Evidence map›Paper›PMID 32556182›Full record

ArticleInflammatory bowel diseases2021

Colonoids From Patients With Pediatric Inflammatory Bowel Disease Exhibit Decreased Growth Associated With Inflammation Severity and Durable Upregulation of Antigen Presentation Genes.

Judith R Kelsen, Noor Dawany, Maire A Conrad, Tatiana A Karakasheva, Kelly Maurer, Jane M Wei, Selen Uman, Maiah H Dent, Rithika Behera, Laura M Bryant and 16 more

Open access · greenAbstract read
In one paragraph

Article in Inflammatory bowel diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.1field-weighted citation impact, top 21% 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

12 citing papers in PubMed, 19 citations in OpenAlex.

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  6. Characterization of patient-derived intestinal organoids for modelling fibrosis in Inflammatory Bowel Disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024
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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

26 authors at 8 institutions in 3 countries.

Judith R KelsenDepartment of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Noor DawanyDepartment of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Maire A ConradDepartment of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Tatiana A KarakashevaDepartment of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Kelly MaurerDivision of Allergy Immunology, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Jane M WeiDepartment of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Selen UmanDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States.
Maiah H DentDepartment of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Rithika BeheraDepartment of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Laura M BryantDepartment of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Xianghui MaDepartment of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Leticia MoreiraDepartment of Gastroenterology, Hospital Clinic, Centro de Investigacion Biomedica en Red en Enfermedades Hepaticas y Digestivas (CIBERehd), IDIBAPS, University of Barcelona, Catalonia, Spain.
Priya ChatterjiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States.
Rawan ShraimDepartment of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Audrey MerzDepartment of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Rei MizunoDepartment of Medicine, Gastroenterology Division, University of Pennsylvania, Philadelphia, PA, United States.
Lauren A SimonDepartment of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Amanda B MuirDepartment of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Claudio GiraudoDepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States.
Edward M BehrensDivision of Rheumatology, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Kelly A WhelanFels Institute for Cancer Research & Molecular Biology, Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States.
Marcella DevotoDivision of Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Pierre A RussoDepartment of Pediatrics, Oregon Health & Science University, Portland, OR, United States.
Sarah F AndresDepartment of Translational and Precision Medicine, University of Rome Sapienza, Rome, Italy.
Kathleen E SullivanDivision of Allergy Immunology, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Kathryn E HamiltonDepartment of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Children's Hospital of Philadelphia · USUniversity of Pennsylvania · USCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas · ESHarvard University · USOregon Health & Science University · USSapienza University of Rome · ITTemple University · USThomas Jefferson University · US

Funding

TRANSGENIC AND CHIMERIC MOUSE COREP30DK050306 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI REBECCA G WELLS · 1997 to 2026
$32.5M
Integration of genomics and transcriptomics to investigate biological pathways in very early onset IBDR01DK127044 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI KELSEN, JUDITH RACHEL · 2021 to 2025
$3.4M
Defining post-transcriptional regulons in intestinal epithelial regenerationR01DK124369 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI HAMILTON, KATHRYN ELIZABETH · 2020 to 2024
$2.6M
Investigating the role of mitochondria in Eosinophilic Esophagitis pathogenesis.R01DK121159 · NIDDK · TEMPLE UNIV OF THE COMMONWEALTH · PI WHELAN, KELLY A · 2019 to 2023
$2.4M
Role of Stx11 and STXBP2 in lytic granule exocytosis in health and diseaseR01AI123538 · NIAID · THOMAS JEFFERSON UNIVERSITY · PI GIRAUDO, CLAUDIO GUILLERMO · 2017 to 2021
$2.1M
Very Early-onset inflammatory bowel diseaseK23DK100461 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI KELSEN, JUDITH RACHEL · 2014 to 2018
$893k
Lysyl oxidase mediated fibrosis in eosinophilic esophagitisK08DK106444 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI MUIR, AMANDA BROOKE · 2015 to 2019
$778k
An integrative approach to understanding the genetic basis of very early onset inflammatory bowel diseaseR01DK111843 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI KELSEN, JUDITH RACHEL · 2018 to 2020
$772k
The functional role of mitophagy in esophageal cell biologyK01DK103953 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI WHELAN, KELLY A · 2015 to 2019
$637k
The role of IMP1 mRNA binding protein in intestinal epithelial biologyK01DK100485 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI HAMILTON, KATHRYN ELIZABETH · 2014 to 2018
$631k
The Role of Lysyl Oxidase in Epithelial Differentiation in Eosinophilic EsophagitisR03DK118310 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI MUIR, AMANDA BROOKE · 2019 to 2020
$264k
IMP1 REGULATION OF AUTOPHAGY IN THE INTESTINAL EPITHELIUMR03DK114463 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI HAMILTON, KATHRYN ELIZABETH · 2017 to 2018
$156k
NIAID NIH HHS R01 AI123538NIDDK NIH HHS K01 DK100485NIDDK NIH HHS K01 DK103953NIDDK NIH HHS K08 DK106444NIDDK NIH HHS K23 DK100461NIDDK NIH HHS P30 DK050306NIDDK NIH HHS R01 DK111843NIDDK NIH HHS R01 DK121159NIDDK NIH HHS R01 DK124369NIDDK NIH HHS R01 DK127044NIDDK NIH HHS R03 DK114463NIDDK NIH HHS R03 DK118310
6 · The paper itself

Abstract

backgroundDefining epithelial cell contributions to inflammatory bowel disease (IBD) is essential for the development of much needed therapies for barrier repair. Children with very early onset (VEO)-IBD have more extensive, severe, and refractory disease than older children and adults with IBD and, in some cases, have defective barrier function. We therefore evaluated functional and transcriptomic differences between pediatric IBD (VEO and older onset) and non-IBD epithelium using 3-dimensional, biopsy-derived organoids.

methodsWe measured growth efficiency relative to histopathological and clinical parameters in patient enteroid (ileum) and colonoid (colon) lines. We performed RNA-sequencing on patient colonoids and subsequent flow cytometry after multiple passages to evaluate changes that persisted in culture.

resultsEnteroids and colonoids from pediatric patients with IBD exhibited decreased growth associated with histological inflammation compared with non-IBD controls. We observed increased LYZ expression in colonoids from pediatric IBD patients, which has been reported previously in adult patients with IBD. We also observed upregulation of antigen presentation genes HLA-DRB1 and HLA-DRA, which persisted after prolonged passaging in patients with pediatric IBD.

conclusionsWe present the first functional evaluation of enteroids and colonoids from patients with VEO-IBD and older onset pediatric IBD, a subset of which exhibits poor growth. Enhanced, persistent epithelial antigen presentation gene expression in patient colonoids supports the notion that epithelial cell-intrinsic differences may contribute to IBD pathogenesis.

Indexed as

Antigen PresentationInflammatory Bowel DiseasesChildHumansInflammationOrganoidsUp-Regulationcolonoidsenteroidsepithelial cellsinflammatory bowel diseaseVEO-IBD

Identifiers

PMID32556182
PMCPMC7813751
OpenAlexW3035888534

What OpenQuestion holds

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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.