SENESCENCE OF IMMORTAL HUMAN FIBROBLASTS BY THE INTRODUCTION OF NORMAL HUMAN-CHROMOSOME-6
SENESCENCE OF IMMORTAL HUMAN FIBROBLASTS BY THE INTRODUCTION OF NORMAL HUMAN-CHROMOSOME-6
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DOI：
10.1073/pnas.91.12.5498
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发表时间：
1994-06-07
影响因子：
11.1
通讯作者：
ATHWAL, RS
中科院分区：
文献类型：
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作者：
SANDHU, AK;HUBBARD, K;ATHWAL, RS
在这些研究中，我们表明，正常的人类染色体6或6 q的引入可以抑制猴病毒40转化的人成纤维细胞（SV/HF）的永生表型。正常人成纤维细胞在培养中具有有限的寿命。SV/HF的永生克隆显示6号染色体的非随机重排。通过微细胞融合将存在于小鼠/人单染色体杂种中的单个人染色体引入SV/HF中，并通过选择先前整合到人染色体中的显性选择标记gpt来维持。带有6号染色体的SV/HF细胞克隆显示出有限的细胞分裂潜力和衰老细胞的形态特征。受抑制克隆的6号染色体丢失与永生克隆的再现相关。通过对供体染色体特异性DNA序列的分析，将衰老细胞中引入的6号染色体与亲本细胞的染色体区分开来。我们的研究结果进一步表明，在SV/HF永生表型的抑制是特定的染色体6。在SV/HF中，单独的人类染色体2、8或19的引入并不赋予细胞衰老。此外，将6号染色体导入人胶质母细胞瘤细胞不会导致衰老。基于这些结果，我们提出，至少有一个基因（SEN 6）的细胞衰老在人类成纤维细胞上的长臂6号染色体。
In these studies we show that introduction of a normal human chromosome 6 or 6q can suppress the immortal phenotype of simian virus 40-transformed human fibroblasts (SV/HF). Normal human fibroblasts have a limited life span in culture. Immortal clones of SV/HF displayed nonrandom rearrangements in chromosome 6. Single human chromosomes present in mouse/human monochromosomal hybrids were introduced into SV/HF via microcell fusion and maintained by selection for a dominant selectable marker gpt, previously integrated into the human chromosome. Clones of SV/HF cells bearing chromosome 6 displayed Limited potential for cell division and morphological characteristics of senescent cells. The loss of chromosome 6 from the suppressed clones correlated with the reappearance of immortal clones. Introduced chromosome 6 in the senescing cells was distinguished from those of parental cells by the analysis for DNA sequences specific for the donor chromosome. Our results further show that suppression of immortal phenotype in SV/HF is specific to chromosome 6. Introduction of individual human chromosomes 2, 8, or 19 did not impart cellular senescence in SV/HF. In addition, introduction of chromosome 6 into human glioblastoma cells did not lead to senescence. Based upon these results we propose that at least one of the genes (SEN6) for cellular senescence in human fibroblasts is present on the long arm of chromosome 6.