Pluripotent stem cell–derived brain-region-specific organoids

Abstract Brain organoids derived from human pluripotent stem cells have emerged as invaluable tools to study human-specific features in normal brain development and diseases. Given that brain regions differ in cellular composition, molecular signature, and functional specialization, establishing brain-region-specific organoids is crucial for more precise in vitro modeling of human brains. Here, we review selected protocols for generating brain organoids with various regional identities from pluripotent stem cells, including dorsal forebrain, ventral forebrain, hippocampus, thalamus, hypothalamus, retina, midbrain, and cerebellum. These organoids possess many characteristics that resemble the fetal brain tissue of the corresponding brain regions. In addition, we highlight the utilities of using these protocols in elucidating neurodevelopmental processes, studying the impacts of genetic and environmental perturbations, and facilitating strategic development of therapies.