Here, we present the generation of DG granule neurons from hPSCs and an in vitro model that recapitulates many of the features of the process of hippocampal neurogenesis. The ability to mimic the developmental process of disease-relevant cell types in an in vitro setting is important for providing insights into the generation and the pathogenesis of CNS disorders with a strong neurodevelopmental component. Our findings are relevant to studies of human in vitro hippocampal neurogenesis and represent a promising tool for the screening of drugs that could have clinical application in a disease setting.