Recent studies have identified and begun to characterize the roles of regenerative cellular plasticity in many organs. In Part I of our two-part Review, we discussed how cells reprogram following injury to the stomach and pancreas. We introduced the concept of a conserved cellular program, much like those governing division and death, which may allow mature cells to become regenerative. This program, paligenosis, is likely necessary to help organs repair the numerous injuries they face over the lifetime of an organism; however, we also postulated that rounds of paligenosis and redifferentiation may allow long-lived cells to accumulate and store oncogenic mutations, and could thereby contribute to tumorigenesis.We have termed the model wherein differentiated cells can store mutations and then unmask them upon cell cycle re-entry the 'cyclical hit' model of tumorigenesis. In the present Review (Part II), we discuss these concepts, and cell plasticity as a whole, in the skin and intestine. Although differentiation and repair are arguably more thoroughly studied in skin and intestine than in stomach and pancreas, it is less clear how mature skin and intestinal cells contribute to tumorigenesis. Moreover, we conclude our Review by discussing plasticity in all four organs, and look for conserved mechanisms and concepts that might help advance our knowledge of tumor formation and advance the development of therapies for treating or preventing cancers that might be shared across multiple organs.
- Stem cells