Evidence map›Paper›PMID 34244422›Full record

ArticleLife science alliance2021

Muscarinic receptor M3 contributes to intestinal stem cell maintenance via EphB/ephrin-B signaling.

Toshio Takahashi, Akira Shiraishi, Jun Murata, Shin Matsubara, Satsuki Nakaoka, Shinji Kirimoto, Masatake Osawa

Open access · goldAbstract read
In one paragraph

Article in Life science alliance, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 20% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Goblet cells dictate viral tropism and pathogenesis in nasal and intestinal mucosae.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Article
  5. Article
  6. Review
  7. The Role of Muscarinic Acetylcholine Receptor MInternational journal of molecular sciences · 2024
    Review
  8. Article
  9. Article
  10. Review
  11. Tuft cell-derived acetylcholine regulates epithelial fluid secretion.bioRxiv : the preprint server for biology · 2023
    Article
  12. Prenatal stress induces changes in PAR2- and M3-dependent regulation of colon primitive cells.American journal of physiology. Gastrointestinal and liver physiology · 2022
    Article
  13. Article
  14. Modeling Intestinal Stem Cell Function with Organoids.International journal of molecular sciences · 2021
    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

7 authors at 2 institutions in 1 country.

Toshio TakahashiSuntory Foundation for Life Sciences, Bioorganic Research Institute, Kyoto, Japan takahashi@sunbor.or.jp.ORCID 0000-0002-1822-0939
Akira ShiraishiSuntory Foundation for Life Sciences, Bioorganic Research Institute, Kyoto, Japan.
Jun MurataSuntory Foundation for Life Sciences, Bioorganic Research Institute, Kyoto, Japan.ORCID 0000-0001-7867-330X
Shin MatsubaraSuntory Foundation for Life Sciences, Bioorganic Research Institute, Kyoto, Japan.ORCID 0000-0002-7794-534X
Satsuki NakaokaKAC Co., Ltd. Kyoto, Japan.ORCID 0000-0002-0565-1633
Shinji KirimotoKAC Co., Ltd. Kyoto, Japan.ORCID 0000-0002-9248-9442
Masatake OsawaDepartment of Regenerative Medicine and Applied Biomedical Sciences, Graduate School of Medicine, Gifu University, Gifu, Japan.
Suntory Foundation for Life Sciences · JPGifu University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acetylcholine (ACh) signaling through activation of nicotinic and muscarinic ACh receptors regulates expression of specific genes that mediate and sustain proliferation, differentiation, and homeostasis in the intestinal crypts. This signaling plays a pivotal role in the regulation of intestinal stem cell function, but the details have not been clarified. Here, we performed experiments using type 3 muscarinic acetylcholine receptor (M3) knockout mice and their intestinal organoids and report that endogenous ACh affects the size of the intestinal stem niche via M3 signaling. RNA sequencing of crypts identified up-regulation of the EphB/ephrin-B signaling pathway. Furthermore, using an MEK inhibitor (U0126), we found that mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling, which is downstream of EphB/ephrin-B signaling, is activated in M3-deficient crypts. Collectively, M3, EphB/ephrin-B, and the MAPK/ERK signaling cascade work together to maintain the homeostasis of intestinal epithelial cell growth and differentiation following modifications of the cholinergic intestinal niche.

Indexed as

Signal TransductionAnimalsBiomarkersCell DifferentiationCell ProliferationCell Self RenewalFemaleFluorescent Antibody TechniqueGene ExpressionImmunohistochemistryIntestinal MucosaIntestinesMaleMAP Kinase Signaling SystemMiceMice, KnockoutBiomarkersReceptor, Muscarinic M3Receptors, Eph Family

Identifiers

PMID34244422
PMCPMC8321669
OpenAlexW3182784988

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.