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Dissociation of telomerase activity and telomere length maintenance in primitive human hematopoietic cells

机译:原始人类造血细胞中端粒酶活性的解离和端粒长度的维持

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Primitive human hematopoietic cells have low endogenous telomerase activity, yet telomeres are not maintained. In contrast, ectopic telomerase expression in fibroblasts and other cells leads to telomere length maintenance or elongation. It is unclear whether this disparity can be attributed to telomerase level or stems from fundamentally different telomere biology. Here, we show that telomerase overexpression does not prevent proliferation-associated telomere shortening in human hematopoietic cells, pointing to the existence of cell type-specific differences in telomere dynamics. Furthermore, we observed eventual stabilization of telomere length without detectable changes in telomerase activity during establishment of two leukemic cell lines from normal cord blood cells, indicating that additional cooperating events are required for telomere maintenance in immortalized human hematopoietic cells.
机译:人类原始造血细胞的内源性端粒酶活性低,但端粒却无法维持。相反,异位端粒酶在成纤维细胞和其他细胞中的表达导致端粒长度维持或延长。目前尚不清楚这种差异是否归因于端粒酶水平还是源于根本不同的端粒生物学。在这里,我们显示端粒酶的过表达不能阻止人类造血细胞中与增殖相关的端粒缩短,这表明端粒动力学中存在细胞类型特异性差异。此外,我们观察到最终端粒长度的稳定,而从正常脐带血细胞建立两个白血病细胞系的过程中,端粒酶活性没有可检测的变化,表明端粒维持永生化人类造血细胞还需要其他合作事件。

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