Brain organoids: building higher-order complexity and neural circuitry models

Brain organoids are 3D tissue models of the human brain that are derived from pluripotent stem cells (PSCs). They have enabled studies that were previously stymied by the inaccessibility of human brain tissue or the limitations of mouse models of some brain diseases. Despite their enormous potential, brain organoids have had significant limitations that prevented them from recapitulating the full complexity of the human brain and reduced their utility in disease studies. We describe recent progress in addressing these limitations, especially building complex organoids that recapitulate the interactions between multiple brain regions, and reconstructing in vitro the neural circuitry present in vivo. These major advances in the human brain organoid technology will remarkably facilitate brain disease modeling and neuroscience research.