The brain consists of two main types of cells, neurons and glia. Although neurons have been extensively studied, the contribution of glial cells to autism is not well understood. To address this deficit in knowledge, Erik Ullian and his colleagues proposed to investigate the developmental profile and functional properties of a special type of glial cell called an oligodendrocyte (OC), a specialized cell that enwraps axons with an insulating sheath that is essential for proper brain function and the transmission of signals among brain regions.
The researchers derived OCs from people with copy number variations (duplications or deletions of stretches of DNA) in chromosomal region 16p11.2. They hypothesized that both 16p11.2 deletion and duplication lead to modified maturation of oligodendrocyte progenitor cells (OPCs), the cells that ultimately mature into the myelinating OCs. Any such differences in maturation would likely lead to abnormal myelination of mature OCs.
To investigate this hypothesis, the researchers generated OPCs from human induced pluripotent stem (iPS) cells. This allowed them to generate OPCs that differentiated into OCs both from individuals with autism and 16p11.2 deletion, and from control groups. Ullian and his group set up assays to assess alterations in proliferation, gene expression, development and myelination potential of OPCs and OCs. Their studies suggest that OPCs from individuals with 16p11.2 deletion proliferate and mature more quickly than in controls, possibly leading to differences in myelination potential.
These studies will be among the first to investigate myelination impairments of autism using human-derived cells and among the first to explore OC contributions to autism.