Role of telomerase on stem cells

干细胞具有三个突出的特征，即，端粒酶活性、无限增殖寿命和分化能力。端粒酶是一种酶，延长端粒序列在每个染色体末端，并允许细胞无限增殖。然而，一些零散的证据表明，端粒酶在维持干细胞的特征方面有额外的作用。用低浓度的过氧化氢连续处理诱导培养的人成纤维细胞的过早衰老，这在相同条件下在hTERT（人端粒酶基因）导入的成纤维细胞中未观察到。为了进一步了解端粒酶在延缓细胞早衰中的作用，本研究探讨了正常成纤维细胞与hTERT基因导入的成纤维细胞之间以及细胞衰老与早衰之间在细胞反应过程中信号转导过程的差异。根据人成纤维细胞衰老和过早衰老的进展，观察到p21的增强，这通过使用与报告基因缀合的p21启动子的报告基因测定得到证实。p21的增强是弱的，如果不是在所有，在hTERT引入的细胞绕过细胞衰老和早衰。我们无法找到hTERT表达的成纤维细胞绕过正常成纤维细胞停止增殖的早衰的原因。

Stem cells have three prominent characteristics, i.e., telomerase activity, unlimited proliferative life-span and ability to differentiate. Telomerase is an enzyme that elongates telomere sequences at each chromosome end and allows cells to proliferate indefinitely. Several lines of fragmental evidence, however, suggest that telomerase has additional roles for the maintenance of characteristics seen in stem cells. Premature senescence of cultured human fibroblasts was induced by continuous treatment with low concentrations of hydrogen peroxide, which was not observed in hTERT (human telomerase gene)-introduced fibroblasts under the same condition. To have some idea on the role of telomerase on the bypass of premature senescence, we searched for possible differences on signal transduction process during cell response between normal fibroblasts and hTERT-introduced fibroblasts and between cellular senescence and premature senescence. Enhancement of p21 was observed according to the progression of both cellular senescence and premature senescence of human fibroblasts, which was confirmed by reporter assay using p21 promoter conjugated by reporter gene. Enhancement of p21 was weak, if not at all, in hTERT-introduced cells which bypassed cellular senescence and premature senescence. We could not find the reason why hTERT-expressing fibroblasts bypassed premature senescence under which normal fibroblasts ceased proliferation.