Accumulation of short telomeres in human fibroblasts prior to replicative senescence
Accumulation of short telomeres in human fibroblasts prior to replicative senescence
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DOI：
10.1006/excr.2000.4823
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发表时间：
2000-04-10
影响因子：
3.7
通讯作者：
Landsdorp, PM
中科院分区：
文献类型：
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作者：
Martens, UM;Chavez, EA;Landsdorp, PM
端粒重复序列的丢失与人二倍体成纤维细胞（HDF）的体外复制性衰老有因果关系。为了研究端粒缩短信号细胞衰老的机制，我通过定量荧光原位杂交分析了多克隆和克隆HDF累积群体倍增时特定染色体末端的端粒长度。每个群体加倍时，单个端粒的端粒缩短率在50 ~ 150 bp之间，在衰老前积累了约1- 2kb的端粒重复序列。然而，观察到个别端粒测量为0.5 -1 kb的一些例外。在成纤维细胞克隆中，复制性衰老的开始与平均端粒荧光显著相关，但引人注目的是，与端粒长度最短的染色体无关。在培养的HDF的后期传代中短端粒的积累与基于端粒长度和衰老前端粒之间的有限重组的细胞选择是相容的。(C)北京大学出版社.
The loss of telomere repeats has been causally linked to in vitro replicative senescence of human diploid fibroblasts (HDFs). In order to study the mechanism(s) by which telomere shortening signals cell senescence, me analyzed the telomere length at specific chromosome ends at cumulative population doublings in polyclonal and clonal HDFs by quantitative fluorescence in situ hybridization. The rate of telomere shortening at individual telomeres varied between 50 and 150 bp per population doubling and short telomeres with an estimated 1-2 kb of telomere repeats accumulated prior to senescence, The average telomere length in specific chromosome ends was remarkably similar between clones. However, some exceptions with individual telomeres measuring 0,5-1 kb were observed, In the fibroblast clones, the onset of replicative senescence was significantly correlated with the mean telomere fluorescence but, strikingly, not with chromosomes with the shortest telomere length. The accumulation of short telomeres in late passages of cultured HDFs is compatible with selection of cells on the basis of telomere length and limited recombination between telomeres prior to senescence. (C) 2000 Academic Press.