Evidence map›Paper›PMID 24038750›Full record

ArticleStem cells (Dayton, Ohio)2014

Oct4 maintains the pluripotency of human embryonic stem cells by inactivating p53 through Sirt1-mediated deacetylation.

Zhen-Ning Zhang, Sun-Ku Chung, Zheng Xu, Yang Xu

Open access · greenAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 6% 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

73 citing papers in PubMed, 1 synthesis or guideline pooled it, 135 citations in OpenAlex.

  1. Pooled it
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  14. International journal of biological sciences · 2023
    Article
  15. The SIRT1-c-Myc axis in regulation of stem cells.Frontiers in cell and developmental biology · 2023
    Review
  16. Review
  17. Article
  18. Review
  19. Review
  20. SIRT1 activity orchestrates ECM expression during hESC-chondrogenic differentiation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article

13 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

4 authors at 1 institution in 1 country.

Zhen-Ning ZhangSection of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, California, USA.
Sun-Ku Chung
Zheng Xu
Yang Xu
University of California, San Diego · US

Funding

Genetic Analysis of p53 Stability and ActivityR01CA094254 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI XU, YANG · 2003 to 2012
$2.9M
NCI NIH HHS CA094254NCI NIH HHS R01 CA094254
6 · The paper itself

Abstract

Oct4 is critical to maintain the pluripotency of human embryonic stem cells (hESCs); however, the underlying mechanism remains to be fully understood. Here, we report that silencing of Oct4 in hESCs leads to the activation of tumor suppressor p53, inducing the differentiation of hESCs since acute disruption of p53 in p53 conditional knockout (p53CKO) hESCs prevents the differentiation of hESCs after Oct4 depletion. We further discovered that the silencing of Oct4 significantly reduces the expression of Sirt1, a deacetylase known to inhibit p53 activity and the differentiation of ESCs, leading to increased acetylation of p53 at lysine 120 and 164. The importance of Sirt1 in mediating Oct4-dependent pluripotency is revealed by the finding that the ectopic expression of Sirt1 in Oct4-silenced hESCs prevents p53 activation and hESC differentiation. In addition, using knock-in approach, we revealed that the acetylation of p53 at lysine 120 and 164 is required for both stabilization and activity of p53 in hESCs. In summary, our findings reveal a novel role of Oct4 in maintaining the pluripotency of hESCs by suppressing pathways that induce differentiation. Considering that p53 suppresses pluripotency after DNA damage response in ESCs, our findings further underscore the stringent mechanism to coordinate DNA damage response pathways and pluripotency pathways in order to maintain the pluripotency and genomic stability of hESCs.

Indexed as

AcetylationCell Culture TechniquesCell DifferentiationDNA DamageEmbryonic Stem CellsGene Knockout TechniquesHumansOctamer Transcription Factor-3Pluripotent Stem CellsSirtuin 1TransfectionTumor Suppressor Protein p53Octamer Transcription Factor-3POU5F1 protein, humanSIRT1 protein, humanSirtuin 1TP53 protein, humanTumor Suppressor Protein p53AcetylationDifferentiationDNA damage responseHuman ESCsp53Pluripotency

Identifiers

PMID24038750
PMCPMC3947311
OpenAlexW1594575326

What OpenQuestion holds

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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.