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

Francesca Ciarpella, Raluca Georgiana Zamfir, Alessandra Campanelli, 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 CuriaIlaria Decimo

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Abstract

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.

Original languageEnglish
Article number103438
JournalIscience
Volume24
Issue number12
DOIs
Publication statusPublished - 17 Dec 2021
Publication typeA1 Journal article-refereed

Keywords

  • Biological sciences
  • Cell biology
  • Developmental biology
  • Neuroscience

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • General

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