Objectif Induced pluripotent stem cells (iPSCs) are expected to have an enormous impact on medical research. However, the efficiency of reprogramming is still low and far from routine. Nevertheless, reprogramming with defined factors, Oct4, Sox2, Klf4 and c-Myc, is not a random event. Cells positive for SSEA-1, a marker of undifferentiated mouse ES cells (ESC), appear from cells which have lost the fibroblast marker Thy-1, prior to acquiring other pluripotent markers, e.g. Oct4, Nanog. Similarly, TRA-1-60 positive fully reprogrammed human iPSCs appear from SSEA-4 positive populations. Based on these observations, I hypothesize that there are essential ordered stages that the cells must undergo as they are directed toward pluripotency.To explore this hypothesis, I plan to perform three projects:1. Identifying gene expression signatures during the successful reprogramming process.2. Investigating serial changes of reprogramming factor binding, chromatin modifications and chromatin structure on the route to a pluripotent state.3. Functional analysis of the candidate gene(s) identified for successful reprogramming.Based on my latest publication in Nature, I have developed an original highly efficient reprogramming system, in which almost all cells differentiated by retinoic acid treatment generate iPSCs by day 12 post reprogramming factor induction. The homogenous culture allowed by this system enables the unique execution of the objectives above, and for the first time will shed light on the molecular mechanisms of the reprogramming process. Accurate and more informed understanding of these ordered processes will allow derivation of strategies to improve the reprogramming technology. Champ scientifique medical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesmathematicspure mathematicsmathematical analysisfunctional analysis Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-SG-LS3 - ERC Starting Grant - Cellular and Developmental Biology Appel à propositions ERC-2010-StG_20091118 Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil THE UNIVERSITY OF EDINBURGH Contribution de l’UE € 1 359 000,00 Adresse OLD COLLEGE, SOUTH BRIDGE EH8 9YL Edinburgh Royaume-Uni Voir sur la carte Région Scotland Eastern Scotland Edinburgh Type d’activité Higher or Secondary Education Establishments Chercheur principal Keisuke Kaji (Dr.) Contact administratif Angela Noble (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire THE UNIVERSITY OF EDINBURGH Royaume-Uni Contribution de l’UE € 1 359 000,00 Adresse OLD COLLEGE, SOUTH BRIDGE EH8 9YL Edinburgh Voir sur la carte Région Scotland Eastern Scotland Edinburgh Type d’activité Higher or Secondary Education Establishments Chercheur principal Keisuke Kaji (Dr.) Contact administratif Angela Noble (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
