Differential transcriptional responses of stem and differentiated non-stem cells to ionizing radiation exposure.. Mus musculus

Cells differ in their response to ionizing radiation (IR) depending on the cell type, proliferation rate and cell cycle stage. Normal stem cells exhibit a radiosensitive phenotype contributing to normal tissue injury following radiotherapy, whereas differentiated cells are comparably resistant to IR-induced programmed cell death. An improved understanding of differential radiation responses in varying cellular contexts and their mechanistic distinction is imperative for efficient treatment of malignancies by radiotherapy. Low dose IR induced apoptosis is exclusively confined to the normal stem cells in multiple stem cell niches in vivo and the radiation hypersensitivity is recapitulated in primary stem cell culture models of embryonic and neuronal stem cells contrasting their isogenic differentiated non-stem radioresistant progeny. Transcriptional profiles of primary, early passage, mouse embryonic stem cells and isogenic differentiated non-stem cells were compared to discover genes that are selectively induced in stem cells, but not in differentiated cells; to characterize potential molecular regulators of stem cell radiosensitivity. These molecular insights may contribute to the development of therapeutics that minimize normal tissue injury. Overall design: Mouse embryonic Stem Cells (ES) and isogenic differentiated non-stem cells (ED) were irradiated with 10Gy. Total RNA samples for expression profiling was obtained from ES & ED cells after 15minutes (ESRE and EDRE) and 4 hours (ESRL and EDRL) post IR. Irradiated sample was analyzed in triplicates along with unirradiated ES and ED control cells.