Fig. 1.

A roadmap towards ASD modeling in hPSCs. Genomic analysis from ASD patients identifies those who harbor genetic defects that might be causal and hiPSCs from these patients can be generated from biopsy material. Insight into shared pathophysiological trajectories comes from pathway analyses of genetic aberrations, as well as from network-based analyses of gene expression in postmortem brains of ASD patients. Guided by the identification of pathways commonly dysregulated in larger subsets of patients, this knowledge informs the selection of genes to be targeted to create additional ASD models. If present in the patient cohort, these can be generated by somatic cell reprogramming. Alternatively, additional genotypes can be obtained from normal hPSCs via targeted genetic manipulation using genome editing. Control hPSCs may also be generated from patient hPSCs by reverting the causative genetic aberration using genome editing