ArticleCell stem cell2019
Direct Reprogramming of Human Neurons Identifies MARCKSL1 as a Pathogenic Mediator of Valproic Acid-Induced Teratogenicity.
Article in Cell stem cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Valproate Exposure as anCNS & neurological disorders drug targets · 2025Pooled it
- Self-organized anteroposterior regionalization of early midbrain and hindbrain/spinal cords using micropatterned human pluripotent stem cells.SLAS technology · 2026Article
- Unraveling the Morphological and Functional Maturation Mechanisms Underlying Human Neural Development Using iPSCs-Derived Neuronal Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dlgap2 deficiency disrupts synaptic homeostasis by promoting ubiquitin-mediated Itsn1 degradation in a valproic acid-induced autism-like model.Scientific reports · 2026Article
- Presynaptic Trafficking of Glutamate Decarboxylase Isoforms Is Dispensable for Basal GABAergic Neurotransmission.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- In vitro models of valproic acid to assess neurodevelopmental toxicity: A scoping review.Epilepsia · 2025Article
- Brain-Wide Neuroregenerative Gene Therapy Improves Cognition in a Mouse Model of Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Oolong tea attenuates neuroinflammation by modulating the microbiota-gut-brain axis in a rat model of autism.Frontiers in nutrition · 2025Article
- Prenatal exposure to valproic acid reduces synaptic δ-catenin levels and disrupts ultrasonic vocalization in neonates.Neuropharmacology · 2024Article
- Gephyrin promotes autonomous assembly and synaptic localization of GABAergic postsynaptic components without presynaptic GABA release.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Generation of human excitatory forebrain neurons by cooperative binding of proneural NGN2 and homeobox factor EMX1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Canalizing cell fate by transcriptional repression.Molecular systems biology · 2024Review
- Characterization of a Human Neuronal Culture System for the Study of Cofilin-Actin Rod Pathology.Biomedicines · 2023Article
- Efficient generation of functional neurons from mouse embryonic stem cells via neurogenin-2 expression.Nature protocols · 2023Review
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- MYT1L haploinsufficiency in human neurons and mice causes autism-associated phenotypes that can be reversed by genetic and pharmacologic intervention.Molecular psychiatry · 2023Article
- Article
- A Shared Pathogenic Mechanism for Valproic Acid and SHROOM3 Knockout in a Brain Organoid Model of Neural Tube Defects.bioRxiv : the preprint server for biology · 2023Article
- Bile Acids Induce Neurite Outgrowth in Nsc-34 Cells via TGR5 and a Distinct Transcriptional Profile.Pharmaceuticals (Basel, Switzerland) · 2023Article
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8 authors at 2 institutions in 1 country.
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Abstract
Human pluripotent stem cells can be rapidly converted into functional neurons by ectopic expression of proneural transcription factors. Here we show that directly reprogrammed neurons, despite their rapid maturation kinetics, can model teratogenic mechanisms that specifically affect early neurodevelopment. We delineated distinct phases of in vitro maturation during reprogramming of human neurons and assessed the cellular phenotypes of valproic acid (VPA), a teratogenic drug. VPA exposure caused chronic impairment of dendritic morphology and functional properties of developing neurons, but not those of mature neurons. These pathogenic effects were associated with VPA-mediated inhibition of the histone deacetylase (HDAC) and glycogen synthase kinase-3 (GSK-3) pathways, which caused transcriptional downregulation of many genes, including MARCKSL1, an actin-stabilizing protein essential for dendritic morphogenesis and synapse maturation during early neurodevelopment. Our findings identify a developmentally restricted pathogenic mechanism of VPA and establish the use of reprogrammed neurons as an effective platform for modeling teratogenic pathways.
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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.