2. Academic Validation
  3. Human fetal brain self-organizes into long-term expanding organoids

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

  • Cell. 2024 Jan 4:S0092-8674(23)01344-2. doi: 10.1016/j.cell.2023.12.012.
Delilah Hendriks 1,  Anna Pagliaro 2,  Francesco Andreatta 2,  Ziliang Ma 3,  Joey van Giessen 2,  Simone Massalini 2,  Carmen López-Iglesias 4,  Gijs J F van Son 5,  Jeff DeMartino 2,  J Mirjam A Damen 6,  Iris Zoutendijk 2,  Nadzeya Staliarova 6,  Annelien L Bredenoord 7,  Frank C P Holstege 8,  Peter J Peters 4,  Thanasis Margaritis 2,  Susana Chuva de Sousa Lopes 9,  Wei Wu 3,  Hans Clevers 10,  Benedetta Artegiani 11
Affiliations

Affiliations

  • 1 Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), Utrecht, the Netherlands; Oncode Institute, Utrecht, the Netherlands. Electronic address: [email protected].
  • 2 Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
  • 3 Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Immunos, Singapore 138648, Singapore; Department of Pharmacy, National University of Singapore, Singapore 117543, Singapore.
  • 4 The Maastricht Multimodal Molecular Imaging Institute, Maastricht University, Maastricht, the Netherlands.
  • 5 Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Oncode Institute, Utrecht, the Netherlands.
  • 6 Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.
  • 7 Erasmus School of Philosophy, Erasmus University Rotterdam, Rotterdam, the Netherlands.
  • 8 Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Center for Molecular Medicine, University Medical Center Utrecht and Utrecht University, Utrecht, the Netherlands.
  • 9 Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, the Netherlands.
  • 10 Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), Utrecht, the Netherlands; Oncode Institute, Utrecht, the Netherlands. Electronic address: [email protected].
  • 11 Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. Electronic address: [email protected].
PMID: 38194967 DOI: 10.1016/j.cell.2023.12.012
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.

Keywords

CRISPR-Cas9; ECM; brain cancer; brain development; human fetal brain; morphogens; organoids; regional identity; tissue culture; tumor modeling.

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