Evidence map›Paper›PMID 40467544›Full record

ArticleNature communications2025

Epithelial GREMLIN1 disrupts intestinal epithelial-mesenchymal crosstalk to induce a wnt-dependent ectopic stem cell niche through stromal remodelling.

Eoghan J Mulholland, Hayley L Belnoue-Davis, Gabriel N Valbuena, Nuray Gunduz, Amelia Ligeza, Muyang Lin, Sujata Biswas, Ester Gil Vasquez, Sulochana Omwenga, Nadia Nasreddin and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. 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

24 authors.

Eoghan J Mulholland *Centre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-1200-9825
Hayley L Belnoue-Davis *Centre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK. hayley.davis@well.ox.ac.uk.ORCID http://orcid.org/0000-0003-2914-4932
Gabriel N ValbuenaCentre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK.
Nuray GunduzCancer Research UK Scotland Centre, Glasgow, UK.
Amelia LigezaCentre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK.
Muyang LinCentre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK.
Sujata BiswasCentre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK.
Ester Gil VasquezCentre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK.
Sulochana OmwengaCentre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK.
Nadia NasreddinCentre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK.
Michael C HodderCancer Research UK Scotland Centre, Glasgow, UK.
Lai Mun WangDepartment of Laboratory Medicine, Changi General Hospital, Singapore, Singapore.
Aik Seng NgDepartment of Oncology, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-1925-4759
Elizabeth JenningsKennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science University of Oxford, Oxford, UK.
Kim S MidwoodKennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-8813-2977
Neesha DediUK Research, UCB Pharma, Slough, Berkshire, UK.ORCID http://orcid.org/0009-0000-7516-5449
Shazia IrshadCentre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-4536-373X
Rachel A RidgwayCancer Research UK Scotland Centre, Glasgow, UK.ORCID http://orcid.org/0000-0003-0198-8244
Toby J PhesseDepartment of Oncology, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-9568-4916
James EastTranslational Gastroenterology Unit, John Radcliffe Hospital, University of Oxford, and Oxford NIHR Biomedical Research Centre, Oxford, UK.ORCID http://orcid.org/0000-0001-8035-3700
Ian Pm TomlinsonDepartment of Oncology, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-3037-1470
Gareth Cg DaviesUK Research, UCB Pharma, Slough, Berkshire, UK.ORCID http://orcid.org/0000-0001-5180-3143
Owen J SansomCancer Research UK Scotland Centre, Glasgow, UK.ORCID http://orcid.org/0000-0001-9540-3010
Simon J LeedhamCentre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-1476-6982

Funding

Cancer Research UK (CRUK) A26825 and A28223Cancer Research UK (CRUK) DRCNPG-Jun22\100002University of Oxford (Oxford University) Lee Placito FellowshipWellcome TrustWellcome Trust (Wellcome) 090532/Z/09/ZWellcome Trust (Wellcome) 206314/Z/17/Z
6 · The paper itself

Abstract

In homeostasis, counterbalanced morphogen signalling gradients along the vertical axis of the intestinal mucosa regulate the fate and function of epithelial and stromal cell compartments. Here, we use a disease-positioned mouse and human tissue to explore the consequences of pathological BMP signalling dysregulation on epithelial-mesenchymal interaction. Aberrant pan-epithelial expression of the secreted BMP antagonist Grem1 results in ectopic crypt formation, with lineage tracing demonstrating the presence of Lgr5(-) stem/progenitor cells. Isolated epithelial cell Grem1 expression has no effect on individual cell fate, indicating an intercompartmental impact of mucosal-wide BMP antagonism. Treatment with an anti-Grem1 antibody abrogates the polyposis phenotype, and triangulation of specific pathway inhibitors defines a pathological sequence of events, with Wnt-ligand-dependent ectopic stem cell niches forming through stromal remodelling following BMP disruption. These data support an emerging co-evolutionary model of intestinal cell compartmentalisation based on bidirectional regulation of epithelial-mesenchymal cell fate and function.

Indexed as

Intercellular Signaling Peptides and ProteinsIntestinal MucosaStem Cell NicheAnimalsBone Morphogenetic ProteinsCytokinesEpithelial CellsEpithelial-Mesenchymal TransitionHumansMiceMice, Inbred C57BLReceptors, G-Protein-CoupledStem CellsStromal CellsWnt ProteinsWnt Signaling PathwayBone Morphogenetic ProteinsCytokinesGREM1 protein, humanGrem1 protein, mouseIntercellular Signaling Peptides and ProteinsLgr5 protein, mouseReceptors, G-Protein-CoupledWnt Proteins

Identifiers

PMID40467544
PMCPMC12137559

What Socratic 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 Socratic graph.