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

Nature | Aug 27, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19668191

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 RIS Download

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

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Associated grants

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

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