Evidence map›Paper›PMID 33649334›Full record

ArticleNature communications2021

Differential regulation of β-catenin-mediated transcription via N- and C-terminal co-factors governs identity of murine intestinal epithelial stem cells.

Costanza Borrelli, Tomas Valenta, Kristina Handler, Karelia Vélez, Alessandra Gurtner, Giulia Moro, Atefeh Lafzi, Laura de Vargas Roditi, George Hausmann, Isabelle C Arnold and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.3field-weighted citation impact, top 18% 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

12 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Butyrate, IL-4, and EP4 Receptors: A Triad of Colorectal Homeostasis, Protecting Against Onset of Cancer and IBD?BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  5. Article
  6. Article
  7. Intestinal stem cell niche: An upcoming area of immense importance in gastrointestinal disorders.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2025
    Review
  8. The origin and evolution of Wnt signalling.Nature reviews. Genetics · 2024
    Review
  9. Article
  10. Article
  11. Article
  12. 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

12 authors at 2 institutions in 2 countries.

Costanza Borrelli *Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Tomas Valenta *Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland. tomas.valenta@mls.uzh.ch.ORCID 0000-0002-3043-1835
Kristina HandlerDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
Karelia VélezDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
Alessandra GurtnerInstitute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
Giulia MoroDepartment of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-0642-6294
Atefeh LafziDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
Laura de Vargas RoditiDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
George HausmannDepartment of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-2146-6665
Isabelle C ArnoldInstitute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
Andreas E MoorDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.ORCID 0000-0001-8715-8449
Konrad BaslerDepartment of Molecular Life Sciences, University of Zurich, Zurich, Switzerland. konrad.basler@mls.uzh.ch.ORCID 0000-0003-3534-1529
University of Zurich · CHETH Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The homeostasis of the gut epithelium relies upon continuous renewal and proliferation of crypt-resident intestinal epithelial stem cells (IESCs). Wnt/β-catenin signaling is required for IESC maintenance, however, it remains unclear how this pathway selectively governs the identity and proliferative decisions of IESCs. Here, we took advantage of knock-in mice harboring transgenic β-catenin alleles with mutations that specifically impair the recruitment of N- or C-terminal transcriptional co-factors. We show that C-terminally-recruited transcriptional co-factors of β-catenin act as all-or-nothing regulators of Wnt-target gene expression. Blocking their interactions with β-catenin rapidly induces loss of IESCs and intestinal homeostasis. Conversely, N-terminally recruited co-factors fine-tune β-catenin's transcriptional output to ensure proper self-renewal and proliferative behaviour of IESCs. Impairment of N-terminal interactions triggers transient hyperproliferation of IESCs, eventually resulting in exhaustion of the self-renewing stem cell pool. IESC mis-differentiation, accompanied by unfolded protein response stress and immune infiltration, results in a process resembling aberrant "villisation" of intestinal crypts. Our data suggest that IESC-specific Wnt/β-catenin output requires selective modulation of gene expression by transcriptional co-factors.

Indexed as

Transcription, GeneticAlgorithmsAnimalsBase Sequencebeta CateninCell DifferentiationCell ProliferationChromatinChromatin Assembly and DisassemblyHomeostasisHyperplasiaIntestinal MucosaJNK Mitogen-Activated Protein KinasesMiceMutant ProteinsMutationbeta CateninChromatinJNK Mitogen-Activated Protein KinasesMutant ProteinsRNA, MessengerTranscription Factors

Identifiers

PMID33649334
PMCPMC7921392
OpenAlexW3135344934

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.