2011
DOI: 10.1038/cdd.2011.9
|View full text |Cite
|
Sign up to set email alerts
|

Genomic instability in induced stem cells

Abstract: The ability to reprogram adult cells into stem cells has raised hopes for novel therapies for many human diseases. Typical stem cell reprogramming protocols involve expression of a small number of genes in differentiated somatic cells with the c-Myc and Klf4 protooncogenes typically included in this mix. We have previously shown that expression of oncogenes leads to DNA replication stress and genomic instability, explaining the high frequency of p53 mutations in human cancers. Consequently, we wondered whether… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1

Citation Types

4
116
0
5

Year Published

2011
2011
2018
2018

Publication Types

Select...
7
2

Relationship

0
9

Authors

Journals

citations
Cited by 138 publications
(131 citation statements)
references
References 46 publications
4
116
0
5
Order By: Relevance
“…[52][53][54] The same is true for the facts, that the epigenetic memory of the original differentiated state is not perfectly erased during reprogramming 55,56 and that iPS cells have been reported to accumulate karyotypic abnormalities and gene mutations during propagation in culture. [57][58][59][60] AFS very likely do not harbour accumulated somatic mutations, because they are primary cells of a very early stage of human development. Furthermore, monoclonal human AFS cell lines have been reported to maintain genome stability during expansion and do not induce tumour formation in severe combined immunodeficient mice.…”
Section: Amniotic Fluid Stem (Afs) Cells Could Be a Useful Tool To Stmentioning
confidence: 99%
“…[52][53][54] The same is true for the facts, that the epigenetic memory of the original differentiated state is not perfectly erased during reprogramming 55,56 and that iPS cells have been reported to accumulate karyotypic abnormalities and gene mutations during propagation in culture. [57][58][59][60] AFS very likely do not harbour accumulated somatic mutations, because they are primary cells of a very early stage of human development. Furthermore, monoclonal human AFS cell lines have been reported to maintain genome stability during expansion and do not induce tumour formation in severe combined immunodeficient mice.…”
Section: Amniotic Fluid Stem (Afs) Cells Could Be a Useful Tool To Stmentioning
confidence: 99%
“…Une autre explication pourrait être que la reprogrammation crée un stress réplicatif qui serait à l'origine des aberrations génétiques. Effectivement, un certain nombre des altérations de l'ADN se concentrent dans des régions fragiles du génome connues pour être altérées en cas de stress réplicatif, lequel peut être induit par un oncogène comme c-myc [10]. Ces observations sont en accord avec le fait que les systèmes de protection du génome contre la transformation maligne -p53, p16/ Ink4a et p19/Arf -sont les mêmes qui bloquent en partie la reprogrammation [11].…”
Section: La Défianceunclassified
“…In this respect, reprogramming of somatic mouse cells results in replication stress, which is in part dependent on c-Myc. 5 This would explain the positive effect of p53 loss on reprogramming efficiency. 6 But why this effect is not observed in the context of DNA ligase IV inhibition (this study)?…”
mentioning
confidence: 99%