Evidence map›Paper›PMID 40813572›Full record

ArticleNature communications2025

Large-scale CRISPR screening in primary human 3D gastric organoids enables comprehensive dissection of gene-drug interactions.

Yuan-Hung Lo, Hudson T Horn, Mo-Fan Huang, Wei-Chieh Yu, Chia-Mei Young, Qing Liu, Madeline Tomaske, Martina Towers, Antonia Dominguez, Michael C Bassik and 5 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
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

22 citing papers in PubMed.

  1. Review
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  15. Stem Cells in Aging and Anti-Aging.Stem cell reviews and reports · 2026
    Review
  16. Review
  17. Review
  18. Organoids glimpse: the nexus for diverse tumor heterogeneity.Frontiers in cell and developmental biology · 2026
    Review
  19. Review
  20. Review
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

15 authors.

Yuan-Hung LoDepartment of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. ylo1@mdanderson.org.ORCID http://orcid.org/0000-0002-9704-3124
Hudson T HornDivision of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Mo-Fan HuangThe University of Texas MD Anderson Cancer Center, UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA.ORCID http://orcid.org/0000-0002-2209-1236
Wei-Chieh YuDepartment of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-6844-4845
Chia-Mei YoungDepartment of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0009-0002-8846-2340
Qing LiuDepartment of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Madeline TomaskeDivision of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Martina TowersDepartment of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Antonia DominguezDepartment of Bioengineering, Stanford University, Stanford, CA, USA.
Michael C BassikDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-5185-8427
Dung-Fang LeeThe University of Texas MD Anderson Cancer Center, UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA.ORCID http://orcid.org/0000-0003-2387-597X
Lei S QiDepartment of Bioengineering, Stanford University, Stanford, CA, USA.
Jonathan S WeissmanDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-2445-670X
Jin ChenLaboratory of Functional Genomics and Translational Control, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA. jchen@altoslabs.com.ORCID http://orcid.org/0000-0002-6634-4397
Calvin J KuoDivision of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. cjkuo@stanford.edu.ORCID http://orcid.org/0000-0002-7427-5985

Funding

Functional characterization of novel oncogenic loci driving progression and immune response in gastrointestinal cancerR00CA263014 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LO, YUAN-HUNG · 2023 to 2025
$747k
Functional characterization of novel oncogenic loci driving progression and immune response in gastrointestinal cancerK99CA263014 · NCI · STANFORD UNIVERSITY · PI LO, YUAN-HUNG · 2021 to 2022
$343k
NCI NIH HHS K99 CA263014NCI NIH HHS R00 CA263014
6 · The paper itself

Abstract

Understanding how genes influence drug responses is critical for advancing personalized cancer treatments. However, identifying these gene-drug interactions in a physiologically relevant human system remains a challenge, as it requires a model that reflects the complexity and heterogeneity among individuals. Here we show that large-scale CRISPR-based genetic screens, including knockout, interference (CRISPRi), activation (CRISPRa), and single-cell approaches, can be applied in primary human 3D gastric organoids to systematically identify genes that affect sensitivity to cisplatin. Our screens uncover genes that modulate cisplatin response. By combining CRISPR perturbations with single-cell transcriptomics, we resolve how genetic alterations interact with cisplatin at the level of individual cells and uncover an unexpected link between fucosylation and cisplatin sensitivity. We identify TAF6L as a regulator of cell recovery from cisplatin-induced cytotoxicity. These results highlight the utility of human organoid models for dissecting gene-drug interactions and offer insights into therapeutic vulnerabilities in gastric cancer.

Indexed as

CisplatinCRISPR-Cas SystemsOrganoidsStomachStomach NeoplasmsAntineoplastic AgentsHumansSingle-Cell AnalysisAntineoplastic AgentsCisplatin

Identifiers

PMID40813572
PMCPMC12354852

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.