Evidence map›Paper›PMID 24637118›Full record

ArticleGenes & development2014

DNA methylation is required for the control of stem cell differentiation in the small intestine.

Karyn L Sheaffer, Rinho Kim, Reina Aoki, Ellen N Elliott, Jonathan Schug, Lukas Burger, Dirk Schübeler, Klaus H Kaestner

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

110 citing papers in PubMed, 1 synthesis or guideline pooled it, 217 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. HAT1 Regulates Intestinal Stem Cell Proliferation and Differentiation.bioRxiv : the preprint server for biology · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Chromatin remodeling in tissue stem cell fate determination.Cell regeneration (London, England) · 2024
    Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

50 more citing papers are in PubMed but not listed here.

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 3 institutions in 2 countries.

Karyn L SheafferDepartment of Genetics, Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
Rinho Kim
Reina Aoki
Ellen N Elliott
Jonathan Schug
Lukas Burger
Dirk Schübeler
Klaus H Kaestner
University of Pennsylvania · USFriedrich Miescher Institute · CHSIB Swiss Institute of Bioinformatics · CH

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SHELLEY L BERGER · 1985 to 2026
$222.3M
VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL A. LAZAR · 1986 to 2026
$48.3M
TRANSGENIC AND CHIMERIC MOUSE COREP30DK050306 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Ken Hashigiwa Cadwell · 1997 to 2026
$32.5M
Regulatory cascades in gastrointestinal proliferationR37DK053839 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KAESTNER, KLAUS H · 2012 to 2021
$3.8M
NCI NIH HHS P30 CA016520NICHD NIH HHS T32 HD751613NIDDK NIH HHS P30 DK019525NIDDK NIH HHS P30 DK050306NIDDK NIH HHS R37 DK053839NIDDK NIH HHS R37-DK053839
6 · The paper itself

Abstract

The mammalian intestinal epithelium has a unique organization in which crypts harboring stem cells produce progenitors and finally clonal populations of differentiated cells. Remarkably, the epithelium is replaced every 3-5 d throughout adult life. Disrupted maintenance of the intricate balance of proliferation and differentiation leads to loss of epithelial integrity or barrier function or to cancer. There is a tight correlation between the epigenetic status of genes and expression changes during differentiation; however, the mechanism of how changes in DNA methylation direct gene expression and the progression from stem cells to their differentiated descendants is unclear. Using conditional gene ablation of the maintenance methyltransferase Dnmt1, we demonstrate that reducing DNA methylation causes intestinal crypt expansion in vivo. Determination of the base-resolution DNA methylome in intestinal stem cells and their differentiated descendants shows that DNA methylation is dynamic at enhancers, which are often associated with genes important for both stem cell maintenance and differentiation. We establish that the loss of DNA methylation at intestinal stem cell gene enhancers causes inappropriate gene expression and delayed differentiation.

Indexed as

Cell DifferentiationDNA MethylationAnimalsDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesGene DeletionGene Expression Regulation, DevelopmentalIntestine, SmallMiceStem CellsDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDnmt1 protein, mouseDNA methylationDnmt1intestinal stem cell

Identifiers

PMID24637118
PMCPMC3967052
OpenAlexW2151591434

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.