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Date du début: 1 mars 2013, Date de fin: 28 févr. 2018 PROJET  TERMINÉ 

Recent progress on direct re-programming into functional neurons provides a new approach towards cell-based therapy for neurodegenerative disorders. The induced neurons (iNs) are a novel type of cell resulting from rapid and remarkable conversion of somatic cells into subtype-specific functional neurons. Importantly they are non-proliferating which make them interesting alternatives to induced pluripotent (iPS) cells as sources of patient specific neurons for exogenous cell replacement therapy and disease modeling.Another major advantage with direct conversion over iPS cells is that the reprogramming could be performed in vivo. While direct conversion has been successful in organs such as the pancreas, where exocrine cells can be directly converted into insulin producing cells by viral injections in vivo (Zhou et al., Nature, 2008), the method is yet to be explored in the brain. Once direct conversion of non-neuronal cells into subtype specific neurons directly in the brain is established, it provides a new strategy for cell based brain repair that do not depend on exogenous cells.The overall goal of this project is to provide proof-of-principle that induced neurogenesis is achievable in the adult brain through guided transcription factor reprogramming of non-neuronal cells, to determine which cells are best suited as cellular substrate for in vivo neural conversion, and to compare this approach with transplantation of converted fibroblasts.The ability to directly reprogram cell fate using defined combinations of transcription factors have already turned basic studies of stem cell differentiation and cell therapy into a new direction. Establishing this technique in vivo would be another paradigm-shifting finding that opens up for novel strategies for brain repair