Cloning and characterization of cellular senescence-associated genes in human fibroblasts by suppression subtractive hybridization
Cloning and characterization of cellular senescence-associated genes in human fibroblasts by suppression subtractive hybridization
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DOI：
10.1016/j.yexcr.2004.04.044
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发表时间：
2004-08-15
影响因子：
3.7
通讯作者：
Tong, TJ
中科院分区：
文献类型：
--
作者：
Guo, SZ;Zhang, ZY;Tong, TJ
细胞衰老标志着组织培养中正常细胞增殖寿命的结束，发生在细胞经历一定数量的群体倍增 (PDL) 后。它伴随着基因表达模式的改变。我们的实验室已将一种特定的人胚胎肺二倍体成纤维细胞系 2BS 作为衰老模型进行了研究。在这里，我们报告了一组从衰老和年轻 2BS 细胞的抑制消减 cDNA 文库中鉴定出的细胞衰老相关基因。它们包括三个新基因和六个先前鉴定的功能未知的基因。功能已知的基因属于多种功能途径，据报道这些途径会随着衰老的开始而改变。其中包括三种在衰老细胞中表达降低的前 mRNA 剪接因子。这表明 mRNA 剪接的调节在细胞衰老过程中发生了改变。此外，以前与细胞衰老无关的基因TOMI（Myb 1的靶标）的表达在衰老细胞中显示增加，并且我们证明反义TOMI基因在2BS细胞中的表达可以延缓衰老的进程。 (C) 2004 Elsevier Inc. 保留所有权利。
Cellular senescence marks the end of the proliferative life span of normal cells in tissue culture and occurs after cells have undergone a certain number of population doublings (PDLs). It is accompanied by alterations in the pattern of gene expression. A specific human embryonic lung diploid fibroblast cell line, 2BS, has been studied as a model of senescence in our laboratory. Here, we report a set of cellular senescence-associated genes identified from suppression subtractive cDNA libraries from senescent and young 2BS cells. They include three novel genes and six previously identified genes of unknown function. The genes whose functions are known belong to various functional pathways that have been reported to change with the onset of senescence. These include three pre-mRNA splicing factors with reduced expression in senescent cells.. indicating that the regulation of mRNA splicing is altered during cell senescence. In addition, the expression of the Gene TOMI (target of Myb 1), which has not previously been associated with cellular senescence, is shown to increase in senescent cells, and we demonstrate that the expression of antisense TOMI gene in 2BS cells can delay the progress of senescence. (C) 2004 Elsevier Inc. All rights reserved.