Automated high-throughput generation of human neural organoids

Differentiation of human induced pluripotent stem (hiPS) cells into three-dimensional neural organoids is already enabling access to key developmental processes in the human nervous system and offers an opportunity to model severe neurological disorders. Our laboratory has pioneered the use of instructive signals to derive regionalized neural organoids. Automation for high-throughput generation of these neural organoids could facilitate drug and genetic screening applications, especially if amenable to arrayed production. Here, we develop a platform relying on inexpensive equipment for automated, scalable, and arrayed maintenance of regionalized neural organoids. We utilize transcriptomic profiling and functional assays of neuronal activity to establish the reliability and reproducibility of this system. We further adapt the platform to generate organoids resembling distinct central nervous system domains involving a diversity of neuronal cell types. We anticipate that this easy to implement platform will have wide applications for functional genomic and pharmacological screens.