title: Differential regulated microRNA by wild type and mutant p53 in induced pluripotent stem cells.
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.
authors.affiliation: Department of Biology, University of Padua, Padua, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Grespi
authors.affiliation: Medical Research Council, Toxicology Unit, Leicester University, Hodgkin Building, Leicester, UK.
authors.forename: Vivien
authors.initials: V
authors.lastname: Landré
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Alina
authors.initials: A
authors.lastname: Molchadsky
authors.affiliation: Faculty of Medicine and Surgery, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Di Daniele
authors.affiliation: Faculty of Medicine and Surgery, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: Luigi Tonino
authors.initials: LT
authors.lastname: Marsella
authors.affiliation: Medical Research Council, Toxicology Unit, Leicester University, Hodgkin Building, Leicester, UK.|Faculty of Medicine and Surgery, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: Gerry
authors.initials: G
authors.lastname: Melino
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Varda
authors.initials: V
authors.lastname: Rotter
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D020218:Response Elements / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53