Flora Vaccarino and her colleagues will take advantage of a technique for generating stem cells from skin biopsy samples. The technique reprograms skin cells into induced pluripotent stem (iPS) cells, which can then differentiate into any of the body's cell types, including neural stem cells. Vaccarino's team will obtain skin samples from participants in the Simons Simplex Collection. The researchers will derive iPS cell lines from people with autism and controls and induce the cells to differentiate into neuronal stem cells. Then, they will examine the cells for various phenotypic characteristics — such as morphology, surface marker expression, and messenger RNA (mRNA) expression. The researchers will also use techniques to look for changes in DNA as the neural stem cells differentiate, including variations in copy number and DNA methylation. The research team's stem cell studies will allow them to recapitulate the biological steps involved in the development of neurons, and observe how this process might be altered by autism-linked genetic variants. The study also aims to establish the validity of iPS cells as a tool for autism research by demonstrating that they can reproducibly give rise to brain neurons while maintaining the unique genetic traits of the people from whom they originate.