A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Winter, 2019 | Number 1, Volume 33

Stem cells offer clues about early neural development in ASD

Researchers at the Salk Institute report that stem cells derived from the skin cells of individuals with autism spectrum disorders (ASD) develop in a different pattern and at different speeds compared to stem cells created from the skin cells of individuals without ASD.

Simon Schafer and colleagues took skin cells from eight people with ASD and five controls and transformed them into pluripotent stem cells, which have the ability to develop into any type of cell. The researchers then chemically induced the cells to develop into neurons.

Using molecular “snapshots” from various stages during this process, the researchers tracked genetic programs that switched on as the stem cells developed into neurons. They found that the cells from individuals with ASD developed differently than the cells from controls. For instance, the genetic program associated with the neural stem-cell stage turned on earlier in the cells of individuals with ASD than it did in cells from controls. This program includes many genes associated with an increased risk for ASD. In addition, the neurons that developed from the stem cells of individuals with ASD grew faster and had more complex branches than those from controls.

Schafer comments, “It’s currently hypothesized that abnormalities in early brain development lead to autism, but the transition from a normally developing brain to an ASD diagnosis is blurred. A major challenge in the field has been to determine the critical developmental periods and their associated cellular states. This research could provide a basis for discovering the common pathological traits that emerge during ASD development.”

The researchers plan to extend their investigation by developing three-dimensional brain organoids to study the interactions between different brain cell types.


Citations

“Pathological priming causes developmental gene network heterochronicity in autistic subject derived neurons,” S. T. Schafer, A. C. M. Paquola, S. Stern, D. Gosselin, M. Ku, M. Pena, T. J. M. Kuret, M. Liyanage, A. A. Mansour, B. N. Jaeger, M. C. Marchetto, C. K. Glass, J. Mertens, and F. H. Gage, Nature Neuroscience, January 7, 2019 (epub prior to print publication). Address: Fred H. Gage, Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA, [email protected].

—and—

“Salk team reveals clues into early development of autism spectrum disorder,” news release, Salk Institute, January 7, 2019.