Objective Hematopoietic Stem Cell (HSC)-based therapies are becoming a great expectation for the cure of several disorders that require HSCs for treatment. However, the incapacity to generate and maintain fully potent transplantable HSCs in vitro is still nowadays one of the main limitations for their wide application in cellular therapies. The study of the molecular mechanisms underlying HSC ontogeny in embryos is thus of crucial importance in order to elucidate the genetic networks that control the emergence and expansion of these cells.HSCs are first and possibly entirely formed in arterial-endothelium during embryonic life, a process dependent on Notch-signalling. However, the molecular events regulating these signals are mainly unknown.Fringe-glycosyltransferases are Notch modifiers contributing to the differential response of Notch to distinct ligands. It is hypothesized that the cross-talk between Notch and its cognate ligands in the arterial endothelium compartment is primarily a consequence of Fringe-mediated modification and the driving-force towards endothelium-HSC transition.This project aims the elucidation of the role Fringe as modulators of Notch-signalling towards specification of HSC identity at mid-gestation mouse embryos, an issue that has not been addressed so far. This work will be initiated with the identification of the Fringe involved on HSC emergence and with the study on how the modulation of their expression is correlated with Notch-ligand responsiveness and formation of hematopoietic precursors in vitro. The results obtained in this part of the project will be the basis of further in vivo experiments, using Fringe knock-in and knock-out animal models.The execution of this proposal should provide relevant clues on important biological questions involving stemness and cell differentiation. Moreover, it will pave the way for the development of new and more robust strategies to produce and expand HSCs a crucial issue for regenerative medicine. Fields of science medical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineembryology 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) Topic(s) FP7-PEOPLE-2011-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Call for proposal FP7-PEOPLE-2011-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator FUNDACIO INSTITUT HOSPITAL DEL MAR D INVESTIGACIONS MEDIQUES Address Doctor aiguader 88 08003 Barcelona Spain See on map Region Este Cataluña Barcelona Activity type Research Organisations Administrative Contact Andreu Fort (Mr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data
