The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Suppression of induced pluripotent stem cell generation by the p53–p21 pathway
Open accessAbstract
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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Self-citationInduction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
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Self-citationInduced Pluripotent Stem Cell Lines Derived from Human Somatic Cells
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Generation of germline-competent induced pluripotent stem cells
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Self-citationIn vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state
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Reprogramming of human somatic cells to pluripotency with defined factors
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Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts
Nakagawa, M., Koyanagi, M., Tanabe, K., Takahashi, K., Ichisaka, T., Aoi, T., Okita, K., Mochiduki, Y., Takizawa, N., & Yamanaka, S. (2008) · Nature Biotechnology · doi:10.1038/nbt1374 · Cited by 2,380
Self-citationGeneration of Mouse Induced Pluripotent Stem Cells Without Viral Vectors
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Plat-E: an efficient and stable system for transient packaging of retroviruses
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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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