• DOI:10.1038/nature08235
• Corpus ID: 4384280

Suppression of induced pluripotent stem cell generation by the p53–p21 pathway

@article{Hong2009SuppressionOI,
  title={Suppression of induced pluripotent stem cell generation by the p53–p21 pathway},
  author={Hyenjong Hong and Kazutoshi Takahashi and Tomoko Ichisaka and Takashi Aoi and Osami Kanagawa and Masato Nakagawa and Keisuke Okita and Shinya Yamanaka},
  journal={Nature},
  year={2009},
  volume={460},
  pages={1132-1135}
}

• Hyenjong Hong, Kazutoshi Takahashi, +5 authors S. Yamanaka
• Published 27 August 2009
• Biology
• Nature

Induced pluripotent stem (iPS) cells can be generated from somatic cells by the introduction of Oct3/4 (also known as Pou5f1), Sox2, Klf4 and c-Myc, in mouse and in human. The efficiency of this process, however, is low. Pluripotency can be induced without c-Myc, but with even lower efficiency. A p53 (also known as TP53 in humans and Trp53 in mice) short-interfering RNA (siRNA) was recently shown to promote human iPS cell generation, but the specificity and mechanisms remain to be determined. Here we report that up to 10% of transduced mouse embryonic fibroblasts lacking p53 became iPS cells, even without the Myc retrovirus. The p53 deletion also promoted the induction of integration-free mouse iPS cells with plasmid transfection. Furthermore, in the p53-null background, iPS cells were generated from terminally differentiated T lymphocytes. The suppression of p53 also increased the efficiency of human iPS cell generation. DNA microarray analyses identified 34 p53-regulated genes that are common in mouse and human fibroblasts. Functional analyses of these genes demonstrate that the p53–p21 pathway serves as a barrier not only in tumorigenicity, but also in iPS cell generation.