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

iScience

Annika Ahtiainen¹  Jari Hyttinen¹  Elisa Ren²  Giulia Curia²  Rita Bardoni²  Davide Caron³  Gemma Palazzolo³  Gabriella Panuccio³  Giovanni Malerba⁴  Giorgio Malpeli⁵  Francesco Bifari⁶  Ilaria Decimo⁷  Emanuela Bottani⁷  Guido Fumagalli⁷  Marzia Di Chio⁷  Giulia Pedrotti⁷  Francesca Ciarpella⁷  Raluca Georgiana Zamfir⁷  Alessandra Campanelli⁷  Andrea Borioli⁷  Sissi Dolci⁷ 

[1] BioMediTech, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland;Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy;Department of Neuroscience and Brain Technologies (NBT), Istituto Italiano di Tecnologia (IIT), Genova, Italy;Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy;Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37134 Verona, Italy;Laboratory of Cell Metabolism and Regenerative Medicine, Department of Medical Biotechnology and Translational Medicine, University of Milan, 20133 Milan, Italy;Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy;

关键词: Biological sciences;    Neuroscience;    Cell biology;    Developmental biology;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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.

【 授权许可】

Unknown