Prospects for modeling abnormal neuronal function in schizophrenia using human induced pluripotent stem cells

Abstract

Excitatory dopaminergic neurons, inhibitory GABAergic neurons, microglia, and oligodendrocytes have all been implicated in schizophrenia (SZ) network pathology. Still, SZ has been a difficult disorder to study, not only because of the limitations of animal models in capturing the complexity of the human mind, but also because it is greatly polygenic, with high rates of variability across the population. The advent of patient-derived pluripotent stem cells and induced neural and glial cultures has brought hope for modeling the molecular dysfunction underlying SZ pathology in a patientspecific manner. Here I review the successes of the patient-specific induced cultures in generating different cell types for the study of SZ, with special emphasis on the utility of co-culture techniques, both two- and three-dimensional, for modeling network dysfunction in disease.