Original Article

Citation: Cell Death and Disease (2016) 7, e2567; doi:10.1038/cddis.2016.419
Published online 29 December 2016

Differential regulated microRNA by wild type and mutant p53 in induced pluripotent stem cells
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Francesca Grespi1, Vivien Landré2, Alina Molchadsky3, Nicola Di Daniele4, Luigi Tonino Marsella4, Gerry Melino2,4 and Varda Rotter3

  1. 1Department of Biology, University of Padua, Padua, Italy
  2. 2Medical Research Council, Toxicology Unit, Leicester University, Hodgkin Building, Leicester, UK
  3. 3Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
  4. 4Faculty of Medicine and Surgery, University of Rome 'Tor Vergata', Rome, Italy

Correspondence: G Melino, Medical Research Council, Toxicology Unit, Leicester University, Lancaster Road, PO Box 138, Hodgkin Building, Leicester LE1 9HN, UK. Tel: +44 0 116 252 5551; Fax: +39 06 72596977; E-mail: gm89@leicester.ac.uk; V Rotter, Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel. Tel: +972 8 9344501; Fax: +972 8 934 2398; E-mail: varda.rotter@weizmann.ac.il

Received 3 October 2016; Revised 11 October 2016; Accepted 12 October 2016

Edited by G Raschella

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Abstract

The tumour suppressor p53 plays an important role in somatic cell reprogramming. While wild-type p53 reduces reprogramming efficiency, mutant p53 exerts a gain of function activity that leads to increased reprogramming efficiency. Furthermore, induced pluripotent stem cells expressing mutant p53 lose their pluripotency in vivo and form malignant tumours when injected in mice. It is therefore of great interest to identify targets of p53 (wild type and mutant) that are responsible for this phenotype during reprogramming, as these could be exploited for therapeutic use, that is, formation of induced pluripotent stem cells with high reprogramming efficiency, but no oncogenic potential. Here we studied the transcriptional changes of microRNA in a series of mouse embryonic fibroblasts that have undergone transition to induced pluripotent stem cells with wild type, knock out or mutant p53 status in order to identify microRNAs whose expression during reprogramming is dependent on p53. We identified a number of microRNAs, with known functions in differentiation and carcinogenesis, the expression of which was dependent on the p53 status of the cells. Furthermore, we detected several uncharacterised microRNAs that were regulated differentially in the different p53 backgrounds, suggesting a novel role of these microRNAs in reprogramming and pluripotency.