Linking the p53 tumour suppressor pathway to somatic cell reprogramming View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-08

AUTHORS

Teruhisa Kawamura, Jotaro Suzuki, Yunyuan V. Wang, Sergio Menendez, Laura Batlle Morera, Angel Raya, Geoffrey M. Wahl, Juan Carlos Izpisúa Belmonte

ABSTRACT

Reprogramming somatic cells to induced pluripotent stem (iPS) cells has been accomplished by expressing pluripotency factors and oncogenes, but the low frequency and tendency to induce malignant transformation compromise the clinical utility of this powerful approach. We address both issues by investigating the mechanisms limiting reprogramming efficiency in somatic cells. Here we show that reprogramming factors can activate the p53 (also known as Trp53 in mice, TP53 in humans) pathway. Reducing signalling to p53 by expressing a mutated version of one of its negative regulators, by deleting or knocking down p53 or its target gene, p21 (also known as Cdkn1a), or by antagonizing reprogramming-induced apoptosis in mouse fibroblasts increases reprogramming efficiency. Notably, decreasing p53 protein levels enabled fibroblasts to give rise to iPS cells capable of generating germline-transmitting chimaeric mice using only Oct4 (also known as Pou5f1) 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. More... »

PAGES

1140

Journal

TITLE

Nature

ISSUE

7259

VOLUME

460

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature08311

DOI

http://dx.doi.org/10.1038/nature08311

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1040491383

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19668186


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N-Triples is a line-based linked data format ideal for batch operations.

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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

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325 schema:name Center of Regenerative Medicine in Barcelona, Dr. Aiguader 88, 08003 Barcelona, Spain
326 Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
327 rdf:type schema:Organization
 




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