valuable for illuminating the etiology of ASD and screening for potential therapeutic targets.
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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.