The well known molecule p53 serves not only as a tumour suppressor, but also acts as a barrier to the generation of induced pluripotent stem (iPS) cells. Five papers online in Nature show that when p53 is removed from cell populations that often fail to reprogram there is a higher degree of success.
The iPS cell field is fast moving -- just three years ago stem cells were created from fibroblasts thanks to the insertion of four viral factors. Teams have tweaked the method, removing one or more of those factors.
Shinya Yamanaka and colleagues managed to induce pluripotency in cells lacking p53 even without one of the four factors, and using a method that avoids genome integration of the factors.
Juan Carlos Izpisua Belmonte and co-workers also demonstrate that reprogramming in the absence of oncogenes such as c-Myc and Klf4 occurs more efficiently when inactivating both p53 and another tumour suppressor.
Another team led by Konrad Hochedlinger show that deletion of p53 in populations that do not reprogram rescues their ability to produce iPS cells, and that very high efficiencies can be achieved using immortalized cell lines that lack p53.
Maria Blasco and colleagues show that p53 is critically involved in preventing the reprogramming of cells carrying various types of DNA damage, including short telomeres. They go on to demonstrate that eliminating p53 allows efficient reprogramming even when there is DNA damage.
Meanwhile Manuel Serrano and his team look at a tumour suppressor locus and report that the locus limits reprogramming. Furthermore, ageing has an effect on this locus, which means reprogramming is less efficient in cells from older organisms.
Shinya Yamanaka (Kyoto University, Japan)(DOI: nature08235)
Juan Carlos Izpisua Belmonte (The Salk Institute, La Jolla, CA, USA)(DOI: nature08311)
Konrad Hochedlinger (Massachusetts General Hospital, Boston, MA, USA)(DOI: nature08285)
Maria Blasco Spanish (National Cancer Research Centre, Madrid, Spain)(DOI: nature08287)
Manuel Serrano (Spanish National Cancer Research Center, Madrid, Spain)(DOI: nature08290)
Abstracts available online:
Abstract of Paper 1.
Abstract of Paper 2.
Abstract of Paper 3.
Abstract of Paper 4.
Abstract of Paper 5.
(C) Nature press release.
Message posted by: Trevor M. D'Souza