ROLE OF CHROMATIN REMODELING IN STEM CELL IDENTITY AND EPIGENETIC MEMORY SWITCH OCCURRING IN TISSUE REGENERATION

The cells in our body have all the same genes. However, our tissues contain many different cell types: neurons, liver cells, and others. Our cells differ because they have certain sets of genes that are "turned on", as well as others that are "turned off". Recently, scientists have identified "epigenetic factors" - distinct from the DNA sequence - that can switch genes on or off. Epigenetic factors regulate gene expression and when altered are responsible for pathological conditions. Indeed, many human genetic diseases are caused by epigenetic alterations. Unlike DNA sequence mutations, epigenetic changes are ideal target for gene therapy because they are by nature reversible. Stem cells are a special tissue, highly regulated at the epigenetic level, with the potential to generate any cell type. Stem cells regenerative potential makes them ideal reagents for treating many human genetic diseases. Remarkably, the stem cells of the model organism D.melanogaster are currently among the best-understood adult stem cells. Interestingly, during tissue regeneration after injury, well differentiated cells can also be converted into a new multipotent state with distinct epigenetic modifications. Interestingly, Drosophila imaginal discs, the precursors of the adult Fly appendages, are also a unique system for studying epigenetic plasticity occurring during regeneration. The possibility of manipulating the epigenetic pathways of pluripotent cells is of the highest interest for the applications in cell therapy and regenerative medicine and conceptually alternative to gene replacement. However, a mandatory step to get closer to potential epigenetic therapeutic strategies is to gain a full knowledge of the molecular events underlying epigenetic reprogramming. Thus, I propose to use a variety of biochemical and genetic approaches to unveil the epigenetic mechanisms involved in stem cell identity and cell fate switch using the model organism D.melanogaster.