THE POSTMITOTIC STATE OF TERMINALLY DIFFERENTIATED CELLS: UNDERLYING MECHANISMS AND OVERRIDING STRATEGIES

By definition, terminally differentiated cells are unable to proliferate. Organs such as the brain, the heart, and many endocrine glands are made almost exclusively of terminally differentiated cells. Thus, they are not able to repair their own damages by multiplying their constituent cells. On the basis of previous results obtained with Telethon financial support, we propose a strategy to induce terminally differentiated cells to proliferate. Such strategy relies on the suppression of proliferation-inhibitory molecules to be identified in the course of the proposed project. Inhibiting such molecules should make terminally differentiated cells able to proliferate under ordinary culture conditions. In addition, we propose to explore important mechanisms that determine the permanent arrest of proliferation in terminally differentiated cells. If successful, this project will open the way to innovative therapies of the nervous system, the heart, and other organs.