摘要：SummaryBrain organoids arein vitrothree-dimensional (3D) self-organized neural structures, which can enable disease modeling and drug screening. However, their use for standardized large-scale drug screening studies is limited by their high batch-to-batch variability, long differentiation time (10–20 weeks), and high production costs. This is particularly relevant when brain organoids are obtained from human induced pluripotent stem cells (iPSCs). Here, we developed, for the first time, a highly standardized, reproducible, and fast (5 weeks) murine brain organoid model starting from embryonic neural stem cells. We obtained brain organoids, which progressively differentiated and self-organized into 3D networks of functional neurons with dorsal forebrain phenotype. Furthermore, by adding the morphogen WNT3a, we generated brain organoids with specific hippocampal region identity. Overall, our results showed the establishment of a fast, robust and reproducible murine 3Din vitrobrain model that may represent a useful tool for high-throughput drug screening and disease modeling.Graphical abstractDisplay OmittedHighlights•Murine embryonic NSCs are able to self-organize into brain organoids•Murine brain organoids mature in 32 days, showing dorsal forebrain identity•Brain organoids develop 3D network of functional neurons•WNT3a supplementation induces specific hippocampal brain region identityBiological sciences; Neuroscience; Cell biology; Developmental biology
