Generation of Cerebral Organoids Derived from Human Pluripotent Stem Cells

Human cortical brain development is a tightly controlled and highly orchestrated process composed of neural progenitor cell (NPC) proliferation, migration, differentiation, and maturation. Recent advances in cerebral organoid technology have provided a means to model these complex cellular mechanisms to advance our understanding of normal human brain development and to provide molecular insight into the pathogenesis of brain disease. Cerebral organoids, which are generated from human pluripotent stem cells, are composed of three-dimensional neural tissue. This tissue can self-organize to form discrete regions of the human brain that includes cerebral cortex, choroid plexus, and others, if appropriate differentiation cues are present. Indeed, cerebral organoids provide an invaluable resource to study human-specific aspects of corticogenesis in vitro, such as investigating the function of outer radial glia (oRG), and other complex features of the human cerebral cortex. Here, we provide an overview of several methodologies to generate human cerebral organoids derived from human pluripotent stem cells including modifications from our laboratory. In addition, we highlight the advantages and current challenges associated with using cerebral organoids as an in vitro system to model human cortical brain development and disease.