ROADTOIPS
Dissection of molecular signature transformation during the process of pluripotency induction
| Coordinatore | THE UNIVERSITY OF EDINBURGH
Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie. |
| Nazionalità Coordinatore | United Kingdom [UK] |
| Totale costo | 1˙359˙000 € |
| EC contributo | 1˙359˙000 € |
| Programma | 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) |
| Code Call | ERC-2010-StG_20091118 |
| Funding Scheme | ERC-SG |
| Anno di inizio | 2010 |
| Periodo (anno-mese-giorno) | 2010-12-01 - 2015-11-30 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
THE UNIVERSITY OF EDINBURGH
Organization address
address: OLD COLLEGE, SOUTH BRIDGE contact info |
UK (EDINBURGH) | hostInstitution | 1˙359˙000.00 |
| 2 |
THE UNIVERSITY OF EDINBURGH
Organization address
address: OLD COLLEGE, SOUTH BRIDGE contact info |
UK (EDINBURGH) | hostInstitution | 1˙359˙000.00 |
Mappa
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Obiettivo del progetto (Objective)
'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.'