Mesenchymal stem cells with high telomerase expression do not actively restore their chromosome arm specific telomere length pattern after exposure to ionizing radiation

摘要

Background:Previous studies have demonstrated that telomeres in somatic cells are not randomly distributed at the end of the chromosomes.We hypothesize that these chromosome arm specific differences in telomere length(the telomere length pattern)may be actively maintained.In this study we investigate the existence and maintenance of the telomere length pattern in stem cells.For this aim we studied telomere length in primary human mesenchymal stem cells(hMSC)and their telomerase-immortalised counterpart(hMSC-telo1)during extended proliferation as well as after irradiation.Telomere lengths were measured using Fluorescence In Situ Hybridization(Q-FISH). Results:A telomere length pattern was found to exist in primary hMSC's as well as in hMSC-telo1. This pattern is similar to what was previously found in lymphocytes and fibroblasts.The cells were then exposed to a high dose of ionizing radiation.Irradiation caused profound changes in chromosome specific telomere lengths,effectively destroying the telomere length pattern. Following long term culturing after irradiation,a telomere length pattern was found to re-emerge. However,the new telomere length pattern did not resemble the telomere length pattern observed before irradiation. Conclusion:Our findings indicate that a telomere length pattern does exist in mesenchymal stem cells and that the pattern is not actively re-established after destruction by irradiation.