ArticleStem cell research & therapy2016
Apoptosis and failure of checkpoint kinase 1 activation in human induced pluripotent stem cells under replication stress.
Article in Stem cell research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 51 citations in OpenAlex.
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- Feeder-free culture of human pluripotent stem cells drives MDM4-mediated gain of chromosome 1q.Stem cell reports · 2024Article
- The origins of human pluripotent stem cells: the road from a cancer to regenerative medicine.In vitro cellular & developmental biology. Animal · 2024Review
- Replication stress causes delayed mitotic entry and chromosome 12 fragility at the ANKS1B large neuronal gene in human induced pluripotent stem cells.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2023Article
- Thymidine nucleotide metabolism controls human telomere length.Nature genetics · 2023Article
- Human Induced Pluripotent Stem Cells: From Cell Origin, Genomic Stability, and Epigenetic Memory to Translational Medicine.Stem cells (Dayton, Ohio) · 2022Review
- Single cell heterogeneity in human pluripotent stem cells.BMB reports · 2021Article
- SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export: genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis.Molecular neurodegeneration · 2021Article
- Defining the signalling determinants of a posterior ventral spinal cord identity in human neuromesodermal progenitor derivatives.Development (Cambridge, England) · 2021Article
- Acquired genetic changes in human pluripotent stem cells: origins and consequences.Nature reviews. Molecular cell biology · 2020Review
- Generation and trapping of a mesoderm biased state of human pluripotency.Nature communications · 2020Article
- Mthfd2 Modulates Mitochondrial Function and DNA Repair to Maintain the Pluripotency of Mouse Stem Cells.Stem cell reports · 2020Article
- Nucleosides Rescue Replication-Mediated Genome Instability of Human Pluripotent Stem Cells.Stem cell reports · 2020Article
- Generation of Otic Lineages from Integration-Free Human-Induced Pluripotent Stem Cells Reprogrammed by mRNAs.Stem cells international · 2020Article
- Reprogramming and differentiation-dependent transcriptional alteration of DNA damage response and apoptosis genes in human induced pluripotent stem cells.Journal of radiation research · 2019Article
- Article
- Unraveling the Inconsistencies of Cardiac Differentiation Efficiency Induced by the GSK3β Inhibitor CHIR99021 in Human Pluripotent Stem Cells.Stem cell reports · 2018Article
- Transfection of Peripheral Blood Monocytes withStem cells international · 2018Article
- DNA repair mechanisms in embryonic stem cells.Cellular and molecular life sciences : CMLS · 2017Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundHuman induced pluripotent stem (hiPS) cells have the ability to undergo self-renewal and differentiation similarly to human embryonic stem (hES) cells. We have recently shown that hES cells under replication stress fail to activate checkpoint kinase 1 (CHK1). They instead commit to apoptosis, which appears to be a primary defense mechanism against genomic instability. It is not known whether the failure of CHK1 activation and activation of apoptosis under replication stress is solely a feature of hES cells, or if it is a feature that can be extended to hiPS cells.
methodsHere we generated integration-free hiPS cell lines by mRNA transfection, and characterised the cell lines. To investigate the mechanism of S phase checkpoint activation, we have induced replication stress by adding excess thymidine to the cell culture medium, and performed DNA content analysis, apoptosis assays and immunoblottings.
resultsWe are showing that hiPS cells similarly to hES cells, fail to activate CHK1 when exposed to DNA replication inhibitors and commit to apoptosis instead. Our findings also suggest the Ataxia Telangiectasia Mutated pathway might be responding to DNA replication stress, resulting in apoptosis.
conclusionTogether, these data suggest that the apoptotic response was properly restored during reprogramming with mRNA, and that apoptosis is an important mechanism shared by hiPS and hES cells to maintain their genomic integrity when a replication stress occurs.
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