Sequential cancer mutations in cultured human intestinal stem cells
Open accessAbstract
Crypt stem cells represent the cells of origin for intestinal neoplasia. Both mouse and human intestinal stem cells can be cultured in medium containing the stem-cell-niche factors WNT, R-spondin, epidermal growth factor (EGF) and noggin over long time periods as epithelial organoids that remain genetically and phenotypically stable. Here we utilize CRISPR/Cas9 technology for targeted gene modification of four of the most commonly mutated colorectal cancer genes (APC, P53 (also known as TP53), KRAS and SMAD4) in cultured human intestinal stem cells. Mutant organoids can be selected by removing individual growth factors from the culture medium. Quadruple mutants grow independently of all stem-cell-niche factors and tolerate the presence of the P53 stabilizer nutlin-3. Upon xenotransplantation into mice, quadruple mutants grow as tumours with features of invasive carcinoma. Finally, combined loss of APC and P53 is sufficient for the appearance of extensive aneuploidy, a hallmark of tumour progression.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In normal conditions, addition of Nutlin3a to the medium causes activation of TP53 leading to cell death.
“In normal condition, the addition of Nutlin3a to the medium will cause the activation of TP53 leading to cell death.”
From Protocol to create isogenic disease models from adult stem cell-derived organoids using next-generation CRISPR tools (2024) · cites this paper as [32]
The Abstract (page unavailable) identifies nutlin-3 as a P53 stabilizer, supporting the claim that it affects TP53. Our copy does not state that adding it to normal culture medium causes cell death; it reports only that quadruple-mutant organoids tolerate its presence. (LLM, conf=0.78)
Experimental — accuracy not yet measuredOrganoids engineered with TP53 point mutation or knockout can grow in the presence of Nutlin3a.
“Similarly, organoids engineered with TP53 point mutation or KO can grow in the presence of Nutlin3a.”
From Protocol to create isogenic disease models from adult stem cell-derived organoids using next-generation CRISPR tools (2024) · cites this paper as [32]
The indexed Abstract says CRISPR/Cas9 was used to modify P53 (TP53) in human intestinal organoids and that quadruple-mutant organoids tolerated nutlin-3. It does not establish that organoids with either a TP53 point mutation or a TP53 knockout, considered separately, could grow in its presence. (LLM, conf=0.79)
Experimental — accuracy not yet measuredTP53 mutant organoids can be functionally selected for by addition of Nutlin-3 to the selection medium.
“TP53 mutant organoids can be functionally selected for by addition of the compound Nutlin-3 to the selection medium13,14”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [13]
The Abstract says the engineered organoids include TP53 mutations and that quadruple mutants tolerate the P53 stabilizer nutlin-3. It does not say that adding nutlin-3 to the medium functionally selects TP53-mutant organoids; it describes mutant-organoid selection by removing growth factors instead. (LLM, conf=0.79)
Experimental — accuracy not yet measuredTP53 mutants can be functionally selected by addition of Nutlin-3 to selection medium.
“TP53 mutants can be functionally selected by addition of the compound Nutlin-3 to the selection medium13,14.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [13]
The Abstract says that quadruple mutants, which include a TP53 mutation, tolerate nutlin-3. It does not say that adding nutlin-3 to the medium functionally selects TP53 mutants; the selection method it describes is removal of growth factors. (LLM, conf=0.79)
Experimental — accuracy not yet measuredWild-type organoids heavily rely on Wnt-3A in expansion medium for sustained growth, so APC mutants can be selected by removing Wnt from selection medium.
“Since wild-type organoids heavily rely on Wnt-3A in the expansion medium for sustained growth, APC mutants can be readily selected by removing Wnt from the “selection” medium13,14.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [13]
The indexed Abstract says intestinal organoids can be maintained in medium containing WNT, that APC was among the genes modified, and that mutant organoids can be selected by removing individual growth factors. It does not explicitly say that removing WNT selects APC mutants, or specify Wnt-3A and the claimed dependence of wild-type organoids on it. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Multiplexed gene-knockout by conventional CRISPR/Cas9-mediated NHEJ is very efficient and can be readily applied in organoids.
“Multiplexed gene-knockout by conventional CRISPR/Cas9-mediated NHEJ is very efficient and can be readily applied in organoids13,14,62.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [13]
The indexed Abstract (page not specified) reports CRISPR/Cas9 modification of four genes in cultured human intestinal stem cells and the resulting mutant organoids, supporting application in organoids. It does not establish that conventional NHEJ-mediated multiplexed knockout is very efficient; the paper describes the mutations as sequential. (LLM, conf=0.83)
Experimental — accuracy not yet measuredSeveral preclinical human transformation organoid models have been developed through sequential CRISPR modifications of single or multiple oncogenic loci.
“Several preclinical human transformation organoid models have been developed through sequential CRISPR modifications of single or multiple oncogenic loci9–13.”
From Large-scale CRISPR screening in primary human 3D gastric organoids enables comprehensive dissection of gene-drug interactions (2025) · cites this paper as [11]
CRISPR/Cas9 has emerged as an efficient strategy for genome engineering and has been successfully used in model systems, including organoids, to study tumorigenesis.
“CRISPR/Cas9 has emerged as an efficient strategy for genome engineering and has been successfully used in model systems, including organoids, to study tumorigenesis13–16.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [13]
Colorectal cancer follows a relatively ordered mutational process and can be efficiently modeled through progressive loss of niche factors in ASC-derived colon organoids.
“We again focused on colorectal cancer which follows a relatively ordered mutational process55 and can be efficiently modeled through progressive loss of niche factors in ASC-derived colon organoids13,14.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [13]
Introduction of oncogene activating mutations depends on inefficient HDR pathway and remains a challenge.
“However, introduction of oncogene activating mutations depends on the inefficient HDR pathway and remains a challenge13,14.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [13]
The indexed Abstract (no page given) reports CRISPR/Cas9 modification of KRAS and other colorectal cancer genes, but does not say that introducing activating mutations depends on HDR or is challenging. Searches for HDR, homology-directed repair, and inefficiency found no passage addressing that point in our copy. (LLM, conf=0.72)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607 · see citing works
Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339 · see citing works
Comprehensive molecular characterization of human colon and rectal cancer
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11252 · Cited by 8,499 · see citing works
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., et al. (2009) · Nature · doi:10.1038/nature07935 · Cited by 7,204 · see citing works
Self-citationIn Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2
Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., et al. (2004) · Science · doi:10.1126/science.1092472 · Cited by 4,661 · see citing works
Sato, T., Stange, D. E., Ferrante, M., Vries, R. G. J., van Es, J. H., van den Brink, S., van Houdt, W. J., Pronk, A., van Gorp, J., Siersema, P. D., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.07.050 · Cited by 3,753 · see citing works
Prospective Derivation of a Living Organoid Biobank of Colorectal Cancer Patients
van de Wetering, M., Francies, H. E., Francis, J. M., Bounova, G., Iorio, F., Pronk, A., van Houdt, W., van Gorp, J., Taylor-Weiner, A., Kester, L., et al. (2015) · Cell · doi:10.1016/j.cell.2015.03.053 · Cited by 2,408 · see citing works
Self-citationSchwank, G., Koo, B.-K., Sasselli, V., Dekkers, J. F., Heo, I., Demircan, T., Sasaki, N., Boymans, S., Cuppen, E., van der Ent, C. K., et al. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.11.002 · Cited by 1,424 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Modeling Development and Disease with Organoids
Clevers, H. (2016) · Cell · doi:10.1016/j.cell.2016.05.082 · Cited by 3,196 · see citing works
Self-citationBatlle, E., & Clevers, H. (2017) · Nature Medicine · doi:10.1038/nm.4409 · Cited by 2,769 · see citing works
Self-citationZhan, T., Rindtorff, N., & Boutros, M. (2017) · Oncogene · doi:10.1038/onc.2016.304 · Cited by 2,626 · see citing works
Human organoids: model systems for human biology and medicine
Kim, J., Koo, B.-K., & Knoblich, J. A. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0259-3 · Cited by 2,187 · see citing works
A living biobank of breast cancer organoids captures disease heterogeneity
Sachs, N., de Ligt, J., Kopper, O., Gogola, E., Bounova, G., Weeber, F., Balgobind, A. V., Wind, K., Gracanin, A., Begthel, H., et al. (2018) · Cell · doi:10.1016/j.cell.2017.11.010 · Cited by 1,973 · see citing works
Self-citationDrost, J., & Clevers, H. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0007-6 · Cited by 1,790 · see citing works
Self-citationOrganoids as an in vitro model of human development and disease
Fatehullah, A., Tan, S. H., & Barker, N. (2016) · Nature Cell Biology · doi:10.1038/ncb3312 · Cited by 1,508 · see citing works
Hofer, M., & Lutolf, M. P. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00279-y · Cited by 1,184 · see citing works
Long‐term expanding human airway organoids for disease modeling
Sachs, N., Papaspyropoulos, A., Zomer‐van Ommen, D. D., Heo, I., Böttinger, L., Klay, D., Weeber, F., Huelsz‐Prince, G., Iakobachvili, N., Amatngalim, G. D., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2018100300 · Cited by 1,082 · see citing works
Self-citationCancer modeling meets human organoid technology
Tuveson, D., & Clevers, H. (2019) · Science · doi:10.1126/science.aaw6985 · Cited by 935 · see citing works
Self-citationAn organoid platform for ovarian cancer captures intra- and interpatient heterogeneity
Kopper, O., de Witte, C. J., Lõhmussaar, K., Valle-Inclan, J. E., Hami, N., Kester, L., Balgobind, A. V., Korving, J., Proost, N., Begthel, H., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0422-6 · Cited by 834 · see citing works
Self-citationDisease modeling in stem cell-derived 3D organoid systems
Dutta, D., Heo, I., & Clevers, H. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.02.007 · Cited by 838 · see citing works
Self-citationThree-Dimensional Cell Cultures in Drug Discovery and Development
Fang, Y., & Eglen, R. M. (2017) · SLAS Discovery · doi:10.1177/1087057117696795 · Cited by 849 · see citing works
Mutational processes shape the landscape of TP53 mutations in human cancer
Giacomelli, A. O., Yang, X., Lintner, R. E., McFarland, J. M., Duby, M., Kim, J., Howard, T. P., Takeda, D. Y., Ly, S. H., Kim, E., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0204-y · Cited by 556 · see citing works
Tetteh, P. W., Basak, O., Farin, H. F., Wiebrands, K., Kretzschmar, K., Begthel, H., van den Born, M., Korving, J., de Sauvage, F., van Es, J. H., et al. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.01.001 · Cited by 575 · see citing works
Self-citationGenetics and Genetic Biomarkers in Sporadic Colorectal Cancer
Carethers, J. M., & Jung, B. H. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.06.047 · Cited by 483 · see citing works
Mutations and mechanisms of WNT pathway tumour suppressors in cancer
Bugter, J. M., Fenderico, N., & Maurice, M. M. (2021) · Nature Reviews Cancer · doi:10.1038/s41568-020-00307-z · Cited by 466 · see citing works
Xenograft and organoid model systems in cancer research
Bleijs, M., van de Wetering, M., Clevers, H., & Drost, J. (2019) · The EMBO Journal · doi:10.15252/embj.2019101654 · Cited by 400 · see citing works
Self-citationVitale, I., Manic, G., De Maria, R., Kroemer, G., & Galluzzi, L. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.04.006 · Cited by 361 · see citing works
Efficient genetic engineering of human intestinal organoids using electroporation
Fujii, M., Matano, M., Nanki, K., & Sato, T. (2015) · Nature Protocols · doi:10.1038/nprot.2015.088 · Cited by 364 · see citing works
Organoids in immunological research
Bar-Ephraim, Y. E., Kretzschmar, K., & Clevers, H. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0248-y · Cited by 361 · see citing works
Self-citationQi, Z., Li, Y., Zhao, B., Xu, C., Liu, Y., Li, H., Zhang, B., Wang, X., Yang, X., Xie, W., et al. (2017) · Nature Communications · doi:10.1038/ncomms13824 · Cited by 320 · see citing works
Targeting mutant RAS in patient-derived colorectal cancer organoids by combinatorial drug screening
Verissimo, C. S., Overmeer, R. M., Ponsioen, B., Drost, J., Mertens, S., Verlaan-Klink, I., Gerwen, B. V., van der Ven, M., Wetering, M. V. D., Egan, D. A., et al. (2016) · eLife · doi:10.7554/elife.18489 · Cited by 263 · see citing works
Self-citationMetastatic recurrence in colorectal cancer arises from residual EMP1+ cells
Cañellas-Socias, A., Cortina, C., Hernando-Momblona, X., Palomo-Ponce, S., Mulholland, E. J., Turon, G., Mateo, L., Conti, S., Roman, O., Sevillano, M., et al. (2022) · Nature · doi:10.1038/s41586-022-05402-9 · Cited by 256 · see citing works
Cell membrane coated-nanoparticles for cancer immunotherapy
Zeng, Y., Li, S., Zhang, S., Wang, L., Yuan, H., & Hu, F. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.02.023 · Cited by 238 · see citing works
Probing the Tumor Suppressor Function of BAP1 in CRISPR-Engineered Human Liver Organoids
Artegiani, B., van Voorthuijsen, L., Lindeboom, R. G. H., Seinstra, D., Heo, I., Tapia, P., López-Iglesias, C., Postrach, D., Dayton, T., Oka, R., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.04.017 · Cited by 218 · see citing works
Self-citationOrgan-on-a-Chip for Cancer and Immune Organs Modeling
Sun, W., Luo, Z., Lee, J., Kim, H., Lee, K., Tebon, P., Feng, Y., Dokmeci, M. R., Sengupta, S., & Khademhosseini, A. (2019) · Advanced Healthcare Materials · doi:10.1002/adhm.201801363 · Cited by 221 · see citing works
Applications of organoids for cancer biology and precision medicine
Lo, Y.-H., Karlsson, K., & Kuo, C. J. (2020) · Nature Cancer · doi:10.1038/s43018-020-0102-y · Cited by 182 · see citing works
α-Ketoglutarate attenuates Wnt signaling and drives differentiation in colorectal cancer
Tran, T. Q., Hanse, E. A., Habowski, A. N., Li, H., Ishak Gabra, M. B., Yang, Y., Lowman, X. H., Ooi, A. M., Liao, S. Y., Edwards, R. A., et al. (2020) · Nature Cancer · doi:10.1038/s43018-020-0035-5 · Cited by 161 · see citing works
Genomic instability, inflammatory signaling and response to cancer immunotherapy
Chen, M., Linstra, R., & van Vugt, M. A. T. M. (2022) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2021.188661 · Cited by 166 · see citing works
Organoids to model liver disease
Nuciforo, S., & Heim, M. H. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2020.100198 · Cited by 164 · see citing works
Next-Generation Surrogate Wnts Support Organoid Growth and Deconvolute Frizzled Pleiotropy In Vivo
Miao, Y., Ha, A., de Lau, W., Yuki, K., Santos, A. J. M., You, C., Geurts, M. H., Puschhof, J., Pleguezuelos-Manzano, C., Peng, W. C., et al. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.07.020 · Cited by 151 · see citing works
Self-citationTGFβ signaling directs serrated adenomas to the mesenchymal colorectal cancer subtype
Fessler, E., Drost, J., van Hooff, S. R., Linnekamp, J. F., Wang, X., Jansen, M., De Sousa E Melo, F., Prasetyanti, P. R., IJspeert, J. E., Franitza, M., et al. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606184 · Cited by 159 · see citing works
Self-citationRegulation of Wnt/β‐catenin signalling by tankyrase‐dependent poly(ADP‐ribosyl)ation and scaffolding
Mariotti, L., Pollock, K., & Guettler, S. (2017) · British Journal of Pharmacology · doi:10.1111/bph.14038 · Cited by 144 · see citing works
Sakai, E., Nakayama, M., Oshima, H., Kouyama, Y., Niida, A., Fujii, S., Ochiai, A., Nakayama, K. I., Mimori, K., Suzuki, Y., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-3303 · Cited by 133 · see citing works
Cancer research using organoid technology
Kretzschmar, K. (2021) · Journal of Molecular Medicine · doi:10.1007/s00109-020-01990-z · Cited by 120 · see citing works
Long-term expansion, genomic stability and in vivo safety of adult human pancreas organoids
Georgakopoulos, N., Prior, N., Angres, B., Mastrogiovanni, G., Cagan, A., Harrison, D., Hindley, C. J., Arnes-Benito, R., Liau, S.-S., Curd, A., et al. (2020) · BMC Developmental Biology · doi:10.1186/s12861-020-0209-5 · Cited by 112 · see citing works
Autophagy promotes mammalian survival by suppressing oxidative stress and p53
Yang, Y., Karsli-Uzunbas, G., Poillet-Perez, L., Sawant, A., Hu, Z. S., Zhao, Y., Moore, D., Hu, W., & White, E. (2020) · Genes & Development · doi:10.1101/gad.335570.119 · Cited by 100 · see citing works
Intestinal organoids: A new paradigm for engineering intestinal epithelium in vitro
Rahmani, S., Breyner, N. M., Su, H.-M., Verdu, E. F., & Didar, T. F. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2018.12.006 · Cited by 98 · see citing works
The potential of organoids in urological cancer research
Wang, S., Gao, D., & Chen, Y. (2017) · Nature Reviews Urology · doi:10.1038/nrurol.2017.65 · Cited by 87 · see citing works
Next-Generation Liver Medicine Using Organoid Models
Akbari, S., Arslan, N., Senturk, S., & Erdal, E. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00345 · Cited by 72 · see citing works
Ekert, J. E., Deakyne, J., Pribul-Allen, P., Terry, R., Schofield, C., Jeong, C. G., Storey, J., Mohamet, L., Francis, J., Naidoo, A., et al. (2020) · SLAS DISCOVERY · doi:10.1177/2472555220923332 · Cited by 68 · see citing works
One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids
Geurts, M. H., Gandhi, S., Boretto, M. G., Akkerman, N., Derks, L. L. M., van Son, G., Celotti, M., Harshuk-Shabso, S., Peci, F., Begthel, H., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40701-3 · Cited by 66 · see citing works
“Asdescribedearlierinthisstudy, TP53 mutants can be functionally selected by addition of the compound Nutlin-3 to the selection medium 13,14 .”
InfluentialSelf-citationPresent Application and Perspectives of Organoid Imaging Technology
Fei, K., Zhang, J., Yuan, J., & Xiao, P. (2022) · Bioengineering · doi:10.3390/bioengineering9030121 · Cited by 65 · see citing works
BCL-XL is crucial for progression through the adenoma-to-carcinoma sequence of colorectal cancer
Ramesh, P., Lannagan, T. R. M., Jackstadt, R., Atencia Taboada, L., Lansu, N., Wirapati, P., van Hooff, S. R., Dekker, D., Pritchard, J., Kirov, A. B., et al. (2021) · Cell Death & Differentiation · doi:10.1038/s41418-021-00816-w · Cited by 52 · see citing works
Self-citationPatient-derived tumor models: a more suitable tool for pre-clinical studies in colorectal cancer
Rizzo, G., Bertotti, A., Leto, S. M., & Vetrano, S. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01970-2 · Cited by 51 · see citing works
Genome engineering of stem cell organoids for disease modeling
Sun, Y., & Ding, Q. (2017) · Protein & Cell · doi:10.1007/s13238-016-0368-0 · Cited by 39 · see citing works
Lo, Y.-H., Horn, H. T., Huang, M.-F., Yu, W.-C., Young, C.-M., Liu, Q., Tomaske, M., Towers, M., Dominguez, A., Bassik, M. C., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-62818-3 · Cited by 37 · see citing works
“In contrast, only a few genes showed increased sgRNA abundance, indicating a growth advantage phenotype upon knockout (Supplementary Data 2).”
Influential2D- and 3D-Based Intestinal Stem Cell Cultures for Personalized Medicine
Liu, Y., & Chen, Y.-G. (2018) · Cells · doi:10.3390/cells7120225 · Cited by 37 · see citing works
Karyotypic Aberrations in Oncogenesis and Cancer Therapy
Vitale, I., Manic, G., Senovilla, L., Kroemer, G., & Galluzzi, L. (2015) · Trends in Cancer · doi:10.1016/j.trecan.2015.08.001 · Cited by 34 · see citing works
The Impact of Cancer Stem Cells in Colorectal Cancer
Radu, P., Zurzu, M., Tigora, A., Paic, V., Bratucu, M., Garofil, D., Surlin, V., Munteanu, A. C., Coman, I. S., Popa, F., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084140 · Cited by 30 · see citing works
Nanoblades allow high-level genome editing in murine and human organoids
Tiroille, V., Krug, A., Bokobza, E., Kahi, M., Bulcaen, M., Ensinck, M. M., Geurts, M. H., Hendriks, D., Vermeulen, F., Larbret, F., et al. (2023) · Molecular Therapy - Nucleic Acids · doi:10.1016/j.omtn.2023.06.004 · Cited by 25 · see citing works
Self-citationDijkstra, J. J., Neikes, H. K., Rezaeifard, S., Ma, X., Voest, E. E., Tauriello, D. V. F., & Vermeulen, M. (2023) · Journal of Proteome Research · doi:10.1021/acs.jproteome.2c00551 · Cited by 23 · see citing works
Efficient genetic editing of human intestinal organoids using ribonucleoprotein-based CRISPR
Skoufou-Papoutsaki, N., Adler, S., D'Santos, P., Mannion, L., Mehmed, S., Kemp, R., Smith, A., Perrone, F., Nayak, K., Russell, A., et al. (2023) · Disease Models & Mechanisms · doi:10.1242/dmm.050279 · Cited by 22 · see citing works
“Edited organoids have also been used for xenotransplantation approaches (Drost et al., 2015; Matano et al., 2015; Fumagalli et al., 2017).”
Küçükköse, E., Peters, N. A., Ubink, I., van Keulen, V. A. M., Daghighian, R., Verheem, A., Laoukili, J., & Kranenburg, O. (2022) · Cell Death & Disease · doi:10.1038/s41419-022-05078-z · Cited by 18 · see citing works
Celotti, M., Derks, L. L. M., van Es, J., van Boxtel, R., Clevers, H., & Geurts, M. H. (2024) · STAR Protocols · doi:10.1016/j.xpro.2024.103189 · Cited by 17 · see citing works
Self-citationConsensus molecular subtype transition during progression of colorectal cancer
van de Weerd, S., Torang, A., Zwager, L. W., Koelink, P. J., Koster, J., Bastiaansen, B. A., Lammers, V., Longobardi, C., Roodhart, J. M., van Krieken, J. H., et al. (2023) · The Journal of Pathology · doi:10.1002/path.6176 · Cited by 6 · see citing works
Self-citation
- Authors
- Drost, J., van Jaarsveld, R. H., Ponsioen, B., Zimberlin, C., van Boxtel, R., Buijs, A., Sachs, N., Overmeer, R. M., Offerhaus, G. J., Begthel, H., Korving, J., van de Wetering, M., Schwank, G., Logtenberg, M., Cuppen, E., Snippert, H. J., Medema, J. P., Kops, G. J. P. L., & Clevers, H.
- Affiliations
- Royal Netherlands Academy of Arts and Sciences (NL)
- University Medical Center Utrecht (NL)
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Clevers, Hans
- ORCID
- Venue
- Nature
- Published
- 2015-04-29
- Volume
- 521
- Issue
- 7550
- Pages
- 43-47
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2088245621
- Cited by
- 1,067
- References
- 8
- Citations by year
- 2026: 70 · 2025: 78 · 2024: 83 · 2023: 99 · 2022: 107 · 2021: 132 · 2020: 126 · 2019: 89 · 2018: 80 · 2017: 102 · 2016: 75 · 2015: 22
- FWCI
- 37.34
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- colorectal cancer, intestinal stem cells, organoids, tumor organoids, APC mutation, TP53 mutation, KRAS mutation, SMAD4 mutation, CRISPR/Cas9 genome editing, aneuploidy, tumor progression, xenotransplantation, stem cell niche, Nutlin-3, small intestine
- MeSH terms
- Aneuploidy, Animals, Child, Child, Preschool, Female, Humans, Imidazoles, Intestinal Mucosa, Intestines, Middle Aged, Mutation, Neoplasm Invasiveness, Neoplasm Transplantation, Organoids, Piperazines, Stem Cells, Colorectal Neoplasms, Genes, p53, Proto-Oncogene Proteins p21(ras), Mutagenesis, Site-Directed, Genes, APC, Intercellular Signaling Peptides and Proteins, Mice, Smad4 Protein, Stem Cell Niche, CRISPR-Cas Systems, Heterografts
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
