ArticlePloS one2018
Modeling APC mutagenesis and familial adenomatous polyposis using human iPS cells.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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.
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.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Redefining familial adenomatous polyposis: competition, cooperation, and the path to monoclonality.Familial cancer · 2025Review
- Comparative gastrointestinal organoid models across species: A Zoobiquity approach for precision medicine.Regenerative therapy · 2025Review
- Advancements in theFrontiers in toxicology · 2025Review
- Endoscopic Surveillance after (Procto)Colectomy with Gastrointestinal Reconstruction in Patients with Familial Adenomatous Polyposis (FAP)-Principles, Goals and Practical Aspects Based on 12 Years of Observation.Life (Basel, Switzerland) · 2024Article
- Altered lipid metabolism in APC-driven colorectal cancer: the potential for therapeutic intervention.Frontiers in oncology · 2024Review
- Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy.Molecular cancer · 2023Review
- Application of Induced Pluripotent Stem Cells in Malignant Solid Tumors.Stem cell reviews and reports · 2023Review
- Modeling human cancer predisposition syndromes using CRISPR/Cas9 in human cell line models.Genes, chromosomes & cancer · 2023Review
- Aggregation of cryopreserved mid-hindgut endoderm for more reliable and reproducible hPSC-derived small intestinal organoid generation.Stem cell reports · 2022Article
- From the Dish to the Real World: Modeling Interactions between the Gut and Microorganisms in Gut Organoids by Tailoring the Gut Milieu.International journal of stem cells · 2022Review
- Pluripotent Stem Cells: Cancer Study, Therapy, and Vaccination.Stem cell reviews and reports · 2021Review
- The Use of Stem Cell-Derived Organoids in Disease Modeling: An Update.International journal of molecular sciences · 2021Review
- hPSC-derived organoids: models of human development and disease.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Heterozygous APC germline mutations impart predisposition to colorectal cancer.Scientific reports · 2021Article
- Modeling cancer progression using human pluripotent stem cell-derived cells and organoids.Stem cell research · 2020Review
- Modeling endodermal organ development and diseases using human pluripotent stem cell-derived organoids.Journal of molecular cell biology · 2020Review
- Generation of mesenchyme free intestinal organoids from human induced pluripotent stem cells.Nature communications · 2020Article
- Review
- Constructing and Deconstructing Cancers using Human Pluripotent Stem Cells and Organoids.Cell stem cell · 2019Review
- Insights Into Human Development and Disease From Human Pluripotent Stem Cell Derived Intestinal Organoids.Frontiers in medicine · 2019Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in the gene Adenomatous Polyposis Coli or APC appear in most sporadic cases of colorectal cancer and it is the most frequent mutation causing hereditary Familial Adenomatous Polyposis. The detailed molecular mechanism by which APC mutations predispose to the development of colorectal cancer is not completely understood. This is in part due to the lack of accessibility to appropriate models that recapitulate the early events associated with APC mediated intestinal transformation. We have established a novel platform utilizing human induced Pluripotent Stem cells or iPSC from normal or FAP-specific APC mutant individuals and evaluated the effect of the mutation in the cells before and after differentiation into intestinal organoids. In order to minimize genetic background effects, we also established an isogenic platform using TALEN-mediated gene editing. Comparison of normal and APC mutant iPSC revealed a significant defect in cell identity and polarity due to the presence of APC in heterozygosity as well as chromosomal aberrations including abnormal anaphases and centrosome numbers. Importantly, upon specification into intestinal progeny, APC heterozygosity was responsible for a major change in the transcriptional identity of the cells with dysregulation of key signaling pathways, including metabolic reprogramming, abnormal lipid metabolism and intestinal-specific cadherin expression. In conclusion, we have developed a novel iPSC/intestinal model of APC mutagenesis and provide strong evidence that APC in heterozygosity imparts a clear phenotypic and molecular defect, affecting basic cellular functions and integrity, providing novel insights in the earlier events of APC-mediated tumorigenesis.
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Registered trials
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.