The Autism Center of Excellence is conducting studies of a special type of stem cell called human induced pluripotent stem cells (hiPSC cells), which are derived from the skin of living autistic children and adults. These studies aim to shed light on the underlying genetic, molecular and neural mechanisms of the disorder.
The ACE plans to use hiPSC cells to help understand the mechanisms that may underlie early brain over growth as well as the mechanisms that distinguish ASD children with good clinical outcomes from those with poor outcomes.
Leading this research are ACE Director Eric Courchesne, stem cell world leader Fred Gage from the Salk Institute for Biological Studies, and co-investigator Alysson Muotri.
Generating Neurons in the Lab from ASD Patients
In 2006, scientists in Japan discovered that skin cells could be changed (“reprogrammed”) into stem cells that are capable of making every type of cell found in the body, including brain cells.
This means that from just a tiny skin sample from our ASD patients, we can generate limitless brain cells (neurons) with which to study this disorder. Also, by taking skin samples from both patients with ASD and without, we can determine how the brain cells from the ASD patients are different.
We hope that understanding how brain cells with ASD are different will help us eventually identify drugs that help reverse these effects.
hiPSC derived brain cells from ASD patients may have too few or too many connections
From our hiPSCs, we can generate brain cells from patients with ASD. By taking extremely high magnification images (up to 1200x magnification) we can count the number of connections between brain cells and see if this is affected in ASD.
Above: Neurons differentiated from hiPSCs from a patient with ASD. The axons of the neurons are labeled in green, the dendrites are labeled in red and the nuclei in blue. 100x magnification. Image courtesy of Fred Gage Laboratory.
hiPSC derived brain cells from ASD patients may undergo too much replication during maturation
Eric Courchesne and ACE colleagues have already shown that the majority of autistic children have brain volumes larger than the normal average by 2 to 4 years of age based on both MRI (Courchesne et al., 2001) and head circumference data (Courchesne et al., 2003). This brain size increase coincides with the onset of autistic symptoms but occurs through an unknown mechanism.
The ACE stem cell team will test whether there is excessive cellular replication as hiPSCs from ASD patients are differentiated into neurons in the laboratory.
hiPSC derived brain cells from ASD patients may have aberrant activity by some genes. Every feature and function of a cell is regulated by the expression of genes. By understanding which genes are undergoing aberrant expression in neurons from these patients, we may come to better understand what causes ASD.
By generating large numbers of living human control and ASD neurons, we can complete experiments to determine which genes, if any, show abnormal expression (either too high or too low) in ASD.