ArticleFrontiers in molecular neuroscience2022
Valproic acid exposure decreases neurogenic potential of outer radial glia in human brain organoids.
Article in Frontiers in molecular neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Sex-dependent effects of imperatorin on autistic-like behaviors and BDNF signaling in rats prenatally exposed to valproic acid.IBRO neuroscience reports · 2026Article
- The molecular footprint of valproic acid in human hippocampal organoid.Molecular neurobiology · 2026Article
- Multiomics analysis identifies VPA-induced changes in neural progenitor cells, ventricular-like regions, and cellular microenvironment in dorsal forebrain organoids.Molecular psychiatry · 2026Article
- Organoid intelligence: a promising paradigm for autism spectrum disorder research.Molecular psychiatry · 2026Review
- Differential Neurodevelopmental Disruption by Bisphenol A (BPA) and Valproic Acid (VPA) in Human Forebrain Organoids.bioRxiv : the preprint server for biology · 2026Article
- Organoids in drug development: from predictive models to regulatory integration.Drug discovery today · 2026Review
- Progenitor diversity during formation of the mammalian neocortex.Frontiers in neuroscience · 2026Review
- Stem Cell Therapy and Models for Autism Spectrum Disorder: Insights and Research.Current neuropharmacology · 2026Review
- Article
- Valproate-Induced Autism and Sexual Hormone Disturbances: A Literature Review and Hypotheses.Neurochemical research · 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
- Human organoids potentially boost research into environmental factors of neural tube defects.Reproductive toxicology (Elmsford, N.Y.) · 2025Review
- Chronic haloperidol exposure impairs neurodevelopment via Notch1 signaling in human stem cell-derived brain organoids.Scientific reports · 2025Article
- In vitro models of valproic acid to assess neurodevelopmental toxicity: A scoping review.Epilepsia · 2025Article
- Human Brain Organoids Model Abnormal Prenatal Neural Development Induced by Thermal Stimulation.Cell proliferation · 2025Article
- Establishment of nasal and olfactory epithelium organoids for unveiling mechanism of tissue regeneration and pathogenesis of nasal diseases.Cellular and molecular life sciences : CMLS · 2025Review
- Small molecule valproic acid enhances ventral patterning of human neural tube organoids by regulating Wnt and Shh signalling.Cell proliferation · 2025Article
- Unraveling the complexity of cognitive impairment following high-altitude exposure: from preclinical animal models to human organoids.Frontiers in neuroscience · 2025Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Valproic acid (VPA) exposure during pregnancy leads to a higher risk of autism spectrum disorder (ASD) susceptibility in offspring. Human dorsal forebrain organoids were used to recapitulate course of cortical neurogenesis in the developing human brain. Combining morphological characterization with massive parallel RNA sequencing (RNA-seq) on organoids to analyze the pathogenic effects caused by VPA exposure and critical signaling pathway. We found that VPA exposure in organoids caused a reduction in the size and impairment in the proliferation and expansion of neural progenitor cells (NPCs) in a dose-dependent manner. VPA exposure typically decreased the production of outer radial glia-like cells (oRGs), a subtype of NPCs contributing to mammalian neocortical expansion and delayed their fate toward upper-layer neurons. Transcriptomics analysis revealed that VPA exposure influenced ASD risk gene expression in organoids, which markedly overlapped with irregulated genes in brains or organoids originating from ASD patients. We also identified that VPA-mediated Wnt/β-catenin signaling pathway activation is essential for sustaining cortical neurogenesis and oRGs output. Taken together, our study establishes the use of dorsal forebrain organoids as an effective platform for modeling VPA-induced teratogenic pathways involved in the cortical neurogenesis and oRGs output, which might contribute to ASD pathogenesis in the developing brain.
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Registered trials
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