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Linking the p53 tumor suppressor pathway to somatic cell reprogramming
Reprogramming somatic cells to induced pluripotent stem (iPS) cells has been accomplished by expressing pluripotency factors and oncogenes1–8, but the low frequency and tendency to induce malignant transformation9 compromise the clinical utility of this powerful approach. We address both issues by i...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735889/ https://www.ncbi.nlm.nih.gov/pubmed/19668186 http://dx.doi.org/10.1038/nature08311 |
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author | Kawamura, Teruhisa Suzuki, Jotaro Wang, Yunyuan V. Menendez, Sergio Morera, Laura Batlle Raya, Angel Wahl, Geoffrey M. Belmonte, Juan Carlos Izpisúa |
author_facet | Kawamura, Teruhisa Suzuki, Jotaro Wang, Yunyuan V. Menendez, Sergio Morera, Laura Batlle Raya, Angel Wahl, Geoffrey M. Belmonte, Juan Carlos Izpisúa |
author_sort | Kawamura, Teruhisa |
collection | PubMed |
description | Reprogramming somatic cells to induced pluripotent stem (iPS) cells has been accomplished by expressing pluripotency factors and oncogenes1–8, but the low frequency and tendency to induce malignant transformation9 compromise the clinical utility of this powerful approach. We address both issues by investigating the mechanisms limiting reprogramming efficiency in somatic cells. We show that reprogramming factors can activate the p53 pathway. Reducing signaling to p53 by expressing a mutated version of one of its negative regulators, by deleting or silencing p53 or its target gene, p21, or by antagonizing apoptosis enhanced three factor (Oct4/Sox2/Klf4)-mediated reprogramming of mouse fibroblasts. Notably, decreasing p53 protein levels enabled fibroblasts to give rise to iPS cells capable of generating germline transmitting chimeric mice using only Oct4 and Sox2. Furthermore, silencing of p53 significantly increased the reprogramming efficiency of human somatic cells. These results provide insights into reprogramming mechanisms and suggest new routes to more efficient reprogramming while minimizing the use of oncogenes. |
format | Text |
id | pubmed-2735889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
record_format | MEDLINE/PubMed |
spelling | pubmed-27358892010-02-27 Linking the p53 tumor suppressor pathway to somatic cell reprogramming Kawamura, Teruhisa Suzuki, Jotaro Wang, Yunyuan V. Menendez, Sergio Morera, Laura Batlle Raya, Angel Wahl, Geoffrey M. Belmonte, Juan Carlos Izpisúa Nature Article Reprogramming somatic cells to induced pluripotent stem (iPS) cells has been accomplished by expressing pluripotency factors and oncogenes1–8, but the low frequency and tendency to induce malignant transformation9 compromise the clinical utility of this powerful approach. We address both issues by investigating the mechanisms limiting reprogramming efficiency in somatic cells. We show that reprogramming factors can activate the p53 pathway. Reducing signaling to p53 by expressing a mutated version of one of its negative regulators, by deleting or silencing p53 or its target gene, p21, or by antagonizing apoptosis enhanced three factor (Oct4/Sox2/Klf4)-mediated reprogramming of mouse fibroblasts. Notably, decreasing p53 protein levels enabled fibroblasts to give rise to iPS cells capable of generating germline transmitting chimeric mice using only Oct4 and Sox2. Furthermore, silencing of p53 significantly increased the reprogramming efficiency of human somatic cells. These results provide insights into reprogramming mechanisms and suggest new routes to more efficient reprogramming while minimizing the use of oncogenes. 2009-08-09 2009-08-27 /pmc/articles/PMC2735889/ /pubmed/19668186 http://dx.doi.org/10.1038/nature08311 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Kawamura, Teruhisa Suzuki, Jotaro Wang, Yunyuan V. Menendez, Sergio Morera, Laura Batlle Raya, Angel Wahl, Geoffrey M. Belmonte, Juan Carlos Izpisúa Linking the p53 tumor suppressor pathway to somatic cell reprogramming |
title | Linking the p53 tumor suppressor pathway to somatic cell reprogramming |
title_full | Linking the p53 tumor suppressor pathway to somatic cell reprogramming |
title_fullStr | Linking the p53 tumor suppressor pathway to somatic cell reprogramming |
title_full_unstemmed | Linking the p53 tumor suppressor pathway to somatic cell reprogramming |
title_short | Linking the p53 tumor suppressor pathway to somatic cell reprogramming |
title_sort | linking the p53 tumor suppressor pathway to somatic cell reprogramming |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735889/ https://www.ncbi.nlm.nih.gov/pubmed/19668186 http://dx.doi.org/10.1038/nature08311 |
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