Normal telomere erosion rates at the single cell level in Werner syndrome fibroblast cells
Normal telomere erosion rates at the single cell level in Werner syndrome fibroblast cells
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DOI：
10.1093/hmg/ddh159
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发表时间：
2004-07-15
影响因子：
3.5
通讯作者：
Kipling, D
中科院分区：
文献类型：
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作者：
Baird, DM;Davis, T;Kipling, D
本研究的目的是探讨在Werner综合征（WS）成纤维细胞中观察到的加速复制性衰老是否由于每次细胞分裂加速端粒丢失。通过单端粒长度分析（STELA），我们发现在WS批量培养中，端粒缩短的平均速率介于正常成纤维细胞（99 bp/群体加倍（PD））和正常成纤维细胞（355 bp/PD）的四倍之间。在培养的后期阶段，侵蚀速度最快的菌株的端粒侵蚀速率比在正常成纤维细胞中观察到的要慢，并且似乎与端粒长度分布的异质性减少有关。与大量培养相比，WS细胞克隆的端粒侵蚀率大大降低，端粒长度分布的差异也大大降低。克隆群体总体上缺乏长度异质性和正常的侵蚀率，这与简单的末端复制损失是WS细胞端粒侵蚀的主要原因是一致的。我们提出，在单细胞水平上，WS成纤维细胞的端粒动力学与正常成纤维细胞的端粒动力学没有显著差异，并且表明WS成纤维细胞中看到的增殖加速下降不是由于端粒加速侵蚀造成的。
The aim of this study was to investigate whether the accelerated replicative senescence seen in Werner syndrome (WS) fibroblasts is due to accelerated telomere loss per cell division. Using single telomere length analysis (STELA) we show that the mean rate of telomere shortening in WS bulk cultures ranges between that of normal fibroblasts [99 bp/population doubling (PD)] and four times that of normal (355 bp/PD). The telomere erosion rate in the fastest eroding strain slows in the later stages of culture to that observed in normal fibroblasts, and appears to be correlated with a reduction in the heterogeneity of the telomere-length distributions. Telomere erosion rates in clones of WS cells are much reduced compared with bulk cultures, as are the variances of the telomere-length distributions. The overall lack of length heterogeneity and the normal erosion rates of the clonal populations are consistent with simple end-replication losses as the major contributor to telomere erosion in WS cells. We propose that telomere dynamics at the single cell level in WS fibroblasts are not significantly different from those in normal fibroblasts, and suggest that the accelerated replicative decline seen in WS fibroblasts does not result from accelerated telomere erosion.