Article ; Online: Linking the p53 tumour suppressor pathway to somatic cell reprogramming.
2009 Volume 460, Issue 7259, Page(s) 1140–1144
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 ... ...
| 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. |
|||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MeSH term(s) | Animals ; Cells, Cultured ; Cellular Reprogramming/physiology ; Cyclin-Dependent Kinase Inhibitor p21/deficiency ; Cyclin-Dependent Kinase Inhibitor p21/genetics ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Down-Regulation ; Embryo, Mammalian/cytology ; Female ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Humans ; Keratinocytes ; Male ; Mice ; Mice, Inbred C57BL ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/metabolism ; Tumor Suppressor Protein p53/deficiency ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism | |||||||||||||||
| Chemical Substances | Cyclin-Dependent Kinase Inhibitor p21 ; Tumor Suppressor Protein p53 | |||||||||||||||
| Language | English | |||||||||||||||
| Publishing date | 2009-08-09 | |||||||||||||||
| Publishing country | England | |||||||||||||||
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't | |||||||||||||||
| ZDB-ID | 120714-3 | |||||||||||||||
| ISSN | 1476-4687 ; 0028-0836 | |||||||||||||||
| ISSN (online) | 1476-4687 | |||||||||||||||
| ISSN | 0028-0836 | |||||||||||||||
| DOI | 10.1038/nature08311 | |||||||||||||||
| Shelf mark |
|
|||||||||||||||
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 26: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
|||
| Zs.MG 9: Show issues | ||||
| Zs.MO 244: Show issues |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.