Stem cell-derived in vitro models of human cerebellar development

Understanding human cerebellar development and pathology remains challenging due to its complexity, unique protracted developmental timeline, and notable species-specific differences. Advances in human stem cell technologies have opened new windows of opportunity for exploring these processes through improved in vitro models, providing insights into human-specific mechanisms that traditional animal models may fail to recapitulate. Here, we review recent advancements in modelling physiological and pathological processes of human cerebellar development. We first outline key features of cerebellar development with an emphasis on human-specific aspects. We then systematically summarize and evaluate various strategies for generating human stem cell-derived cerebellar models in vitro, starting with foundational studies using mouse embryonic stem cells, followed by methods using human pluripotent stem cells to generate cerebellar cells in two-dimensional cultures and three-dimensional cerebellar organoids. Subsequently, we review the application of these models to study cerebellar diseases, highlighting translational opportunities and critical challenges that remain.