The Development of a High-Throughput Assay to Screen Chemical Compounds in Human Pluripotent Stem Cell Derived Neural Cells



 DESCRIPTION (provided by applicant): The long-term objective of this application is to provide a high-throughput platform to test the effects of chemical exposure on human brain development. In the US, chemicals are not required for health or environmental safety testing before their incorporation in consumer products. Over 80,000 registered chemicals are in commerce, most of which are used without any information on their long-term health effects. Considering each one of these one by one is a slow and expensive process. Currently there is no system in place to screen compounds in terms of their health consequences before product implementation and with over 80,000 registered chemicals in commerce, a high-throughput mechanism to screen these compounds is needed. Human pluripotent stem cell (hPSC) technology offers a manipulatable platform to study the early stages of brain development. In a recent study from our lab, we adapted a protocol to differentiate hPSCs into cerebral cortical neurons over 77 days that recapitulated each stage of cortical development. The cerebral cortex has been shown to be particularly sensitive to chemical exposure during development. Preliminary data from our lab show that chemical exposure during the early stages of this protocol lead to changes of key neuro- developmental genes at different times during development providing evidence that our in vitro system can be used to assess chemical toxicity. Here we propose the development of a high-throughput assay using hPSC technology to screen large numbers of chemical compounds by assessing how they alter human brain development. This study will develop a cost-effective tool to analyze thousands of compounds with a simple PCR assay that can be easily adapted and used by researchers and industries everywhere.