Role of telomerase on stem cells

干细胞具有端粒酶活性、无限增殖寿命和分化能力三个突出特点。端粒酶是一种延长染色体末端端粒序列并使细胞无限增殖的酶。然而，一些零散的证据表明，端粒酶在维持干细胞特征方面具有额外的作用。低浓度过氧化氢连续处理可诱导培养的人成纤维细胞过早衰老，而在相同条件下，hTERT（人端粒酶基因）诱导的成纤维细胞未见此现象。为了进一步了解端粒酶在早衰中的作用，我们研究了正常成纤维细胞和引入htert的成纤维细胞在细胞应答过程中的信号转导过程以及细胞衰老和早衰之间可能存在的差异。用报告基因结合的p21启动子进行报告性实验，证实了p21在人成纤维细胞衰老和早衰过程中的增强作用。在引入htert的细胞中，p21的增强很弱，甚至没有增强，而htert绕过了细胞衰老和过早衰老。我们无法找到表达htert的成纤维细胞绕过正常成纤维细胞停止增殖的过早衰老的原因。

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.