Evidence map›Paper›PMID 31913277›Full record

ArticleNature communications2020

Prox1-positive cells monitor and sustain the murine intestinal epithelial cholinergic niche.

Moritz Middelhoff, Henrik Nienhüser, Giovanni Valenti, H Carlo Maurer, Yoku Hayakawa, Ryota Takahashi, Woosook Kim, Zhengyu Jiang, Ermanno Malagola, Krystle Cuti and 6 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
3.0field-weighted citation impact, top 7% 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

48 citing papers in PubMed, 60 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Selective modulation of murine intestinal MAmerican journal of physiology. Cell physiology · 2026
    Article
  6. Article
  7. Review
  8. Article
  9. The IL-18 receptor is expressed on murine small-intestinal enterochromaffin cells and executes a recovery program upon injury.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. Article
  11. Article
  12. The supernatant ofFrontiers in microbiology · 2025
    Article
  13. Article
  14. Tuft cells in the intestine, immunity and beyond.Nature reviews. Gastroenterology & hepatology · 2024
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Cholinergic Mechanisms in Gastrointestinal Neoplasia.International journal of molecular sciences · 2024
    Review
  20. 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

16 authors at 4 institutions in 3 countries.

Moritz MiddelhoffDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY, 10032, USA.ORCID http://orcid.org/0000-0001-8425-3985
Henrik NienhüserDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY, 10032, USA.ORCID http://orcid.org/0000-0002-0475-9538
Giovanni ValentiDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY, 10032, USA.
H Carlo MaurerKlinikum rechts der Isar, II. Medizinische Klinik, Technische Universität München, 81675, Munich, Germany.ORCID http://orcid.org/0000-0002-2193-6014
Yoku HayakawaGraduate School of Medicine, Department of Gastroenterology, The University of Tokyo, Tokyo, 113-0033, Japan.
Ryota TakahashiDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY, 10032, USA.ORCID http://orcid.org/0000-0001-7886-8481
Woosook KimDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY, 10032, USA.
Zhengyu JiangDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY, 10032, USA.ORCID http://orcid.org/0000-0002-3235-0326
Ermanno MalagolaDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY, 10032, USA.ORCID http://orcid.org/0000-0001-9294-3097
Krystle CutiDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY, 10032, USA.ORCID http://orcid.org/0000-0001-8137-8782
Yagnesh TailorDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY, 10032, USA.
Leah B ZamechekDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY, 10032, USA.ORCID http://orcid.org/0000-0003-2863-2950
Bernhard W RenzKlinik für Allgemein-, Viszeral- und Transplantationschirurgie, Ludwig-Maximilians-Universität München, 81377, Munich, Germany.ORCID http://orcid.org/0000-0001-9574-8051
Michael QuanteKlinikum rechts der Isar, II. Medizinische Klinik, Technische Universität München, 81675, Munich, Germany.
Kelley S YanDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY, 10032, USA.
Timothy C WangDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY, 10032, USA. tcw21@cumc.columbia.edu.ORCID http://orcid.org/0000-0001-5730-3019
Columbia University Irving Medical Center · USTUM Klinikum · DELudwig-Maximilians-Universität München · DEThe University of Tokyo · JP

Funding

The Role of Stem Cells and the Microenvironment in Gastrointestinal CancersR35CA210088 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Timothy Cragin Wang · 2017 to 2026
$10.2M
Understanding stem cell heterogeneity and niche function in intestinal regeneration after irradiationU01DK103155 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GUHA, CHANDAN, WANG, TIMOTHY CRAGIN · 2014 to 2023
$4.4M
Limited Competition for the Continuation of the Intestinal Stem Cell Consortium Coordinating CenterU24DK085532 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI NILAND, JOYCE CAROL · 2019 to 2023
$2.3M
NCI NIH HHS R35 CA210088NIDDK NIH HHS U01 DK103155NIDDK NIH HHS U24 DK085532
6 · The paper itself

Abstract

The enteric neurotransmitter acetylcholine governs important intestinal epithelial secretory and immune functions through its actions on epithelial muscarinic Gq-coupled receptors such as M3R. Its role in the regulation of intestinal stem cell function and differentiation, however, has not been clarified. Here, we find that nonselective muscarinic receptor antagonism in mice as well as epithelial-specific ablation of M3R induces a selective expansion of DCLK1-positive tuft cells, suggesting a model of feedback inhibition. Cholinergic blockade reduces Lgr5-positive intestinal stem cell tracing and cell number. In contrast, Prox1-positive endocrine cells appear as primary sensors of cholinergic blockade inducing the expansion of tuft cells, which adopt an enteroendocrine phenotype and contribute to increased mucosal levels of acetylcholine. This compensatory mechanism is lost with acute irradiation injury, resulting in a paucity of tuft cells and acetylcholine production. Thus, enteroendocrine tuft cells appear essential to maintain epithelial homeostasis following modifications of the cholinergic intestinal niche.

Indexed as

AcetylcholineAnimalsDoublecortin-Like KinasesEnteroendocrine CellsFemaleHomeodomain ProteinsIntestinal MucosaMaleMiceMice, Inbred C57BLNeurotransmitter AgentsProspero-Related Homeobox 1 ProteinProtein Serine-Threonine KinasesReceptors, G-Protein-CoupledTumor Suppressor ProteinsAcetylcholineDclk1 protein, mouseDoublecortin-Like KinasesHomeodomain ProteinsLgr5 protein, mouseNeurotransmitter AgentsProspero-Related Homeobox 1 ProteinProtein Serine-Threonine KinasesReceptors, G-Protein-CoupledTumor Suppressor Proteins

Identifiers

PMID31913277
PMCPMC6949263
OpenAlexW3000625295

What OpenQuestion holds

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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.