English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Reprogramming of the somatic state to pluripotency can be induced by a defined set of transcription factors including Oct3/4, Sox2, Klf4, and c‐Myc [Cell 2006;126:663‐676]. These induced pluripotent stem cells (iPSCs) hold great promise in human therapy and disease modeling. However, tumor suppressive activities of p53, which are necessary to prevent persistence of DNA damage in mammalian cells, have proven a serious impediment to formation of iPSCs [Nat Methods 2011;8:409‐412]. We examined the requirement for downstream p53 activities in suppressing efficiency of reprogramming as well as preventing persistence of DNA damage into the early iPSCs. We discovered that the majority of the p53 activation occurred through early reprogramming‐induced DNA damage with the activated expression of the apoptotic inducer  Puma  and the cell cycle inhibitor  p21 . While Puma deficiency increases reprogramming efficiency only in the absence of c‐Myc, double deficiency of  Puma  and  p21  has achieved a level of efficiency that exceeded that of  p53  deficiency alone. We further demonstrated that, in both the presence and absence of p21, Puma deficiency was able to prevent any increase in persistent DNA damage in early iPSCs. This may be due to a compensatory cellular senescent response to reprogramming‐induced DNA damage in pre‐iPSCs. Therefore, our findings provide a potentially safe approach to enhance iPSC derivation by transiently silencing  Puma  and  p21  without compromising genomic integrity. S TEM  C ELLS   2012;30:888–897

Context‐Dependent Enhancement of Induced Pluripotent Stem Cell Reprogramming by Silencing Puma