Evidence map›Paper›PMID 25375373›Full record

ArticleCell death & disease2014

CDK1 plays an important role in the maintenance of pluripotency and genomic stability in human pluripotent stem cells.

I Neganova, K Tilgner, A Buskin, I Paraskevopoulou, S P Atkinson, D Peberdy, J F Passos, M Lako

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 13% 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

57 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Embryonic Stem Cell-Specific Responses to DNA Replication Stress.bioRxiv : the preprint server for biology · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Coupling of stemness maintenance with cell cycle control in stem cells.Frontiers in cell and developmental biology · 2025
    Review
  10. Genes as Genome Stabilizers in Pluripotent Stem Cells.Advances in experimental medicine and biology · 2025
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Molecular mechanisms underlying TNFα-induced mitochondrial fragmentation in human airway smooth muscle cells.American journal of physiology. Lung cellular and molecular physiology · 2024
    Article
  17. Article
  18. Article
  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

8 authors at 2 institutions in 1 country.

I NeganovaInstitute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne NE1 3BZ, UK.
K TilgnerInstitute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne NE1 3BZ, UK.
A BuskinInstitute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne NE1 3BZ, UK.
I ParaskevopoulouInstitute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne NE1 3BZ, UK.
S P AtkinsonInstitute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne NE1 3BZ, UK.
D PeberdyInstitute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne NE1 3BZ, UK.
J F PassosCentre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
M LakoInstitute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne NE1 3BZ, UK.
Centre for Life · GBNewcastle University · GB

Funding

Biotechnology and Biological Sciences Research Council BB/E012841/1Biotechnology and Biological Sciences Research Council BB/H022384/1Biotechnology and Biological Sciences Research Council BBS/B/14779
6 · The paper itself

Abstract

Human embryonic stem cells (hESC) and induced pluripotent stem cells (hiPSC) are characterised by an unusual and tightly regulated cell cycle that has been shown to be important for the maintenance of a pluripotent phenotype. Cyclin-dependant kinase 1 (CDK1) is a key player in cell cycle regulation and particularly mitosis; however, its role has not been studied previously in hESC and hiPSC. To investigate the impacts of CDK1 downregulation, we performed RNA interference studies which in addition to expected mitotic deficiencies revealed a large range of additional phenotypes related to maintenance of pluripotency, ability to repair double strand breaks (DSBs) and commitment to apoptosis. Downregulation of CDK1 led to the loss of typical pluripotent stem cell morphology, downregulation of pluripotency markers and upregulation of a large number of differentiation markers. In addition, human pluripotent stem cells with reduced CDK1 expression accumulated a higher number of DSBs were unable to activate CHK2 expression and could not maintain G2/M arrest upon exposure to ionising radiation. CDK1 downregulation led to the accumulation of cells with abnormal numbers of mitotic organelles, multiple chromosomal abnormalities and polyploidy. Furthermore, such cells demonstrated an inability to execute apoptosis under normal culture conditions, despite a significant increase in the expression of active PARP1, resulting in tolerance and very likely further propagation of genomic instabilities and ensuing of differentiation process. On the contrary, apoptosis but not differentiation, was the preferred route for such cells when they were subjected to ionising radiation. Together these data suggest that CDK1 regulates multiple events in human pluripotent stem cells ranging from regulation of mitosis, G2/M checkpoint maintenance, execution of apoptosis, maintenance of pluripotency and genomic stability.

Indexed as

DNA RepairApoptosisBiomarkersCDC2 Protein KinaseCell DifferentiationCell LineCheckpoint Kinase 2Cyclin-Dependent KinasesDNA Breaks, Double-StrandedEmbryonic Stem CellsG2 Phase Cell Cycle CheckpointsGamma RaysGene Expression RegulationGenomic InstabilityHumansInduced Pluripotent Stem CellsBiomarkersCDC2 Protein KinaseCDK1 protein, humanCheckpoint Kinase 2CHEK2 protein, humanCyclin-Dependent KinasesPARP1 protein, humanPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesRNA, Small Interfering

Identifiers

PMID25375373
PMCPMC4260724
OpenAlexW1998347914

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.