Using iPS cells to study genetically defined patients with autism

Autism spectrum disorders are believed to have a strong genetic component, but little is known about how the mutations alter brain function and lead to the disorder’s symptoms. Research efforts have been stymied by the difficulty of studying neurons from people with autism in the laboratory. Ricardo Dolmetsch and his colleagues at Stanford University are tackling this issue using stem cells.

The researchers harvest skin cells from people with genetic forms of autism, then use viruses to convert these cells into induced pluripotent stem (iPS) cells. The recently developed iPS technology allows scientists to derive stem cells from adult cells, rather than embryos, and the resulting cells are capable of forming all other cells in the human body.

Dolmetsch’s team is using iPS cells to study the genetic and biochemical pathways that control the generation of the human brain — using cells from people with autism, rather than trying to replicate the genetic defects in mice. The researchers plan to examine the differentiation of iPS cells into neurons and glial cells, the main cell types in the human brain, and to characterize the cells’ function using a combination of microscopy, electrophysiology and cell biology.

The researchers aim to compare the mechanisms that generate brain cells in children with autism and in healthy controls, in the hopes of identifying specific aspects of neuronal differentiation and function that are altered in the affected children. The findings may shed light on the cellular and biochemical underpinnings of autism, and may help develop treatments for the disorder.