This study presents the human neural progenitor test (hNPT), a 10-day protocol in which neural progenitor cells differentiate into a neuron-astrocyte co-culture. The aim of the investigation was to characterise differentiation over time and to find neurodevelopmental processes sensitive to compound exposure using transcriptomics. Exposure to compounds with known or suspected developmental neurotoxicity regulated unique combinations of gene ontology (GO)-terms relating to neural progenitor proliferation, neuronal and glial differentiation, axon development, synaptogenesis, synaptic transmission, and apoptosis. Investigation of the GO-terms revealed common genes that were responsive across compounds and might be used as biomarkers for developmental neurotoxicity, while other GO-terms may articulate compound-specific effects that may be relevant for revealing mechanisms of toxicity. Due to its detailed molecular readout based on gene expression analysis, hNPT might have added value for neurodevelopmental toxicity testing in vitro.
Neuronal differentiation pathways and compound-induced developmental neurotoxicity in the human neural progenitor cell test (hNPT) revealed by RNA-seq
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