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In vitro differentiation of pluripotent stem cells provides a systematic platform to study development and disease. Recent advances in brain organoid technology have created new opportunities to investigate the formation and function of the human brain, under physiological and pathological conditions. Brain organoids can be generated to model the cellular and structural development of the human brain, and allow the investigation of the intricate interactions between resident neural and glial cell types. Combined with new advances in gene editing, imaging, and genomic analysis, brain organoid technology can be applied to address questions pertinent to human brain development, disease, and evolution. However, the current iterations of brain organoids also have limitations in faithfully recapitulating the in vivo processes. In this perspective, we evaluate the recent progress in brain organoid technology, and discuss the experimental considerations for its utilization. Dual Perspectives Companion Paper: Integrating CRISPR Engineering and hiPSC-Derived 2D Disease Modeling Systems, by Kristina Rehbach, Michael B. Fernando, and Kristen J. Brennand.

Studying Human Neurodevelopment and Diseases Using 3D Brain Organoids