Cel The adult human organism contains heterogeneous reservoirs of pluripotent stem cells characterized by a diversified differentiation potential. Understanding their biology at a system level would advance our ability to selectively activate and control their differentiation potential. Aside from the basic implications this would represent a substantial progress in regenerative medicine by providing a rational framework for using small molecules to control cell trans-determination and reprogramming.Here we propose a combined experimental and modelling approach to assemble a predictive model of mesoderm stem cell differentiation. Different cell states are identified by a vector in the differentiation hyperspace, the coordinates of the vector being the activation levels of a large number of nodes of a logic model linking the cell signalling network to the transcription regulatory network.The premise of this proposal is that differentiation is equivalent to rewiring the cell regulatory network as a consequence of induced perturbation of the gene expression program. This process can be rationally controlled by perturbing specific nodes of the signalling network that in turn control transcription factor activation. We will develop this novel strategy using the mesoangioblast ex vivo differentiation system. Mesoangioblasts are one of the many different types of mesoderm stem/progenitor cells that exhibit myogenic potential. Ex vivo, they readily differentiate into striated muscle. However, under appropriate conditions they can also differentiate, into smooth muscle and adipocytes, albeit less efficiently. We will start by assembling, training and optimizing different predictive models for the undifferentiated mesoangioblast. Next by a combination of experiments and modelling approaches we will learn how, by perturbing the signalling models with different inhibitors and activators we can rewire the cell networks to induce trans-determination or reprogramming. Dziedzina nauki natural sciencesbiological sciencescell biologycell signalingmedical and health sciencesmedical biotechnologycells technologiesstem cells Program(-y) 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) Temat(-y) ERC-AG-LS2 - ERC Advanced Grant - Genetics, Genomics, Bioinformatics and Systems Biology Zaproszenie do składania wniosków ERC-2012-ADG_20120314 Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-AG - ERC Advanced Grant Instytucja przyjmująca UNIVERSITA DEGLI STUDI DI ROMA TOR VERGATA Wkład UE € 2 639 804,00 Adres VIA CRACOVIA 50 00133 Roma Włochy Zobacz na mapie Region Centro (IT) Lazio Roma Rodzaj działalności Higher or Secondary Education Establishments Kierownik naukowy Giovanni Cesareni (Prof.) Kontakt administracyjny Giuseppe Novelli (Prof.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych Beneficjenci (1) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko UNIVERSITA DEGLI STUDI DI ROMA TOR VERGATA Włochy Wkład UE € 2 639 804,00 Adres VIA CRACOVIA 50 00133 Roma Zobacz na mapie Region Centro (IT) Lazio Roma Rodzaj działalności Higher or Secondary Education Establishments Kierownik naukowy Giovanni Cesareni (Prof.) Kontakt administracyjny Giuseppe Novelli (Prof.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych