Chiu C P, Dragowska W, Kim N W, Vaziri H, Yui J, Thomas T E, Harley C B, Lansdorp P M
Geron Corporation, Menlo Park, California, USA.
Stem Cells. 1996 Mar;14(2):239-48. doi: 10.1002/stem.140239.
The loss of telomeric DNA may serve as a mitotic clock which signals cell senescence and exit from cell cycle. Telomerase, and enzyme which synthesizes telomeric repeats de novo, is required to maintain telomere lengths. In humans, significant telomerase activity has been found in cells with essentially unlimited replicative potential such as reproductive cells in ovaries and testes, immortal cell lines and cancer tissues, but not in most normal somatic cells or tissues. We have now examined telomerase expression in subpopulations of hematopoietic cells from adult human bone marrow using a sensitive polymerase chain reaction-based telomeric repeat amplification protocol. Telomerase activity was found at low levels in the highly enriched primitive hematopoietic cells (CD34+CD71loCD45RAlo) and was increased transiently when these cells were cultured in the presence of a mixture of cytokines. In contrast, the early progenitors (CD34+CD71+) expressed telomerase activity at a higher level which was subsequently downregulated in response to cytokines. Telomerase activity remained low in the more mature CD34-cells upon exposure to cytokines. Taken together, our results suggest that telomerase is expressed at a basal level in all hematopoietic cell populations examined, is induced in a primitive subset of hematopoietic progenitor cells and is downregulated upon further proliferation and differentiation of these cells. We have previously observed telomere shortening in cytokine-stimulated primitive hematopoietic cells. The low and transient activation of telomerase activity described here thus appears insufficient to maintain telomere lengths in cultured hematopoietic cells.
端粒DNA的缺失可能充当有丝分裂时钟，发出细胞衰老和退出细胞周期的信号。端粒酶是一种能从头合成端粒重复序列的酶，对于维持端粒长度至关重要。在人类中，在具有基本无限复制潜能的细胞中发现了显著的端粒酶活性，如卵巢和睾丸中的生殖细胞、永生化细胞系和癌组织，但在大多数正常体细胞或组织中未发现。我们现在使用基于聚合酶链反应的敏感端粒重复序列扩增方案，检测了来自成人骨髓的造血细胞亚群中的端粒酶表达。在高度富集的原始造血细胞（CD34+CD71loCD45RAlo）中发现了低水平的端粒酶活性，当这些细胞在细胞因子混合物存在的情况下培养时，端粒酶活性会短暂增加。相比之下，早期祖细胞（CD34+CD71+）表达的端粒酶活性水平较高，随后在细胞因子的作用下被下调。暴露于细胞因子后，更成熟的CD34-细胞中的端粒酶活性仍然很低。综上所述，我们的结果表明，端粒酶在所检测的所有造血细胞群体中均以基础水平表达，在造血祖细胞的一个原始亚群中被诱导，并且在这些细胞进一步增殖和分化时被下调。我们之前观察到细胞因子刺激的原始造血细胞中端粒缩短。因此，这里描述的端粒酶活性的低水平和短暂激活似乎不足以维持培养的造血细胞中的端粒长度。
