Human fetal brain self-organizes into long-term expanding organoids

Delilah Hendriks*, Anna Pagliaro, Francesco Andreatta, Ziliang Ma, Joey van Giessen, Simone Massalini, Carmen López-Iglesias, Gijs J.F. van Son, Jeff DeMartino, J. Mirjam A. Damen, Iris Zoutendijk, Nadzeya Staliarova, Annelien L. Bredenoord, Frank C.P. Holstege, Peter J. Peters, Thanasis Margaritis, Susana Chuva de Sousa Lopes, Wei Wu, Hans Clevers*, Benedetta Artegiani*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)
14 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)712-732.e38
Issue number3
Publication statusPublished - 1 Feb 2024

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