Evidence map›Paper›PMID 28346462›Full record

ArticlePLoS genetics2017

Wnt/Tcf1 pathway restricts embryonic stem cell cycle through activation of the Ink4/Arf locus.

Anchel De Jaime-Soguero, Francesco Aulicino, Gokhan Ertaylan, Anna Griego, Aniello Cerrato, Aravind Tallam, Antonio Del Sol, Maria Pia Cosma, Frederic Lluis

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

32 citing papers in PubMed, 71 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Wnt Signaling in the Breast: From Development to Disease.Frontiers in cell and developmental biology · 2022
    Review
  17. G1-phase progression in pluripotent stem cells.Cellular and molecular life sciences : CMLS · 2021
    Review
  18. Review
  19. Article
  20. 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

9 authors at 7 institutions in 6 countries.

Anchel De Jaime-SogueroKU Leuven Stem Cell Institute, Department of Development and Regeneration, Stem Cell Signalling laboratory, Herestraat 49, Onderwijs en Navorsing 4, Leuven, Belgium.
Francesco AulicinoCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, Spain.ORCID 0000-0002-3097-3765
Gokhan ErtaylanMaastricht Centre for Systems Biology (MaCSBio), Maastricht University. Universiteitssingel 60, 6229 ER Maastricht, The Netherlands.ORCID 0000-0001-5602-6435
Anna GriegoKU Leuven Stem Cell Institute, Department of Development and Regeneration, Stem Cell Signalling laboratory, Herestraat 49, Onderwijs en Navorsing 4, Leuven, Belgium.
Aniello CerratoIstituto per l'Endocrinologia e l'Oncologia Sperimentale "Gaetano Salvatore", CNR, Napoli, Italy.
Aravind TallamTWINCORE, Zentrum für Experimentelle und Klinische Infektionsforschung, Hannover, Germany.ORCID 0000-0001-7714-9872
Antonio Del SolLuxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts-Fourneaux, L-4362 Esch-sur-Alzette, Luxembourg.ORCID 0000-0002-9926-617X
Maria Pia CosmaCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, Spain.
Frederic LluisKU Leuven Stem Cell Institute, Department of Development and Regeneration, Stem Cell Signalling laboratory, Herestraat 49, Onderwijs en Navorsing 4, Leuven, Belgium.ORCID 0000-0002-7296-7611
KU Leuven · BECenter for Experimental and Clinical Infection Research · DECentre for Genomic Regulation · ESInstitució Catalana de Recerca i Estudis Avançats · ESInstitute for Experimental Endocrinology and Oncology · ITMaastricht University · NLUniversity of Luxembourg · LU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Understanding the mechanisms regulating cell cycle, proliferation and potency of pluripotent stem cells guarantees their safe use in the clinic. Embryonic stem cells (ESCs) present a fast cell cycle with a short G1 phase. This is due to the lack of expression of cell cycle inhibitors, which ultimately determines naïve pluripotency by holding back differentiation. The canonical Wnt/β-catenin pathway controls mESC pluripotency via the Wnt-effector Tcf3. However, if the activity of the Wnt/β-catenin controls the cell cycle of mESCs remains unknown. Here we show that the Wnt-effector Tcf1 is recruited to and triggers transcription of the Ink4/Arf tumor suppressor locus. Thereby, the activation of the Wnt pathway, a known mitogenic pathway in somatic tissues, restores G1 phase and drastically reduces proliferation of mESCs without perturbing pluripotency. Tcf1, but not Tcf3, is recruited to a palindromic motif enriched in the promoter of cell cycle repressor genes, such as p15Ink4b, p16Ink4a and p19Arf, which mediate the Wnt-dependent anti-proliferative effect in mESCs. Consistently, ablation of β-catenin or Tcf1 expression impairs Wnt-dependent cell cycle regulation. All together, here we showed that Wnt signaling controls mESC pluripotency and proliferation through non-overlapping functions of distinct Tcf factors.

Indexed as

AnimalsBase SequenceBlotting, WesternCell CycleCell ProliferationCells, CulturedCyclin-Dependent Kinase Inhibitor p15Cyclin-Dependent Kinase Inhibitor p16Gene Expression RegulationGene Knockdown TechniquesHEK293 CellsHepatocyte Nuclear Factor 1-alphaHumansMiceMice, TransgenicMouse Embryonic Stem CellsCdkn2a protein, mouseCyclin-Dependent Kinase Inhibitor p15Cyclin-Dependent Kinase Inhibitor p16Hepatocyte Nuclear Factor 1-alphaHnf1a protein, mouse

Identifiers

PMID28346462
PMCPMC5386305
OpenAlexW2599220309

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.