Evidence map›Paper›PMID 29374777›Full record

ArticleJournal of gastroenterology2018

Single cell analysis of Crohn's disease patient-derived small intestinal organoids reveals disease activity-dependent modification of stem cell properties.

Kohei Suzuki, Tatsuro Murano, Hiromichi Shimizu, Go Ito, Toru Nakata, Satoru Fujii, Fumiaki Ishibashi, Ami Kawamoto, Sho Anzai, Reiko Kuno and 12 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of gastroenterology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 4% 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

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.

  1. Pooled it
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  7. Apical-out bovine intestinal organoids as an infection model forCurrent research in parasitology & vector-borne diseases · 2025
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  12. Recent Advances in Cell-Based In Vitro Models to Recreate Human Intestinal Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Review
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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

22 authors at 1 institution in 1 country.

Kohei SuzukiDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Tatsuro MuranoDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Hiromichi ShimizuDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Go ItoDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Toru NakataDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Satoru FujiiDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Fumiaki IshibashiDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Ami KawamotoDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Sho AnzaiDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Reiko KunoDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Konomi KuwabaraDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Junichi TakahashiDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Minami HamaDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Sayaka NagataDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Yui HiraguriDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Kento TakenakaDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Shiro YuiCenter for Stem Cell and Regenerative Medicine, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
Kiichiro TsuchiyaDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Tetsuya NakamuraDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Kazuo OhtsukaDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Mamoru WatanabeDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Ryuichi OkamotoDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan. rokamoto.gast@tmd.ac.jp.ORCID http://orcid.org/0000-0002-7047-571X
Tokyo Medical and Dental University · JP

Funding

Japan Agency for Medical Research and Development 16bm0304001h0004Japan Agency for Medical Research and Development 17ek0109188h0002Japan Society for the Promotion of Science 16H05284Japan Society for the Promotion of Science 26221307
6 · The paper itself

Abstract

backgroundIntestinal stem cells (ISCs) play indispensable roles in the maintenance of homeostasis, and also in the regeneration of the damaged intestinal epithelia. However, whether the inflammatory environment of Crohn's disease (CD) affects properties of resident small intestinal stem cells remain uncertain.

methodsCD patient-derived small intestinal organoids were established from enteroscopic biopsy specimens taken from active lesions (aCD-SIO), or from mucosa under remission (rCD-SIO). Expression of ISC-marker genes in those organoids was examined by immunohistochemistry, and also by microfluid-based single-cell multiplex gene expression analysis. The ISC-specific function of organoid cells was evaluated using a single-cell organoid reformation assay.

resultsISC-marker genes, OLFM4 and SLC12A2, were expressed by an increased number of small intestinal epithelial cells in the active lesion of CD. aCD-SIOs, rCD-SIOs or those of non-IBD controls (NI-SIOs) were successfully established from 9 patients. Immunohistochemistry showed a comparable level of OLFM4 and SLC12A2 expression in all organoids. Single-cell gene expression data of 12 ISC-markers were acquired from a total of 1215 cells. t-distributed stochastic neighbor embedding analysis identified clusters of candidate ISCs, and also revealed a distinct expression pattern of SMOC2 and LGR5 in ISC-cluster classified cells derived from aCD-SIOs. Single-cell organoid reformation assays showed significantly higher reformation efficiency by the cells of the aCD-SIOs compared with that of cells from NI-SIOs.

conclusionsaCD-SIOs harbor ISCs with modified marker expression profiles, and also with high organoid reformation ability. Results suggest modification of small intestinal stem cell properties by unidentified factors in the inflammatory environment of CD.

Indexed as

Balloon EnteroscopyBiomarkersBiopsyCalcium-Binding ProteinsCrohn DiseaseDisease ProgressionEpithelial CellsGene ExpressionGranulocyte Colony-Stimulating FactorHumansInflammationIntestine, SmallOrganoidsReceptors, G-Protein-CoupledSingle-Cell AnalysisSolute Carrier Family 12, Member 2BiomarkersCalcium-Binding ProteinsGranulocyte Colony-Stimulating FactorLGR5 protein, humanOLFM4 protein, humanReceptors, G-Protein-CoupledSLC12A2 protein, humanSMOC2 protein, humanSolute Carrier Family 12, Member 2Crohn’s diseaseIntestinal organoidsIntestinal stem cellSingle cell analysis

Identifiers

PMID29374777
PMCPMC6132922
OpenAlexW2792641862

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.