Effects of five developmental neurotoxicants on neuronal differentiation of human embryonic stem cell derived neural progenitors

Neuronal differentiation of human embryonic stem cells (hESC) is a promising tool to assess developmental neurotoxicity (DNT) in an animal-free manner. We analysed the transcriptomic profiles of hESC-derived neural progenitors (NPCs) and neuron-astrocyte co-cultures differentiated for 10 days from these same NPCs to identify the most dominant biological processes during neuronal differentiation. In addition, we exposed the NPCs for 10 days to five known or suspected neurodevelopmental toxicants: acrylamide, chlorpyrifos, fluoxetine, methyl mercury or valproic acid at non-cytotoxic (IC20/100) and slightly cytotoxic (IC5) levels. Each compound and concentration revealed unique transcriptomic changes that showed some of the known in vivo mechanisms of these compounds. This study provides evidence that this assay, the human neural progenitor test (hNPT) can be pivotal, together with other animal-free methods, to assess chemical-induced DNT in vitro. Overall design: mRNA profiles of human stem cell (H9)-derived neural progenitor cells and differentiated neuron-astrocyte co-cultures (day 10), and neuron-astrocyte co-cultures that were exposed to five compounds at two concentrations. N=1 and n=8 for all experimental conditions.