Objectif "Adult, embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) possess the fundamental properties to self-renew while remaining pluripotent. These unique capacities are regulated by gene networks which expression is tightly controlled at the epigenetic, transcriptional and post-transcriptional levels to insure proper stem cell fate decisions in response to developmental or environmental cues. Alterations of these networks in cancer stem cells (CSC) support their tumorigenic activity. Therefore, defining the molecular pathways that control the maintenance of self-renewal and pluripotency is not only important to understand normal development but could also improve the clinical potential of adult stem cells, ESCs and iPSCs, and reveal novel strategies to target CSCs.Our objective is to identify novel mechanisms controlling the genetic programs that define the fate of ESCs. Along this line, we recently revealed a central role for alternative splicing (AS) in the regulation of the core ESC pluripotency regulatory circuitry. AS affects over 95% of multi-exon human genes and regulates gene expression by promoting transcriptome and proteome diversity. Although ESCs display a high degree of transcriptome complexity and express a large number of isoforms of unknown function, the extent and significance of AS contribution to this functional diversity remain largely unclear.We propose to characterize molecular pathways that modulate AS programs and reshape the landscape of gene regulation which controls the pluripotency and self-renewal capacities of stem cells. More precisely, we will:1- Identify splicing factors that control conserved AS events in mouse ESCs and support the maintenance self-renewal and pluripotency;2- Characterize AS and gene networks coordinated by these essential factors to reshape the transcriptome of mouse ESCs;3- Define the regulatory code underlying the in vivo regulation of ESC-specific AS networks by these splicing factors." Champ scientifique natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncology Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2013-CIG - Marie-Curie Action: "Career Integration Grants" Appel à propositions FP7-PEOPLE-2013-CIG Voir d’autres projets de cet appel Régime de financement MC-CIG - Support for training and career development of researcher (CIG) Coordinateur INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Contribution de l’UE € 100 000,00 Adresse RUE DE TOLBIAC 101 75654 Paris France Voir sur la carte Région Ile-de-France Ile-de-France Paris Type d’activité Research Organisations Contact administratif Dominique Pella (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
