Cel MicroRNAs (miRNAs) are non-coding RNA molecules that repress translation and stability of target mRNAs. They are key regulators of cell cycle and differentiation in embryonic stem cells, and are differentially expressed among many tumors, but their function in adult stem cells (SC) is not known. Somatic SC are able to self-renew, at the same time generating a differentiated progeny that replenish short-lived cells, to maintain tissue homeostasis. However, how the balance between self-renewal and differentiation is achieved, crucial to avoid SC exhaustion or hyper-proliferation and cancer, has not been fully clarified, including any role for miRNAs. The applicant previously demonstrated that in the absence of the proto-oncogene Pbx1 hematopoietic stem cells (HSCs) display reduced self-renewal, high proliferation rate, a transcriptional profile typical of downstream progeny, and perturbed Tgf-b pathway. In this proposal the applicant will take advantage of the Pbx1-conditional ko mouse model to identify miRNAs involved in the maintenance of self-renewal, through combination of miRNA profiling data of purified HSCs and downstream progenitors from mutant or control mice with mRNA expression data and with miRNA:mRNA target prediction. The role of specific miRNAs regulating self-renewal will then be tested functionally in normal and mutant HSCs, in transplantation assays after over-expression or knock down experiments. Moreover, this study offers the opportunity to identify new players in the Tgf-b pathway, which has been suggested to regulate processing of specific miRNAs in other cell types. Preliminary data indicate that in the absence of Pbx1 several miRNAs are indeed differentially regulated in HSCs, underlying the feasibility of this project. The expected results will have a profound impact on European competitiveness since they address fundamental questions in adult stem cell biology, with potential implications in the fields of regenerative medicine and cancer. Dziedzina nauki natural sciencesbiological sciencescell biologymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologymedical and health sciencesclinical medicinetransplantationmedical and health sciencesbasic medicinephysiologyhomeostasis Program(-y) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Zaproszenie do składania wniosków FP7-PEOPLE-2009-RG Zobacz inne projekty w ramach tego zaproszenia System finansowania MC-IRG - International Re-integration Grants (IRG) Koordynator HUMANITAS MIRASOLE SPA Wkład UE € 100 000,00 Adres VIA MANZONI 56 20100 Rozzano (Mi) Włochy Zobacz na mapie Region Nord-Ovest Lombardia Milano Rodzaj działalności Private for-profit entities (excluding Higher or Secondary Education Establishments) Kontakt administracyjny Danilo Petroni (Mr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych