Objective The possibility to artificially induce and expand in vitro tissue-specific stem cells (SCs) is an important goal for regenerative medicine, to understand organ physiology, for in vitro modeling of human diseases and many other applications. Here we found that this goal can be achieved in the culture dish by transiently inducing expression of YAP or TAZ - nuclear effectors of the Hippo and biomechanical pathways - into primary/terminally differentiated cells of distinct tissue origins. Moreover, YAP/TAZ are essential endogenous factors that preserve ex-vivo naturally arising SCs of distinct tissues. In this grant, we aim to gain insights into YAP/TAZ molecular networks (upstream regulators and downstream targets) involved in somatic SC reprogramming and SC identity. Our studies will entail the identification of the genetic networks and epigenetic changes controlled by YAP/TAZ during cell de-differentiation and the re-acquisition of SC-traits in distinct cell types. We will also investigate upstream inputs establishing YAP/TAZ activity, with particular emphasis on biomechanical and cytoskeletal cues that represent overarching regulators of YAP/TAZ in tissues.For many tumors, it appears that acquisition of an immature, stem-like state is a prerequisite for tumor progression and an early step in oncogene-mediated transformation. YAP/TAZ activation is widespread in human tumors. However, a connection between YAP/TAZ and oncogene-induced cell plasticity has never been investigated. We will also pursue some intriguing preliminary results and investigate how oncogenes and chromatin remodelers may link to cell mechanics, and the plasticity of the differentiated and SC states by controlling YAP/TAZ.In sum, this research should advance our understanding of the cellular and molecular basis underpinning organ growth, tissue regeneration and tumor initiation. Fields of science medical and health sciencesbasic medicinepharmacology and pharmacydrug discoveryengineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringcontrol systemsmedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesbasic medicinephysiology Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-ADG-2014 - ERC Advanced Grant Call for proposal ERC-2014-ADG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Coordinator UNIVERSITA DEGLI STUDI DI PADOVA Net EU contribution € 2 239 422,75 Address Via 8 febbraio 2 35122 Padova Italy See on map Region Nord-Est Veneto Padova Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNIVERSITA DEGLI STUDI DI PADOVA Italy Net EU contribution € 2 239 422,75 Address Via 8 febbraio 2 35122 Padova See on map Region Nord-Est Veneto Padova Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 UNIVERSITA DEGLI STUDI DI MODENA E REGGIO EMILIA Italy Net EU contribution € 259 511,25 Address Via universita 4 41121 Modena See on map Region Nord-Est Emilia-Romagna Modena Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
