Exploring human brain development and disease using assembloids.

How the human brain develops and what goes awry in neurological disorders represent two long-lasting questions in neuroscience. Owing to the limited access to primary human brain tissue, insights into these questions have been largely gained through animal models. However, there are fundamental differences between developing mouse and human brain, and neural organoids derived from human pluripotent stem cells (hPSCs) have recently emerged as a robust experimental system that mimics self-organizing and multicellular features of early human brain development. Controlled integration of multiple organoids into assembloids has begun to unravel principles of cell-cell interactions. Moreover, patient-derived or genetically engineered hPSCs provide opportunities to investigate phenotypic correlates of neurodevelopmental disorders and to develop therapeutic hypotheses. Here, we outline the advances in technologies that facilitate studies by using assembloids and summarize their applications in brain development and disease modeling. Lastly, we discuss the major roadblocks of the current system and potential solutions.