This presentation will explore the re-mergence of cell plasticity as a way to understand how tissues repair themselves after injury. Before the hegemony of stem cell theory during the later decades of the twentieth century, it was mostly understood that cells could be plastic in adapting to injury. For example, even by 1900, it had been proposed that differentiated cells must have a program in cases like experimental partial hepatectomy, for switching their metabolic program from focusing energy on performing physiological functions to focusing energy on cell division. Our lab is beginning to identify the molecular mechanisms that dictate just such a shared program, which has been termed paligenosis. Paligenosis involves three sequential stages, each of which can be blocked to stop the entire program: autodegradation (with massive upregulation of lysosomes and autophagy), induction of progenitor gene expression, and then cell cycle re-entry. We discuss how there may be paligenosis-dedicated genes that regulate the energy hub mTORC1 to allow proper paligenosis, and we discuss how aberrant paligenosis may lead to a chronic precancerous (metaplastic) state and increase risk for cancer.
