Human induced pluripotent stem cells for modelling neurodevelopmental disorders

Currently, we have a poor understanding of the pathogenesis of neurodevelopmental disorders, owing to the fact that post-mortem and imaging studies are only capable of measuring the postnatal status quo and offer little insight into the processes that give rise to the observed outcomes. Human induced pluripotent stem cells (hiPSCs) in principle should prove powerful in elucidating the pathways that give rise to neurodevelopmental disorders. HiPSCs are embryonic stem cell-like cells that can be derived from somatic cells. They retain the unique genetic signature of the individual from whom they were derived from, and thus allow researchers to recapitulate that individual’s idiosyncratic neural development in a dish. In the case of diseased individuals, we can reenact the disease-altered trajectory of brain development and examine how and why phenotypic and molecular abnormalities arise in these diseased brains. In this paper, we review various aspects of hiPSC biology and experimental design as well as discuss existing hiPSC models of neurodevelopmental disorders. As already shown by some studies discussed in this review, our hope is that iPSCs will illuminate the pathophysiology of developmental disorders of the CNS and lead to therapeutic avenues for the millions that today suffer from neurodevelopmental disorders.