Cited by 1,301Pluripotent Stem Cells ResearchDevelopmental Biology and Gene RegulationNeurogenesis and neuroplasticity mechanisms

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

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Hong, Hyenjong, Takahashi, Kazutoshi, Ichisaka, Tomoko, Aoi, Takashi, Kanagawa, Osami, Nakagawa, Masato, Okita, Keisuke, Yamanaka, Shinya·2009·Nature

DOI 10.1038/nature08235PMC PMC2917235

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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.

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Authors: Hong, H., Takahashi, K., Ichisaka, T., Aoi, T., Kanagawa, O., Nakagawa, M., Okita, K., & Yamanaka, S.
Affiliations: Kyoto University (JP)
RIKEN (JP)
Gladstone Institutes (US)
Corresponding author: Yamanaka, Shinya
ORCID: Takahashi, Kazutoshi
Aoi, Takashi
Kanagawa, Osami
Nakagawa, Masato
Okita, Keisuke
Yamanaka, Shinya
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2009-08
Volume: 460
Issue: 7259
Pages: 1132-1135
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature08235
PMC: PMC2917235
OpenAlex: W2081620485
Cited by: 1,301
References: 23
Citations by year: 2026: 13 · 2025: 16 · 2024: 25 · 2023: 29 · 2022: 44 · 2021: 51 · 2020: 41 · 2019: 56 · 2018: 63 · 2017: 59 · 2016: 78 · 2015: 88 · 2014: 116 · 2013: 117 · 2012: 168
FWCI: 67.71
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
Funders: National Heart, Lung, and Blood Institute (U01HL100406)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords: induced pluripotent stem cells, p53, p21, p53/p21 pathway, reprogramming efficiency, mouse embryonic fibroblasts, T cells, plasmid transfection, p53 target genes, tumorigenicity, Oct4, SOX2, KLF4, c-Myc
MeSH terms: Kruppel-Like Factor 4, Adult, Animals, Cell Differentiation, Embryo, Mammalian, Female, Fibroblasts, Humans, Male, Plasmids, T-Lymphocytes, Transfection, Tumor Suppressor Protein p53, Genes, myc, Oligonucleotide Array Sequence Analysis, Gene Silencing, Gene Expression Profiling, Pluripotent Stem Cells, Cyclin-Dependent Kinase Inhibitor p21, Mice

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

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