RT Journal Article
SR Electronic
T1 Injury stimulates stem cells to resist radiation-induced apoptosis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 688168
DO 10.1101/688168
A1 Divya A Shiroor
A1 Tisha E Bohr
A1 Carolyn E Adler
YR 2019
UL http://biorxiv.org/content/early/2019/06/30/688168.abstract
AB Mechanical injuries cause widespread damage to tissues, fundamentally changing the physiological environment for subsequent repair. How these changes influence stem cells, which are central drivers of tissue repair and regeneration, is unknown. Planarian flatworms are highly capable regenerators, due to an abundant stem cell population that responds to wounding. Injury causes differentiated cells to die (Pellettieri et al., 2010) and stem cells to proliferate (Wenemoser and Reddien, 2010), but how these two events may be linked is unclear. To visualize stem cell dynamics after injury, we reduced their numbers by exposing animals to low doses of radiation (Wagner et al., 2011) and asked how the remaining stem cells respond to damage. We find that stem cells accumulate adjacent to injuries in large numbers, but only if injured within a defined window surrounding radiation. This accumulation occurs despite an absence of proliferation, indicating that stem cells are retained around the wound after radiation. Injury interferes with radiation-induced cell death, as stem cells from injured animals initiate apoptosis at significantly lower rates than uninjured controls. Injury is known to induce apoptosis in differentiated cells. By inducing rampant cell death throughout the body, we find that dying cells are sufficient to prolong survival of radiated stem cells. Together, our results suggest a model in which dying cells provide a protective signal to nearby stem cells, altering their susceptibility to radiation-induced apoptosis.