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


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Article Info

DATE

2009-08

AUTHORS

Hyenjong Hong, Kazutoshi Takahashi, Tomoko Ichisaka, Takashi Aoi, Osami Kanagawa, Masato Nakagawa, Keisuke Okita, Shinya Yamanaka

ABSTRACT

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. More... »

PAGES

1132

Journal

TITLE

Nature

ISSUE

7259

VOLUME

460

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature08235

    DOI

    http://dx.doi.org/10.1038/nature08235

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1015108174

    PUBMED

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


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