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首页> 外文期刊>Journal of Cellular Physiology >Duplicated chromosomal fragments stabilize shortened telomeres in normal human IMR-90 cells before transition to senescence
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Duplicated chromosomal fragments stabilize shortened telomeres in normal human IMR-90 cells before transition to senescence

机译：重复的染色体片段稳定在正常的人类端粒缩短imr - 90细胞前过渡到衰老

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摘要

To assess why during in vitro aging of fibroblasts the maintenance of chromosomal stability is effective or occasionally fails, a detailed cytogenetic analysis was performed in normal human IMR-90 fetal lung fibroblasts. The onset of senescence was inferred from proliferation activity, expression pattern of cell cycle regulating proteins, activity of β-galactosidase, and morphological features. Over the period of proliferation, a moderate increase of non-transmissible structural chromosomal aberrations was observed. In addition, using fluorescence in situ hybridization (mFISH and mBAND) techniques, we detected clonally expanding translocations in up to 70% of the analyzed metaphases, all involving one homolog of chromosome 9 as an acceptor. Notably, chromosomes are randomly involved as donor-chromosomes of the translocated terminal acentric fragments. These fragments result from duplication because the donor chromosomes are apparently unchanged. Interstitial telomeric signals were detectable at fusion sites, most likely belonging to chromosome 9. Quantitative fluorescence in situ hybridization (QFISH) detecting telomere sequences, followed by mFISH technique revealed that already in young cells the respective telomeres of one chromosome 9 were particularly short. For the first time, we have observed dysfunctional telomeres of one specific chromosome in normal human cells that have been stabilized by duplicated terminal sequences.
机译：评估在体外成纤维细胞的老化的原因染色体稳定性的维护有效或偶尔失败,详细细胞遗传学分析是在正常执行人类imr - 90胎儿肺成纤维细胞。衰老是推断从扩散细胞周期的活动,表达模式调节蛋白质、活性β牛乳糖,和形态学特征。增殖,适度增长non-transmissible结构染色体畸变是观察。荧光原位杂交(mFISH和mBAND)技术,我们发现无性繁殖系地扩大易位在高达70%的分析中期,所有涉及的相同器官之一9号染色体作为受体。是随机的donor-chromosomes涉及进行终端无着丝粒碎片。由于重复,因为碎片供体染色体显然是不变。间质端粒的信号被检测到融合网站,最有可能属于染色体9. 杂交(QFISH)检测端粒序列,其次是mFISH技术显示已经在各自的年轻细胞一条染色体的端粒9特别短。一个特定的功能失调的端粒染色体正常的人类细胞稳定的序列重复的终端。

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