Evidence map›Paper›PMID 30024920›Full record

ArticlePloS one2018

Modeling APC mutagenesis and familial adenomatous polyposis using human iPS cells.

Cesar A Sommer, Amalia Capilla, Francisco J Molina-Estevez, Andreia Gianotti-Sommer, Nicholas Skvir, Ignacio Caballero, Sanjib Chowdhury, Gustavo Mostoslavsky

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

24 citing papers in PubMed, 36 citations in OpenAlex.

  1. Review
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  3. Advancements in theFrontiers in toxicology · 2025
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  12. The Use of Stem Cell-Derived Organoids in Disease Modeling: An Update.International journal of molecular sciences · 2021
    Review
  13. hPSC-derived organoids: models of human development and disease.Journal of molecular medicine (Berlin, Germany) · 2021
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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

8 authors at 1 institution in 1 country.

Cesar A SommerSection of Gastroenterology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
Amalia CapillaSection of Gastroenterology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
Francisco J Molina-EstevezSection of Gastroenterology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
Andreia Gianotti-SommerSection of Gastroenterology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
Nicholas SkvirCenter for Regenerative Medicine (CReM), Boston University School of Medicine, Boston, Massachusetts, United States of America.ORCID 0000-0002-3067-4458
Ignacio CaballeroCenter for Regenerative Medicine (CReM), Boston University School of Medicine, Boston, Massachusetts, United States of America.
Sanjib ChowdhurySection of Gastroenterology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
Gustavo MostoslavskySection of Gastroenterology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.ORCID 0000-0002-0784-2169
Boston University · US

Funding

A National iPS Cell Network with Deep Phenotyping for Translational ResearchU01TR001810 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI GILAD, YOAV, KOTTON, DARRELL N. · 2016 to 2020
$4.4M
NRSA Training CoreTL1TR001410 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI KOTTON, DARRELL N. · 2015 to 2024
$4.3M
A National Resource for Lung disease-specific iPS cellsR24HL123828 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI KOTTON, DARRELL N., MOSTOSLAVSKY, GUSTAVO · 2014 to 2018
$2.7M
NCATS NIH HHS TL1 TR001410NCATS NIH HHS U01 TR001810NHLBI NIH HHS R24 HL123828
6 · The paper itself

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.

Indexed as

MutagenesisMutationAdenomatous Polyposis ColiAdenomatous Polyposis Coli ProteinCell DifferentiationCells, CulturedCell Transformation, NeoplasticGene Expression Regulation, DevelopmentalHEK293 CellsHumansInduced Pluripotent Stem CellsIntestinesOrganoidsSignal TransductionAdenomatous Polyposis Coli Protein

Identifiers

PMID30024920
PMCPMC6053155
OpenAlexW2884321202

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.