| Description |
The migration of stem cells is a fundamental aspect of developmental biology that is directly relevant to regenerative medicine. Specifically, the signals that direct migratory stem cells to the necessary location could be used therapeutically to recruit transplanted or endogenous stem cells. Additionally, given the similarities between stem cell mobilization and cancer cell metastasis, the factors that induce mobilization may provide new anti-metastasis drug targets. We have learned much about the factors involved in adult stem cell migration from vertebrates; however, given the deep anatomical positions of most vertebrate stem cell populations, observing migration has proven difficult. Thus there remain many unanswered questions as to how stem cells migrate in response to both tissue homeostasis and regeneration that must be investigated in a simpler, more accessible system. We established the planaria, Schmidtea mediterranea as a model system for studying stem cell migration, which required the development of methodology for observing planarian stem cell movements in vivo. Therefore we evaluated tissue transplantation, partial irradiation, and cell transplantation for this purpose. After modification, we found tissue transplantation, the gold standard assay for stem cell function in other systems, and partial irradiation, an underused method for local stem cell ablation, to be effective methods for interrogating stem cell behaviors. Using these methods, we found that stem cell migration in planaria is a dynamic process. Although they constantly produce migratory progeny, planarian stem cells are nonmigratory during tissue homeostasis and require wounding to become mobile. Transplanted stem cells are capable of rescuing lethally irradiated hosts and migratory stem cells are collectively totipotent, similar to the rest of the stem cell population. We characterized the repopulation of the stem cell compartment during rescue and evaluated the movement of the transplanted stem cells in relationship to their progeny. Finally, multiple wounding events showed how stem cells integrate multiple wound signals during stem cell recruitment. The work presented here establishes planaria as a model system for studying stem cell migration and defines two useful assays for investigating stem cell function and behavior. This work will inform future studies aimed at discovering stem cell mobilization and recruitment factors. |
