IDENTIFICATION OF GENES EXPRESSED IN DIFFERENTIATED CELLS INVOLVED IN STEM CELL REPOPULATION FOLLOWING LOW-DOSE XRAY TREATMENT IN PLANARIAN

A major challenge in stem cell research is the comprehension of the extrinsic control exerted in vivo by the niche. Despite the significant advances derived from the successful application of molecular, cellular, and genomic approaches in planarians, the nature of extrinsic signals regulating stem cell biology remains to be understood. With the aim to identify genes, preferentially enriched in differentiated cells, whose expression is involved in the regulation of stem cells, we took advantage from the stem cell repopulation process that follows low-dose X-ray treatment in planarians. Due to its awfulness, our idea is that this process might represent a context in which the release of signaling molecules by differentiated tissues is highly emphasized. We searched for differentially expressed tags in a DGE library obtained from low-dose treated animals sacrificed between 4 and 7 days after irradiation compared to a DGE library from control animals and we selected some upregulated genes on the basis of their fold change. Expression analysis of the selected genes in intact un-irradiated planarians by WISH experiments revealed that these genes were preferentially expressed in differentiated tissues such as the gut and in the cephalic ganglia and their expression strongly increased in low-dose irradiated animals respect to not-irradiated animals. Genetic silencing of some of them by RNA interference impaired the stem cell repopulation, suggesting a tight Extrinsic control of stem cell activity.