?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.
Public Health Relevance Statement: Public Health Relevance: Many classes of chemicals found in consumer products contribute to chronic health problems in our population. In particular, evidence has emerged in the last 5 years showing significant effects of chemical exposure on brain development. This study aims to create a novel platform to test the effects of chemical exposure on human brain development using stem cell technology allowing for the systematic testing of chemicals before product implementation.
NIH Spending Category: Biotechnology; Neurosciences; Regenerative Medicine; Stem Cell Research; Stem Cell Research - Embryonic - Human
Project Terms: Affect; autism spectrum disorder; Biological Assay; Biological Testing; Brain; Cell Line; Cerebral cortex; Cerebrum; Chemical Exposure; Chemicals; Chronic; Commerce; consumer product; cost effective; Data; Development; Developmental Gene; disability; Exposure to; Gene Expression; Health; high throughput screening; Human; Human Development; human embryonic stem cell; In Vitro; induced pluripotent stem cell; Industry; Laboratories; Lead; Malignant Neoplasms; Nature; Neurons; novel; Pluripotent Stem Cells; Population; Process; Production; Protocols documentation; Psyche structure; public health relevance; Research Personnel; safety testing; Staging; stem cell technology; System; Testing; Time; tool; Toxic effect; transcriptomics; United States
