Injury stimulates stem cells to resist radiation-induced apoptosis

Abstract

Stem cells are continuously exposed to multiple stresses including radiation and tissue injury. Because stem cells are central drivers of tissue repair and regeneration, it is essential to understand how their behavior is influenced by these stressors. Planarians have an abundant population of stem cells that are rapidly eliminated after radiation exposure via apoptosis. Low doses of radiation eliminate the majority of these stem cells, allowing a few to remain [1]. Here, we combine radiation with injury to define how surviving stem cells respond to tissue damage. We find that injuries induce stem cells to persist, but only if injured within a defined window of time surrounding radiation, and only immediately adjacent to the wound. Stem cells persist for several days without any proliferation. Instead, they are retained near the wound due to suppression of apoptosis, which we quantify in stem cells by combining FACS with Annexin V staining. Tissue injury is known to induce apoptosis in differentiated cells [2], and we hypothesize that these dying cells confer apoptosis resistance onto nearby stem cells. Indeed, pharmacological induction of cell death with cycloheximide is sufficient to prolong survival of radiated stem cells even in the absence of injury. Together, our results suggest a model in which dying cells provide a transient protective signal to nearby stem cells, altering their susceptibility to radiation-induced apoptosis.