Murine cerebral organoids develop network of functional neurons and hippocampal brain region identity

• DOI: 10.1016/j.isci.2021.103438
• Publication Date: 2021-11-15T17:07:53Z
• Authors: Francesca Ciarpella; Raluca Georgiana ...; Alessandra Campan...; Elisa Ren; Giulia Pedrotti; Emanuela Bottani; Andrea Borioli; Davide Caron; Marzia Di Chio; Sissi Dolci; Annika Ahtiainen; Giorgio Malpeli; Giovanni Malerba; Rita Bardoni; Guido Fumagalli; Jari Hyttinen; Francesco Bifari; Gemma Palazzolo; Gabriella Panuccio; Giulia Curia; Ilaria Decimo
• Keywords: 570; Cell biology; 0303 health sciences; Biological sciences; Cell biology; Developmental biology; Neuroscience;; biological sciences; Science; Q; 610; 3111; Article; neuroscience; developmental biology; Biological sciences; 03 medical and health sciences; cell biology; Developmental biology; Biological sciences; Cell biology; Developmental biology; Neuroscience; 3111 Biomedicine; Neuroscience

Brain organoids are in vitro three-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 3D in vitro brain model that may represent a useful tool for high-throughput drug screening and disease modeling.