ArticleChemosphere2022
Neuronal differentiation pathways and compound-induced developmental neurotoxicity in the human neural progenitor cell test (hNPT) revealed by RNA-seq.
Article in Chemosphere, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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12 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Evaluation of developmental toxicity of chlorpyrifos through new approach methodologies: a systematic review.Archives of toxicology · 2025Pooled it
- Micropatterned neural induction with heat-inactivated extracellular matrix protein by on-demand high-speed laser.Regenerative therapy · 2026Article
- In vitro models of valproic acid to assess neurodevelopmental toxicity: A scoping review.Epilepsia · 2025Article
- Transcriptomic characterization of maturing neurons from human neural stem cells across developmental time points.IBRO neuroscience reports · 2025Article
- Current Applications of Human Pluripotent Stem Cells in Neuroscience Research and Cell Transplantation Therapy for Neurological Disorders.Stem cell reviews and reports · 2025Review
- Comprehensive RNA-seq analysis of benign prostatic hyperplasia (BPH) in rats exposed to testosterone and estradiol.Scientific reports · 2025Article
- Assessing the Neurodevelopmental Impact of Fluoxetine, Citalopram, and Paroxetine on Neural Stem Cell-Derived Neurons.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Recent advances and current challenges of new approach methodologies in developmental and adult neurotoxicity testing.Archives of toxicology · 2024Review
- Mechanisms of Neurotoxicity of Organophosphate Pesticides and Their Relation to Neurological Disorders.Neuropsychiatric disease and treatment · 2024Review
- Article
- The Threat Posed by Environmental Contaminants on Neurodevelopment: What Can We Learn from Neural Stem Cells?International journal of molecular sciences · 2023Review
- Prolonged Differentiation of Neuron-Astrocyte Co-Cultures Results in Emergence of Dopaminergic Neurons.International journal of molecular sciences · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
There is an increased awareness that the use of animals for compound-induced developmental neurotoxicity (DNT) testing has limitations. Animal-free innovations, especially the ones based on human stem cell-based models are pivotal in studying DNT since they can mimic processes relevant to human brain development. Here we present the human neural progenitor test (hNPT), a 10-day protocol in which neural progenitor cells differentiate into a neuron-astrocyte co-culture. The study aimed to characterise differentiation over time and to find neurodevelopmental processes sensitive to compound exposure using transcriptomics. 3992 genes regulated in unexposed control cultures (p ≤ 0.001, log2FC ≥ 1) showed Gene Ontology (GO-) term enrichment for neuronal and glial differentiation, neurite extension, synaptogenesis, and synaptic transmission. Exposure to known or suspected DNT compounds (acrylamide, chlorpyrifos, fluoxetine, methyl mercury, or valproic acid) at concentrations resulting in 95% cell viability each regulated unique combinations of GO-terms relating to neural progenitor proliferation, neuronal and glial differentiation, axon development, synaptogenesis, synaptic transmission, and apoptosis. Investigation of the GO-terms 'neuron apoptotic process' and 'axon development' revealed common genes that were responsive across compounds, and might be used as biomarkers for DNT. The GO-term 'synaptic signalling', on the contrary, whilst also responsive to all compounds tested, showed little overlap in gene expression regulation patterns between the conditions. This GO-term may articulate compound-specific effects that may be relevant for revealing differences in mechanism of toxicity. Given its focus on neural progenitor cell to mature multilineage neuronal cell maturation and its detailed molecular readout based on gene expression analysis, hNPT might have added value as a tool for neurodevelopmental toxicity testing in vitro. Further assessment of DNT-specific biomarkers that represent these processes needs further studies.
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