Evidence map›Paper›PMID 37591832›Full record

ArticleNature communications2023

One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids.

Maarten H Geurts, Shashank Gandhi, Matteo G Boretto, Ninouk Akkerman, Lucca L M Derks, Gijs van Son, Martina Celotti, Sarina Harshuk-Shabso, Flavia Peci, Harry Begthel and 7 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
7.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
  2. Building and regenerating intestines by manipulating intestinal stem cells.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  3. Review
  4. Review
  5. New developments and applications of human organoids.Nature reviews. Molecular cell biology · 2026
    Review
  6. Article
  7. Review
  8. Precision A3G base editors for disease modeling and correction.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
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  10. Article
  11. Review
  12. Review
  13. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 3 countries.

Maarten H Geurts *Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584 CT, Utrecht, the Netherlands. M.H.Geurts-6@prinsesmaximacentrum.nl.
Shashank Gandhi *Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584 CT, Utrecht, the Netherlands.
Matteo G Boretto *Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584 CT, Utrecht, the Netherlands.
Ninouk AkkermanHubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584 CT, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0003-0547-3993
Lucca L M DerksOncode Institute, 3521AL, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0001-9836-5558
Gijs van SonHubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584 CT, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0003-0572-3243
Martina CelottiHubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584 CT, Utrecht, the Netherlands.
Sarina Harshuk-ShabsoHubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584 CT, Utrecht, the Netherlands.
Flavia PeciOncode Institute, 3521AL, Utrecht, the Netherlands.
Harry BegthelHubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584 CT, Utrecht, the Netherlands.
Delilah HendriksHubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584 CT, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0003-1159-5946
Paul SchürmannHubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584 CT, Utrecht, the Netherlands.
Amanda Andersson-RolfHubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584 CT, Utrecht, the Netherlands.
Susana M Chuva de Sousa LopesAnatomy and Embryology, Leiden University Medical Center, Einthovenweg, 2333 ZC, Leiden, the Netherlands.
Johan H van EsHubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584 CT, Utrecht, the Netherlands.
Ruben van BoxtelOncode Institute, 3521AL, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0003-1285-2836
Hans CleversHubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584 CT, Utrecht, the Netherlands. h.clevers@hubrecht.eu.ORCID http://orcid.org/0000-0002-3077-5582
Royal Netherlands Academy of Arts and Sciences · NLOncode Institute · NLLeiden University Medical Center · NLNovartis (Switzerland) · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Optimization of CRISPR/Cas9-mediated genome engineering has resulted in base editors that hold promise for mutation repair and disease modeling. Here, we demonstrate the application of base editors for the generation of complex tumor models in human ASC-derived organoids. First we show efficacy of cytosine and adenine base editors in modeling CTNNB1 hot-spot mutations in hepatocyte organoids. Next, we use C > T base editors to insert nonsense mutations in PTEN in endometrial organoids and demonstrate tumorigenicity even in the heterozygous state. Moreover, drug sensitivity assays on organoids harboring either PTEN or PTEN and PIK3CA mutations reveal the mechanism underlying the initial stages of endometrial tumorigenesis. To further increase the scope of base editing we combine SpCas9 and SaCas9 for simultaneous C > T and A > G editing at individual target sites. Finally, we show that base editor multiplexing allow modeling of colorectal tumorigenesis in a single step by simultaneously transfecting sgRNAs targeting five cancer genes.

Indexed as

Adult Stem CellsRNA, Guide, CRISPR-Cas SystemsAdultCarcinogenesisCell Transformation, NeoplasticHumansOncogenesOrganoidsRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID37591832
PMCPMC10435570
OpenAlexW4385948407

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.