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

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.

Pubmed ID: 19668191


  • Hong H
  • Takahashi K
  • Ichisaka T
  • Aoi T
  • Kanagawa O
  • Nakagawa M
  • Okita K
  • Yamanaka S



Publication Data

August 27, 2009

Associated Grants

  • Agency: NHLBI NIH HHS, Id: U01 HL100406
  • Agency: NHLBI NIH HHS, Id: U01 HL100406-01

Mesh Terms

  • Adult
  • Animals
  • Cell Differentiation
  • Cyclin-Dependent Kinase Inhibitor p21
  • Embryo, Mammalian
  • Female
  • Fibroblasts
  • Gene Expression Profiling
  • Gene Silencing
  • Genes, myc
  • Humans
  • Male
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Plasmids
  • Pluripotent Stem Cells
  • T-Lymphocytes
  • Transfection
  • Tumor Suppressor Protein p53