Senescence-specific gene expression fingerprints

Abstract: Replicative senescence is the state of irreversible proliferative arrest that occurs as a concomitant of progressive telomere shortening. By using cDNA microarrays and the gabriel system of computer programs to apply domain-specific and procedural knowledge for data analysis, we investigated global changes in gene transcription occurring during replicative senescence in human fibroblasts and mammary epithelial cells (HMECs). Here we report the identification of transcriptional "fingerprints" unique to senescence, the finding that gene expression perturbations during senescence differ greatly in fibroblasts and HMECs, and the discovery that despite the disparate nature of the chromosomal loci affected by senescence in fibroblasts and HMECs, the up-regulated loci in both types of cells show physical clustering. This clustering, which contrasts with the random distribution of genes down-regulated during senescence or up-regulated during reversible proliferative arrest (i.e., quiescence), supports the view that replicative senescence is associated with alteration of chromatin structure. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series摘要：复制性衰老（Replicative Senescence）是伴随端粒进行性缩短而发生的不可逆增殖停滞状态。本研究借助cDNA微阵列（cDNA microarray）与加布里埃尔计算机程序系统（gabriel system of computer programs），将领域专属知识与流程化分析知识应用于数据分析，以此探究人类成纤维细胞与乳腺上皮细胞（HMECs）在复制性衰老过程中的全局基因转录变化。本研究鉴定出衰老特异性的转录“指纹”，发现成纤维细胞与乳腺上皮细胞在衰老过程中的基因表达扰动差异显著；同时证实，尽管两类细胞中受衰老影响的染色体位点性质迥异，但二者的上调基因位点均呈现物理聚集现象。该聚集现象与衰老过程中下调基因或可逆增殖停滞（即静息状态，quiescence）过程中上调基因的随机分布形成鲜明对比，支持了复制性衰老与染色质结构改变相关的学术观点。本超系列（SuperSeries）由下述子系列（SubSeries）组成，请参阅各独立系列。