1. Human fetal brain self-organizes into long-term expanding organoids.
- Author
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Hendriks D, Pagliaro A, Andreatta F, Ma Z, van Giessen J, Massalini S, López-Iglesias C, van Son GJF, DeMartino J, Damen JMA, Zoutendijk I, Staliarova N, Bredenoord AL, Holstege FCP, Peters PJ, Margaritis T, Chuva de Sousa Lopes S, Wu W, Clevers H, and Artegiani B
- Subjects
- Humans, Central Nervous System metabolism, Extracellular Matrix metabolism, Pluripotent Stem Cells metabolism, Prosencephalon cytology, Tissue Culture Techniques, Stem Cells metabolism, Morphogenesis, Brain cytology, Brain growth & development, Brain metabolism, Organoids
- Abstract
Human brain development involves an orchestrated, massive neural progenitor expansion while a multi-cellular tissue architecture is established. Continuously expanding organoids can be grown directly from multiple somatic tissues, yet to date, brain organoids can solely be established from pluripotent stem cells. Here, we show that healthy human fetal brain in vitro self-organizes into organoids (FeBOs), phenocopying aspects of in vivo cellular heterogeneity and complex organization. FeBOs can be expanded over long time periods. FeBO growth requires maintenance of tissue integrity, which ensures production of a tissue-like extracellular matrix (ECM) niche, ultimately endowing FeBO expansion. FeBO lines derived from different areas of the central nervous system (CNS), including dorsal and ventral forebrain, preserve their regional identity and allow to probe aspects of positional identity. Using CRISPR-Cas9, we showcase the generation of syngeneic mutant FeBO lines for the study of brain cancer. Taken together, FeBOs constitute a complementary CNS organoid platform., Competing Interests: Declaration of interests D.H., B.A., and H.C. are inventors on a patent related to this work. The full disclosure of H.C. is given at https://www.uu.nl/staff/JCClevers/., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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