Apoptosis and failure of checkpoint kinase 1 activation in human induced pluripotent stem cells under replication stress

Human 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...

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Bibliographic Details
Published in:Stem cell research & therapy 2016-01, Vol.7 (17), p.17-17, Article 17
Main Authors: Desmarais, Joelle A, Unger, Christian, Damjanov, Ivan, Meuth, Mark, Andrews, Peter
Format: Article
Language:English
Subjects:
Analysis
Animals
Apoptosis
Care and treatment
Checkpoint Kinase 1
Complications and side effects
DNA Replication
HCT116 Cells
Humans
Induced Pluripotent Stem Cells - physiology
Infection
Mice
Protein Kinases - metabolism
Short Report
Stem cell research
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Summary:Human 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. Here 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. We 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. Together, 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.
ISSN:1757-6512
1757-6512
DOI:10.1186/s13287-016-0279-2