Evidence map›Paper›PMID 23831735›Full record

ArticleGut2014

Canonical Wnt signals combined with suppressed TGFβ/BMP pathways promote renewal of the native human colonic epithelium.

Amy Reynolds, Natalia Wharton, Alyson Parris, Esther Mitchell, Anastasia Sobolewski, Christy Kam, Loren Bigwood, Ahmed El Hadi, Andrea Münsterberg, Michael Lewis and 11 more

Open access · hybridAbstract read
In one paragraph

Article in Gut, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

64 citing papers in PubMed, 109 citations in OpenAlex.

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  19. NADNature communications · 2024
    Article
  20. The epithelium takes the stage in asthma and inflammatory bowel diseases.Frontiers in cell and developmental biology · 2024
    Review

4 more citing papers are in PubMed but not listed here.

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

21 authors at 6 institutions in 2 countries.

Amy ReynoldsSchool of Biological Sciences, University of East Anglia, Norwich Research Park, , Norwich, Norfolk, UK.
Natalia Wharton
Alyson Parris
Esther Mitchell
Anastasia Sobolewski
Christy Kam
Loren Bigwood
Ahmed El Hadi
Andrea Münsterberg
Michael Lewis
Christopher Speakman
William Stebbings
Richard Wharton
Kevin Sargen
Richard Tighe
Crawford Jamieson
James Hernon
Sandeep Kapur
Naohide Oue
Wataru Yasui
Mark R Williams
University of East Anglia · GBNorfolk and Norwich University Hospitals NHS Foundation Trust · GBNorwich Research Park · GBNorfolk and Norwich University Hospital · GBHiroshima University · JPQuadram Institute · GB

Funding

Biotechnology and Biological Sciences Research Council BB/D018196/1Biotechnology and Biological Sciences Research Council BB/F015690/1
6 · The paper itself

Abstract

backgroundA defining characteristic of the human intestinal epithelium is that it is the most rapidly renewing tissue in the body. However, the processes underlying tissue renewal and the mechanisms that govern their coordination have proved difficult to study in the human gut.

objectiveTo investigate the regulation of stem cell-driven tissue renewal by canonical Wnt and TGFβ/bone morphogenetic protein (BMP) pathways in the native human colonic epithelium.

designIntact human colonic crypts were isolated from mucosal tissue samples and placed into 3D culture conditions optimised for steady-state tissue renewal. High affinity mRNA in situ hybridisation and immunohistochemistry were complemented by functional genomic and bioimaging techniques. The effects of signalling pathway modulators on the status of intestinal stem cell biology, crypt cell proliferation, migration, differentiation and shedding were determined.

resultsNative human colonic crypts exhibited distinct activation profiles for canonical Wnt, TGFβ and BMP pathways. A population of intestinal LGR5/OLFM4-positive stem/progenitor cells were interspersed between goblet-like cells within the crypt-base. Exogenous and crypt cell-autonomous canonical Wnt signals supported homeostatic intestinal stem/progenitor cell proliferation and were antagonised by TGFβ or BMP pathway activation. Reduced Wnt stimulation impeded crypt cell proliferation, but crypt cell migration and shedding from the crypt surface were unaffected and resulted in diminished crypts.

conclusionsSteady-state tissue renewal in the native human colonic epithelium is dependent on canonical Wnt signals combined with suppressed TGFβ/BMP pathways. Stem/progenitor cell proliferation is uncoupled from crypt cell migration and shedding, and is required to constantly replenish the crypt cell population.

Indexed as

AdultAgedAged, 80 and overBone Morphogenetic ProteinsCell DifferentiationCell MovementCell ProliferationColonHumansIn Situ HybridizationIntestinal MucosaMicroscopy, ConfocalMiddle AgedRegenerationSignal TransductionStem CellsBone Morphogenetic ProteinsTransforming Growth Factor betaEpithelial DifferentiationEpithelial KineticsEpithelial ProliferationImagingStem Cells

Identifiers

PMID23831735
PMCPMC3963552
OpenAlexW2098201429

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.