Comparing transcriptional effects of radioprotection with dmPGE2 to that of other EP receptor agonists in both hematopoietic stem cells and bone marrow stromal cells

We report transcriptional analyses of individual and combined EP receptor stimulation in radioprotective administration of dmPGE2 and other EP receptor agonists with varying radioprotective capacities. We find that in both hematopoietic stem cells, and in BM stromal (non-hematopoietic) cells, dmPGE2 radioprotection is primarily mediated through EP4 stimulation, but full activity likely requires interactive stimulation of both EP4 and EP3. Mice (2 male and 2 female per treatment group for each cell type analyzed) were injected with either vehicle (Veh), EP3 agonist sulprostone (EP3), EP4 agonist rivenprost (EP4), both sulprostone and rivenprost (EP3+4), or misoprostol (Miso) 30 min prior to TBI at 853 cGy. Non-irradiated (NI) mice were concurrently injected with vehicle and sham-irradiated. Bone marrow was harvested 1 h post-TBI. For HSC samples, phenotypic HSCs (SLAM-LKS) were sorted by FACS prior to RNA extraction. For BM stroma, non-hematopoietic cells (CD45- Ter119-) were magnetically enriched prior to RNA extraction.