Flora Vaccarino and her colleagues at Yale University have developed and characterized several lines of human induced pluripotent stem (iPS) cells from the skin cells of two individuals with autism and their family members, all from the Simons Simplex Collection. These two individuals show a larger-than-normal head circumference.

The researchers used two neuronal differentiation protocols on these stem cells. One is a three-dimensional model that enables the investigators to study cortical layer formation and cell-to-cell communication during development of the cortex¹. The second allows for high-resolution study of neuron size, morphology and electrophysiological activity. Both preparations are being used in ongoing studies comparing the affected individuals and their unaffected family members in biological, molecular and genetic aspects of neurodevelopment.

In parallel, Vaccarino’s group has analyzed copy number variations (CNVs) — deletions or duplications of DNA — in the iPS cell genomes and compared them with those found in the original skin cell genomes. Whole-genome, high-throughput sequencing revealed an average of two CNVs per iPS cell line that were not present in the fibroblast cells from which the cells were derived. Only a minority of CNVs appeared to have been acquired during the reprogramming process. Therefore, reprogramming somatic cells into iPS cells does not necessarily induce de novo mutations².

Lastly, the researchers have begun to compare gene expression (via RNA sequencing) in iPS cells derived from affected individuals and their family members. The results suggest that the affected individuals’ iPS cells significantly differ from those of their unaffected family members in terms of gene sets involved in DNA repair, cell proliferation and embryonic development.