To realize the full potential of hPSC technology, it is critical to efficiently generate homogeneous populations of specific differentiated progenies, as hPSC differentiation tends to be heterogeneous and stochastic [13]. In this study, employing stepwise regulation of developmentally relevant signaling pathways that recapitulates in vivo embryonic development, we established a differentiation method that allowed highly efficient and homogeneous differentiation of hPSCs to MGE cells or CGE cells and then to GABAergic interneurons. Recent studies have shown the potential of GABAergic interneurons as sources for novel cellular therapies for epilepsy [28,29], Parkinson’s disease [30], schizophrenia [31] and injury-induced neuropathic pain [32], yet optimal cell sources for such therapies are limiting. Therefore, the generation of a homogeneous population of GABAergic interneurons from hPSCs is an important step towards clinical translation of this experimental therapeutics. Furthermore, iPSC technology offers the potential to create disease models in a dish, thus facilitating disease mechanistic studies from human disease neurons, again, as long as disease-specific neuronal subtypes can be generated at high efficiency. This method for generating specific subtypes of GABAergic interneurons will play a pivotal role in reliable disease modeling of interneuron-associated diseases, such as epilepsy, autism and schizophrenia [11].
