Ionizing radiation induces stem cell-like properties in a caspase-dependent manner in Drosophila

Abstract

Cancer treatments including ionizing radiation (IR) can induce cancer stem cell-like properties in non-stem cancer cells, an outcome that can interfere with therapeutic success. Yet, we understand little about what consequences of IR induces stem cell like properties and why some cancer cells show this response but not others. In previous studies, we identified a pool of epithelial cells in Drosophila larval wing discs that display IR-induced stem cell-like properties. These cells are resistant to killing by IR and, after radiation damage, change fate and translocate to regenerate parts of the disc that suffered more cell death. Here, we addressed how IR exposure results in the induction of stem cell-like behavior, and found a requirement for caspase activity. Unexpectedly, this requirement was mapped to the regenerative cells, suggesting a non-apoptotic role for caspases in the induction of stem cell-like behavior. We also performed a systematic probing of different regions of the wing disc by lineage tracing, in order to identify additional pools of cells with IR-induced regenerative properties. We identified two new populations of such cells. Unlike the original pool that helps regenerate the disc, the new pools of cells undergo abnormal regeneration to produce an ectopic, supernumerary wing disc. We also identified cells that lack the ability to display IR-induced regenerative behavior. Identification of different cell populations with different IR-induced regenerative potential will allow us to probe the molecular basis for these differences in the future.\n\nAUTHOR SUMMARYIonizing Radiation (IR), alone or in combination with other therapies, is used to treat an estimated half of all cancer patients. Yet, we understand little about why some tumors cells respond to treatment while others grow back (regenerate). We identified specific pools of cells within a Drosophila organ that are capable of regeneration after damage by IR. We also identified what it is about IR damage that allows these cells to regenerate. These results help us understand how cells regenerate after IR damage and will aid in designing better therapies that involve radiation.