Graakjaer Jesper, Christensen Rikke, Kolvraa Steen, Serakinci Nedime
Department of Clinical Genetics, Vejle County Hospital, Vejle, Denmark.
BMC Mol Biol. 2007 Jun 13;8:49. doi: 10.1186/1471-2199-8-49.
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).
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.
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.
先前的研究表明，体细胞中的端粒并非随机分布于染色体末端。我们推测，端粒长度在染色体臂上的特异性差异（端粒长度模式）可能是被主动维持的。在本研究中，我们调查了干细胞中端粒长度模式的存在及维持情况。为此，我们研究了原代人骨髓间充质干细胞（hMSC）及其端粒酶永生化对应物（hMSC - telo1）在长期增殖过程以及照射后的端粒长度。使用荧光原位杂交（Q - FISH）测量端粒长度。
在原代hMSC以及hMSC - telo1中均发现存在端粒长度模式。该模式与先前在淋巴细胞和成纤维细胞中发现的模式相似。然后将细胞暴露于高剂量电离辐射。辐射导致染色体特异性端粒长度发生深刻变化，有效地破坏了端粒长度模式。辐射后长期培养后，发现端粒长度模式重新出现。然而，新的端粒长度模式与辐射前观察到的端粒长度模式不同。
我们的研究结果表明，间充质干细胞中确实存在端粒长度模式，并且该模式在被辐射破坏后不会主动重新建立。
