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猫血细胞端粒长度的纵向研究:对体内造血干细胞更新的影响

Longitudinal studies of telomere length in feline blood cells: implications for hematopoietic stem cell turnover in vivo.

作者信息

Brümmendorf Tim H, Mak Jennifer, Sabo Kathleen M, Baerlocher Gabriela M, Dietz Klaus, Abkowitz Janis L, Lansdorp Peter M

机构信息

Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, Canada.

出版信息

Exp Hematol. 2002 Oct;30(10):1147-52. doi: 10.1016/s0301-472x(02)00888-3.

DOI:10.1016/s0301-472x(02)00888-3
PMID:12384145
Abstract

OBJECTIVE

To address questions about stem cell turnover in relation to telomere length dynamics, we analyzed telomere length in serial blood samples from cats.

MATERIALS AND METHODS

Lymphocytes and granulocytes from two newborn kittens, a 2-year-old cat, a 10-year-old recipient of a double autologous stem cell transplant, and a 10-year-old control animal were analyzed by fluorescence in situ hybridization and flow cytometry at 2-week intervals over a 1-year period.

RESULTS

At study onset, long telomeres were found in granulocytes and lymphocytes from the two kittens (mean +/- SD: 70.2 +/- 3.1 and 72.5 +/- 3.1 telomere fluorescence units [TFU], respectively) compared with the 2-year-old cat (55.6 +/- 2.5 and 64.1 +/- 4.3 TFU, respectively) and the two adult animals (49.6 +/- 1.5 and 45.4 +/- 0.8 TFU, respectively). The rate of telomere shortening in both granulocytes and lymphocytes was most rapid in the kittens (slope: -16.7 +/- 1.4 and -15.6 +/- 0.2 TFU/year, respectively). As in humans, telomere shortening with age was more rapid in lymphocytes than in granulocytes. An average rate of telomere attrition of -0.52 +/- 0.03 TFU per cell division was calculated for cultured lymphocytes from the two kittens, approximately 5-fold higher than the rate observed in human cells.

CONCLUSIONS

The average telomere length in cats is 5- to 10-fold longer than in humans, but the rate of telomere shortening is much higher both in vivo and in vitro. These observations are compatible with similar stem cell kinetics in both species.

摘要

目的

为了解决与端粒长度动态变化相关的干细胞更新问题,我们分析了猫的系列血液样本中的端粒长度。

材料与方法

对两只新生小猫、一只2岁猫、一名接受双自体干细胞移植的10岁受者以及一只10岁对照动物的淋巴细胞和粒细胞,在1年时间内每隔2周通过荧光原位杂交和流式细胞术进行分析。

结果

在研究开始时,发现两只小猫的粒细胞和淋巴细胞中的端粒较长(平均±标准差:分别为70.2±3.1和72.5±3.1个端粒荧光单位[TFU]),相比之下,2岁猫的端粒长度分别为55.6±2.5和64.1±4.3 TFU,两只成年动物的端粒长度分别为49.6±1.5和45.4±0.8 TFU。小猫的粒细胞和淋巴细胞中端粒缩短速率最快(斜率:分别为-16.7±1.4和-15.6±0.2 TFU/年)。与人类一样,淋巴细胞中端粒随年龄缩短的速度比粒细胞更快。计算出两只小猫培养的淋巴细胞每个细胞分裂的端粒磨损平均速率为-0.52±0.03 TFU,约为人类细胞中观察到速率的5倍。

结论

猫的平均端粒长度比人类长5至10倍,但在体内和体外端粒缩短速率都要高得多。这些观察结果与两个物种中相似的干细胞动力学一致。

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