Evidence map›Paper›PMID 25569105›Full record

ArticleCell death & disease2015

A tight control of Rif1 by Oct4 and Smad3 is critical for mouse embryonic stem cell stability.

P Li, X Ma, I R Adams, P Yuan

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

Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

11 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
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  4. Article
  5. Article
  6. Article
  7. Glucose-6-Phosphate Dehydrogenase, Redox Homeostasis and Embryogenesis.International journal of molecular sciences · 2022
    Review
  8. Article
  9. Article
  10. Review
  11. Article
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

4 authors at 2 institutions in 2 countries.

P Li1] Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China [2] Department of Chemical Pathology, Stem Cell and Functional Genomics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China [3] The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, China.
X Ma1] Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China [2] Department of Chemical Pathology, Stem Cell and Functional Genomics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
I R AdamsMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
P Yuan1] Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China [2] Department of Chemical Pathology, Stem Cell and Functional Genomics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China [3] The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, China [4] School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
Chinese University of Hong Kong · CNMRC Institute of Genetics and Molecular Medicine · GB

Funding

Medical Research Council MC_PC_U127580973
6 · The paper itself

Abstract

Prolonged culture of embryonic stem cells (ESCs) leads them to adopt embryonal carcinoma cell features, creating enormous dangers for their further application. The mechanism involved in ESC stability has not, however, been extensively studied. We previously reported that SMAD family member 3 (Smad3) has an important role in maintaining mouse ESC stability, as depletion of Smad3 results in cancer cell-like properties in ESCs and Smad3-/- ESCs are prone to grow large, malignant teratomas. To understand how Smad3 contributes to ESC stability, we performed microarray analysis to compare the transcriptome of wild-type and Smad3-/- ESCs. We found that Rif1 (RAP1-associated protein 1), a factor important for genomic stability, is significantly upregulated in Smad3-/- ESCs. The expression level of Rif1 needs to be tightly controlled in ESCs, as a low level of Rif1 is associated with ESC differentiation, but a high level of Rif1 is linked to ESC transformation. In ESCs, Oct4 activates Rif1, whereas Smad3 represses its expression. Oct4 recruits Smad3 to bind to Rif1 promoter, but Smad3 joining facilitates the loading of a polycomb complex that generates a repressive epigenetic modification on Rif1 promoter, and thus maintains the expression of Rif1 at a proper level in ESCs. Interestingly, Rif1 short hairpin RNA (shRNA)-transduced Smad3-/- ESCs showed less malignant properties than the control shRNA-transduced Smad3-/- ESCs, suggesting a critical role of Rif1 in maintaining the stability of ESCs during proliferation.

Indexed as

AnimalsCell DifferentiationCell MovementCell ProliferationDNA RepairEmbryonic Stem CellsGene Expression ProfilingGene Expression Regulation, DevelopmentalGene Knockdown TechniquesHistonesLysineMethylationMiceModels, BiologicalOctamer Transcription Factor-3Promoter Regions, GeneticHistonesLysineOctamer Transcription Factor-3Pou5f1 protein, mouseRif1 protein, mouseRNA, MessengerRNA, Small InterferingSmad3 ProteinSmad3 protein, mouseTelomere-Binding Proteins

Identifiers

PMID25569105
PMCPMC4669749
OpenAlexW2002737111

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.