Evidence map›Paper›PMID 29930978›Full record

ArticleCellular and molecular gastroenterology and hepatology2018

Human Fetal-Derived Enterospheres Provide Insights on Intestinal Development and a Novel Model to Study Necrotizing Enterocolitis (NEC).

Stefania Senger, Laura Ingano, Rachel Freire, Antony Anselmo, Weishu Zhu, Ruslan Sadreyev, William Allan Walker, Alessio Fasano

Open access · goldAbstract read
In one paragraph

Article in Cellular and molecular gastroenterology and hepatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
5.6field-weighted citation impact, top 3% 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

57 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.

  1. Pooled it
  2. Temperature and developmental stage govern intestinal susceptibility to human coronavirus 229E.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  6. Effects of specialized proresolving mediators on gut epithelial barrier in early life.The Journal of pharmacology and experimental therapeutics · 2026
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  11. Development of aApplied and environmental microbiology · 2024
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  15. 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

8 authors at 2 institutions in 1 country.

Stefania SengerDepartment of Pediatrics, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, Massachusetts.
Laura InganoDepartment of Pediatrics, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, Massachusetts.
Rachel FreireDepartment of Pediatrics, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, Massachusetts.
Antony AnselmoDepartment of Molecular Biology, Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Weishu ZhuDepartment of Pediatrics, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, Massachusetts.
Ruslan SadreyevDepartment of Molecular Biology, Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts.
William Allan WalkerDepartment of Pediatrics, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, Massachusetts.
Alessio FasanoDepartment of Pediatrics, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, Massachusetts.
Massachusetts General Hospital · USHarvard University · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
ROLE OF DIETARY CONSTITUENTS ON GENE EXPRESSION IN INTESTINAL EPITHELIUMP30DK040561 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI CHRISTOPHER P DUGGAN · 1994 to 2026
$31.6M
Wild-type S. typhi Infection in Humans: Integrated Immunoprotective MechanismsU19AI082655 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI WHITE, OWEN R · 2009 to 2018
$27.8M
Xenograft and Isograft CoreP01DK033506 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MCCORMICK, BETH A · 1986 to 2015
$24.2M
Microbiome-derived Metabolites Linked to Celiac Disease Onset in Infants at RiskR01DK104344 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI FASANO, ALESSIO · 2016 to 2020
$3.4M
NIAID NIH HHS U19 AI082655NIDDK NIH HHS P01 DK033506NIDDK NIH HHS P30 DK040561NIDDK NIH HHS P30 DK043351NIDDK NIH HHS R01 DK104344
6 · The paper itself

Abstract

BACKGROUND &

aimsUntreated necrotizing enterocolitis (NEC) can lead to massive inflammation resulting in intestinal necrosis with a high mortality rate in preterm infants. Limited access to human samples and relevant experimental models have hampered progress in NEC pathogenesis. Earlier evidence has suggested that bacterial colonization of an immature and developing intestine can lead to an abnormally high inflammatory response to bacterial bioproducts. The aim of our study was to use human fetal organoids to gain insights into NEC pathogenesis.

methodsRNA sequencing analysis was performed to compare patterns of gene expression in human fetal-derived enterospheres (FEnS) and adult-derived enterospheres (AEnS). Differentially expressed genes were analyzed using computational techniques for dimensional reduction, clustering, and gene set enrichment. Unsupervised cluster analysis, Gene Ontology, and gene pathway analysis were used to predict differences between gene expression of samples. Cell monolayers derived from FEnS and AEnS were evaluated for epithelium function and responsiveness to lipopolysaccharide and commensal bacteria.

resultsBased on gene expression patterns, FEnS clustered according to their developmental age in 2 distinct groups: early and late FEnS, with the latter more closely resembling AEnS. Genes involved in maturation, gut barrier function, and innate immunity were responsible for these differences. FEnS-derived monolayers exposed to either lipopolysaccharide or commensal

conclusionsOur results provide insights into processes underlying human intestinal development and support the use of FEnS as a relevant human preclinical model for NEC. Accession number of repository for expression data: GSE101531.

Indexed as

AD, adult duodenalAEnS, adult-derived enterospheresCLDN, claudinCXCL, chemokine (C-X-C motif) ligandDMEM, Dulbecco's modified Eagle mediumEGF, epidermal growth factorEnteroidsFDR, false discovery rateFEnS, fetal-derived enterospheresFetal OrganoidsFITC, fluorescein isothiocyanateHIO, human intestinal organoidHS, Escherichia coli human commensal isolateIFN, interferonIL, interleukinLPS, lipopolysaccharide AMAMP, microbe-associated molecular patternNEC, necrotizing enterocolitisNecrotizing EnterocolitisNF-κB, nuclear factor-κBPBS, phosphate-buffered salinePCR, polymerase chain reactionPGE2, prostaglandin E2RPKM, reads per kilobase of transcript per millionRT-PCR, reverse-transcription polymerase chain reactionTEER, transepithelial electrical resistanceTLR, Toll-like receptorTNF, tumor necrosis factorWAE, wound-associated epithelial cellsΔΔCT, relative threshold cycle

Identifiers

PMID29930978
PMCPMC6009798
OpenAlexW2803752338

What OpenQuestion holds

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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.