To address these problems, we here developed approaches that allow rapid and reproducible production of human iN cells from ES or iPS cells. The experiments we describe utilize a renewable resource and are scalable, and result in iN cells with reproducible properties that are independent of the starting ES or iPS cell line. Strikingly, our approach requires only a single transcription factor, and generates large amounts of human iN cells with robust synapse formation capabilities. Moreover, we demonstrate that the resulting iN cells can be used for analysis of human neuronal short-term plasticity, large-scale Ca2+-imaging, or analysis of loss-of-function states mimicking a human genetic disorder. Thus, the approach we describe may be generally useful not only to explore the cellular phenotype associated with neuropsychiatric disorders, but also for drug screening endeavors and for mechanistic studies.
