Evidence map›Paper›PMID 33174295›Full record

ArticleNeurogastroenterology and motility2021

Intrinsic cholinergic innervation in the human sigmoid colon revealed using CLARITY, three-dimensional (3D) imaging, and a novel anti-human peripheral choline acetyltransferase (hpChAT) antiserum.

Pu-Qing Yuan, Jean-Pierre Bellier, Tao Li, Mary R Kwaan, Hiroshi Kimura, Yvette Taché

Open access · greenAbstract read
In one paragraph

Article in Neurogastroenterology and motility, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.0field-weighted citation impact, top 27% 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, 17 citations in OpenAlex.

  1. Article
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  4. Imaging the enteric nervous system.Frontiers in neuroanatomy · 2025
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  8. The enteric nervous system.Physiological reviews · 2023
    Review
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  13. Article
  14. Classification of human enteric neurons.Histochemistry and cell biology · 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

6 authors at 3 institutions in 2 countries.

Pu-Qing YuanUCLA/Digestive Diseases Research Core Center, Vatche and Tamar Manoukian Digestive Diseases Division, Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA, USA.ORCID 0000-0002-0067-510X
Jean-Pierre BellierMolecular Neuroscience Research Center, Shiga University of Medical Science, Otsu, Japan.
Tao LiUCLA/Digestive Diseases Research Core Center, Vatche and Tamar Manoukian Digestive Diseases Division, Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA, USA.
Mary R KwaanDepartment of Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, USA.
Hiroshi KimuraMolecular Neuroscience Research Center, Shiga University of Medical Science, Otsu, Japan.
Yvette TachéUCLA/Digestive Diseases Research Core Center, Vatche and Tamar Manoukian Digestive Diseases Division, Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA, USA.
Center for Digestive and Liver Diseases · USShiga University of Medical Science · JPUniversity of California, Los Angeles · US

Funding

Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
Comprehensive Structural and Functional Mapping of Mammalian Colonic Nervous SystemOT2OD024899 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MULUGETA, MILLION, TACHE, YVETTE FRANCE · 2017 to 2021
$13.1M
NIDDK NIH HHS P30 DK041301NIH HHS OT2 OD024899
6 · The paper itself

Abstract

backgroundWe previously reported the specificity of a novel anti-human peripheral choline acetyltransferase (hpChAT) antiserum for immunostaining of cholinergic neuronal cell bodies and fibers in the human colon. In this study, we investigate 3D architecture of intrinsic cholinergic innervation in the human sigmoid colon and the relationship with nitrergic neurons in the enteric plexus.

methodsWe developed a modified CLARITY tissue technique applicable for clearing human sigmoid colon specimens and immunostaining with hpChAT antiserum and co-labeling with neuronal nitric oxide synthase (nNOS) antibody. The Z-stack confocal images were processed for 3D reconstruction/segmentation/digital tracing and computational quantitation by Imaris 9.2 and 9.5. KEY

resultsIn the mucosa, a local micro-neuronal network formed of hpChAT-ir fibers and a few neuronal cell bodies were digitally assembled. Three layers of submucosal plexuses were displayed in 3D structure that were interconnected by hpChAT-ir fiber bundles and hpChAT-ir neurons were rarely co-labeled by nNOS. In the myenteric plexus, 30.1% of hpChAT-ir somas including Dogiel type I and II were co-labeled by nNOS and 3 classes of hpChAT-ir nerve fiber strands were visualized in 3D images and videos. The density and intensity values of hpChAT-ir fibers in 3D structure were significantly higher in the circular than in the longitudinal layer. CONCLUSIONS AND INFERENCES: The intrinsic cholinergic innervation in the human sigmoid colon was demonstrated layer by layer for the first time in 3D microstructures. This may open a new venue to assess the structure-function relationships and pathological alterations in colonic diseases.

Indexed as

AdultCholine O-AcetyltransferaseCholinergic NeuronsColon, SigmoidEnteric Nervous SystemFemaleHumansImaging, Three-DimensionalImmunohistochemistryMaleMiddle AgedCholine O-Acetyltransferase3D imagingcholinergic innervationenteric nervous systemhuman sigmoid colonnitric oxide synthase

Identifiers

PMID33174295
PMCPMC8126258
OpenAlexW3105814048

What OpenQuestion holds

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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.