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Suppression of induced pluripotent stem cell generation by the p53–p21 pathway
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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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“It is known that OSKM induction activates the p53–p21 pathway25.”
From In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche (2021) · cites this paper as [25]
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Metadata
- 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
- Venue
- Nature
- Published
- 2009-08
- Volume
- 460
- Issue
- 7259
- Pages
- 1132-1135
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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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