Obiettivo Tetralogy of Fallot (TOF) is the most common congenital heart disease (CHD) occurring 1 in 3000 births. Genetic studies have identified numerous genes that are responsible for inherited and sporadic forms of TOF, most of which encode key molecules that are part of regulatory networks controlling heart development. The identification of two populations of cardiac precursors, one exclusively forming the left ventricle and the second the outflow tract, the right ventricle and the atria, has suggested a new approach to interpret CHDs, in particular in TOF, not as a defect in a specific gene, but rather as a defect in the formation, expansion, and differentiation of defined subsets of embryonic cardiac precursors. The LIM-homeodomain transcription factor ISL1 marks the second population of cardiac progenitors, but little is known about its downstream targets, and how causative genes of CHDs affect cell-fate decisions in the ISL1 lineage. The main goals of this research program are: (1) to decipher the functional role of Isl1 downstream targets identified by a genome-wide ChIP-Seq approach; (2) to generate induced pluripotent stem (iPS) cells from controls and patients affected by severe forms of TOF characterized by defects in heart compartments known to derive from ISL1 cardiac progenitors; (3) to direct these iPS cells to ISL1+ cardiovascular precursors and identify cell-surface makers enabling their antibody-based purification; and (4) to use TOF-iPS-derived ISL1+ progenitors as an unique in vitro model system for deciphering molecular mechanisms that govern the fates and differentiation of this progenitor lineage and determine the pathological phenotype seen in TOF. This work will shed light on the molecular mechanisms of ISL1+ cardiac progenitor lineage specification and will give important new insights into the mechanisms of how alterations in transcriptional and epigenetic programs translate to a distinct structural defect during cardiogenesis. Campo scientifico medical and health sciencesclinical medicinecardiologypaediatric cardiology Programma(i) 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) Argomento(i) ERC-SG-LS4 - ERC Starting Grant - Physiology, Pathophysiology and Endocrinology Invito a presentare proposte ERC-2010-StG_20091118 Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-SG - ERC Starting Grant Istituzione ospitante KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN Contributo UE € 1 499 996,25 Indirizzo ISMANINGER STRASSE 22 81675 Muenchen Germania Mostra sulla mappa Regione Bayern Oberbayern München, Kreisfreie Stadt Tipo di attività Higher or Secondary Education Establishments Ricercatore principale Karl-Ludwig Laugwitz (Prof.) Contatto amministrativo Beate Schaulin (Mrs.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN Germania Contributo UE € 1 499 996,25 Indirizzo ISMANINGER STRASSE 22 81675 Muenchen Mostra sulla mappa Regione Bayern Oberbayern München, Kreisfreie Stadt Tipo di attività Higher or Secondary Education Establishments Ricercatore principale Karl-Ludwig Laugwitz (Prof.) Contatto amministrativo Beate Schaulin (Mrs.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato