Radiation-induced bystander effect impaired human hematopoietic stem cells by oxidative DNA damage

With the immunodeficient mouse model coupled with TBI and coculture system, we found that the radiation-induced bystander effect also occurred to human hematopoietic cells. The long-term hematopoietic reconstitution of bystander human HSCs was significantly decreased, and the colony-forming ability of bystander human hematopoietic progenitor cells was reduced. Further study found that the bystander human hematopoietic cells initiated enhanced DNA damage responses (DDRs), cell cycle arrest and p53-dependent apoptosis, mainly due to oxidative stress. Moreover, some antioxidants could mitigate this bystander effect with different efficacies both in vitro and in vivo. Human CB-CD34+ cells were cocultured with 10 Gy IR or NR human BM cells using a transwell system. After 17 hours of coculture, the CD34+ cells in the insert were collected for RNA-seq.