Evidence map›Paper›PMID 31805439›Full record

ArticleCellular and molecular gastroenterology and hepatology2020

DNA Methylation Analysis Validates Organoids as a Viable Model for Studying Human Intestinal Aging.

Sophia K Lewis, Daniel Nachun, Martin G Martin, Steve Horvath, Giovanni Coppola, D Leanne Jones

Open access · goldAbstract read
In one paragraph

Article in Cellular and molecular gastroenterology and hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 5% 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

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.

  1. Pooled it
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  16. Review
  17. Spheroids and organoids derived from colorectal cancer as tools forExploration of targeted anti-tumor therapy · 2024
    Review
  18. Review
  19. Experimental models for ageing research.Histology and histopathology · 2023
    Review
  20. Stem cells for organoids.Smart medicine · 2022
    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 1 institution in 1 country.

Sophia K LewisDepartment of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California; Eli and Edythe Broad Stem Cell Research Center, University of California Los Angeles, Los Angeles, California.
Daniel NachunDepartment of Psychiatry and Semel Institute, University of California Los Angeles, Los Angeles, California.
Martin G MartinEli and Edythe Broad Stem Cell Research Center, University of California Los Angeles, Los Angeles, California; Division of Gastroenterology and Nutrition, Department of Pediatrics, Mattel Children's Hospital and David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
Steve HorvathDepartment of Human Genetics, Gonda Research Center, David Geffen School of Medicine, Los Angeles, California.
Giovanni CoppolaDepartment of Psychiatry and Semel Institute, University of California Los Angeles, Los Angeles, California; Department of Neurology, University of California Los Angeles, Los Angeles, California.
D Leanne JonesDepartment of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California; Eli and Edythe Broad Stem Cell Research Center, University of California Los Angeles, Los Angeles, California. Electronic address: leannejones@ucla.edu.
University of California, Los Angeles · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
Intestinal Stem Cell Culture and Entero-Endocrine Lineage DevelopmentU01DK085535 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUNN, JAMES C, MARTIN, MARTIN G · 2009 to 2018
$3.7M
Validation and optimization of epigenetic clocksU01AG060908 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RITZ, BEATE R. · 2018 to 2022
$3.4M
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 P30 CA016042NIA NIH HHS U01 AG060908NIDDK NIH HHS P30 DK041301NIDDK NIH HHS U01 DK085535NIDDK NIH HHS U24 DK085532
6 · The paper itself

Abstract

BACKGROUND &

aimsThe epithelia of the intestine and colon turn over rapidly and are maintained by adult stem cells at the base of crypts. Although the small intestine and colon have distinct, well-characterized physiological functions, it remains unclear if there are fundamental regional differences in stem cell behavior or region-dependent degenerative changes during aging. Mesenchyme-free organoids provide useful tools for investigating intestinal stem cell biology in vitro and have started to be used for investigating age-related changes in stem cell function. However, it is unknown whether organoids maintain hallmarks of age in the absence of an aging niche. We tested whether stem cell-enriched organoids preserved the DNA methylation-based aging profiles associated with the tissues and crypts from which they were derived.

methodsTo address this, we used standard human methylation arrays and the human epigenetic clock as a biomarker of age to analyze in vitro-derived, 3-dimensional, stem cell-enriched intestinal organoids.

resultsWe found that human stem cell-enriched organoids maintained segmental differences in methylation patterns and that age, as measured by the epigenetic clock, also was maintained in vitro. Surprisingly, we found that stem cell-enriched organoids derived from the small intestine showed striking epigenetic age reduction relative to organoids derived from colon.

conclusionsOur data validate the use of organoids as a model for studying human intestinal aging and introduce methods that can be used when modeling aging or age-onset diseases in vitro.

Indexed as

AdolescentAdultAdult Stem CellsAgedAged, 80 and overAgingCells, CulturedChild, PreschoolColonDNA MethylationEpigenesis, GeneticHumansInfantInfant, NewbornIntestinal MucosaIntestine, SmallAgingDNA MethylationEpigenetic ClockIntestinal Stem CellsOrganoids

Identifiers

PMID31805439
PMCPMC7044532
OpenAlexW2991775683

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.