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Searching for the origin of human brain tumours

In this Journal Club, Delilah Hendriks and Benedetta Artegiani recall a 2018 paper by Lee et al. that combined data from human patients and experimental model systems to reveal the complexities of how brain tumours originate.

Delilah Hendriks
Benedetta Artegiani
Research Highlights28 May 2025
Nature Reviews Genetics

Volume: 26, P: 511-512
Organoid models of fibrolamellar carcinoma mutations reveal hepatocyte transdifferentiation through cooperative BAP1 and PRKAR2A loss

An in-depth understanding of the molecular pathogenesis of fibrolamellar carcinoma (FLC) is hampered due to limited human preclinical models. Here the authors engineer human organoids to reflect different FLC genetic backgrounds and show that hepatocytes can be a cell-of-origin of FLC that transdifferentiate into ductal/progenitor like cells due to combined BAP1 and PRKAR2A loss.

Laura Rüland
Francesco Andreatta
Benedetta Artegiani
ResearchOpen Access03 May 2023
Nature Communications

Volume: 14, P: 1-20
Establishment of human fetal hepatocyte organoids and CRISPR–Cas9-based gene knockin and knockout in organoid cultures from human liver

Culture conditions are described for long-term expansion of human fetal hepatocytes as 3D organoids. Gene knockin and knockout approaches are also described for organoids derived from human fetal hepatocytes and human adult liver ductal cells.

Delilah Hendriks
Benedetta Artegiani
Hans Clevers
Protocols27 Nov 2020
Nature Protocols

Volume: 16, P: 182-217
Mapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth

Human hepatocytes remain hard to grow in vitro. Here, the authors temporally map the early stages of organoid growth initiated from fetal and adult hepatocytes, leveraging this knowledge to design maturation and improved expansion conditions.

Delilah Hendriks
Benedetta Artegiani
Hans Clevers
ResearchOpen Access13 May 2024
Nature Communications

Volume: 15, P: 1-15
Fast and efficient generation of knock-in human organoids using homology-independent CRISPR–Cas9 precision genome editing

Artegiani, Hendriks et al. describe a CRISPR–Cas9-based method to efficiently generate human knock-in organoids using non-homologous end joining to study rare intestinal cell types and human hepatocyte division.

Benedetta Artegiani
Delilah Hendriks
Hans Clevers
Research02 Mar 2020
Nature Cell Biology

Volume: 22, P: 321-331
Temporal morphogen gradient-driven neural induction shapes single expanded neuroepithelium brain organoids with enhanced cortical identity

PSC-brain organoids are typically formed by static medium switches. Here, authors show that a temporal morphogen gradient during neural induction allows the formation of well-specified cortical organoids with a self-organized single neuroepithelium.

Anna Pagliaro
Roxy Finger
Benedetta Artegiani
ResearchOpen Access28 Nov 2023
Nature Communications

Volume: 14, P: 1-16
Engineered human hepatocyte organoids enable CRISPR-based target discovery and drug screening for steatosis

Organoid models of early liver disease aid target discovery and drug screening.

Delilah Hendriks
Jos F. Brouwers
Hans Clevers
ResearchOpen Access23 Feb 2023
Nature Biotechnology

Volume: 41, P: 1567-1581
Author Correction: Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life

Gabriel Berdugo-Vega
Gonzalo Arias-Gil
Federico Calegari
Amendments and CorrectionsOpen Access25 Feb 2020
Nature Communications

Volume: 11, P: 1
Generation of human fetal brain organoids and their CRISPR engineering for brain tumor modeling

Establishment and robust expansion of human fetal brain organoids, their characterization and adaptation for downstream analyses, and how to genome engineer them to generate bottom-up brain tumor models.

Anna Pagliaro
Francesco Andreatta
Delilah Hendriks
Protocols06 Feb 2025
Nature Protocols

Volume: 20, P: 1846-1883
Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life

Ageing affects several brain areas causing a decrease in cognitive abilities and memory. We find that increasing the endogenous potential of the hippocampus to generate new neurons throughout life rejuvenates learning and memory, indicating that neural reserves can be exploited during ageing to compensate for age- or disease-related cognitive impairments.

Gabriel Berdugo-Vega
Gonzalo Arias-Gil
Federico Calegari
ResearchOpen Access09 Jan 2020
Nature Communications

Volume: 11, P: 1-12
Tubuloids derived from human adult kidney and urine for personalized disease modeling

‘Tubuloids’ grown from human kidney tissue and urine aid the study of BK virus infection, Wilms tumors and cystic fibrosis.

Frans Schutgens
Maarten B Rookmaaker
Hans Clevers
Research04 Mar 2019
Nature Biotechnology

Volume: 37, P: 303-313
Modelling Cryptosporidium infection in human small intestinal and lung organoids

The parasite Cryptosporidium can infect human organoids, where it replicates and completes its complex lifecycle. This new in vitro system enables the study of parasite development within the host and associated immune responses.

Inha Heo
Devanjali Dutta
Hans Clevers
Research25 Jun 2018
Nature Microbiology

Volume: 3, P: 814-823
Enteroendocrine cells switch hormone expression along the crypt-to-villus BMP signalling gradient

Beumer et al. show that intestinal enteroendocrine cells adjust their hormonal profile during migration from the crypt to the villus, depending on region-specific BMP signalling.

Joep Beumer
Benedetta Artegiani
Hans Clevers
Research23 Jul 2018
Nature Cell Biology

Volume: 20, P: 909-916
A comprehensive transcriptomic comparison of hepatocyte model systems improves selection of models for experimental use

A systematic comparison of transcriptomes across different hepatocyte models provides a valuable resource to determine the most suitable model for a particular application or research question.

Arif Ibrahim Ardisasmita
Imre F. Schene
Sabine A. Fuchs
ResearchOpen Access14 Oct 2022
Communications Biology

Volume: 5, P: 1-15

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Searching for the origin of human brain tumours

Organoid models of fibrolamellar carcinoma mutations reveal hepatocyte transdifferentiation through cooperative BAP1 and PRKAR2A loss

Establishment of human fetal hepatocyte organoids and CRISPR–Cas9-based gene knockin and knockout in organoid cultures from human liver

Mapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth

Fast and efficient generation of knock-in human organoids using homology-independent CRISPR–Cas9 precision genome editing

Temporal morphogen gradient-driven neural induction shapes single expanded neuroepithelium brain organoids with enhanced cortical identity

Engineered human hepatocyte organoids enable CRISPR-based target discovery and drug screening for steatosis

Author Correction: Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life

Generation of human fetal brain organoids and their CRISPR engineering for brain tumor modeling

Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life

Tubuloids derived from human adult kidney and urine for personalized disease modeling

Modelling Cryptosporidium infection in human small intestinal and lung organoids

Enteroendocrine cells switch hormone expression along the crypt-to-villus BMP signalling gradient

A comprehensive transcriptomic comparison of hepatocyte model systems improves selection of models for experimental use

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