Nature:干细胞的衰老问题
2009-05-26 20:36:34   来源：   作者：  评论：0 点击：

血液、表皮和精液中的成年干细胞，通过非对称分裂维持高度分异的短寿命细胞群，在每次分裂时产生一个可以自我更新的干细胞和一个正在分异的细胞。打破更新与分异之间的平衡，会导致过度增殖（及形成肿瘤）或干细胞耗尽（及组织退化）。

Cheng等人利用果蝇雄性精细胞系作为模型，研究了组织衰老对非对称干细胞分裂的影响。正常情况下，生殖细胞中心体的取向精确地位于它们的小环境内，非对称干细胞分裂肯定可以进行。

实验表明，干细胞取向随年龄的变化会阻止或延迟细胞分裂，造成精子生成量的减少。

Nature 456 , 599-604 (4 December 2008) | doi :10.1038/nature07386 ; Received 1 April 2008; Accepted 1 September 2008; Published online 15 October 2008

Centrosome misorientation reduces stem cell division during ageing
Jun Cheng 1 , 5 , Nezaket Türkel 2 , 5 , 6 , Nahid Hemati 2 , 5 , Margaret T. Fuller 4 , Alan J. Hunt 1 & Yukiko M. Yama***a 2 , 3

Department of Biomedical Engineering, Center for Ultrafast Optical Science
Life Sciences Institute, Center for Stem Cell Biology,
Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA
Departments of Developmental Biology and Genetics, Stanford University, School of Medicine, Stanford, California 94305, USA
These authors contributed equally to this work.
Present address: Peter MacCallum Cancer Centre, Anatomy and Cell Biology Department, University of Melbourne, Melbourne, Victoria 3002, Australia.
Asymmetric division of adult stem cells generates one self-renewing stem cell and one differentiating cell, thereby maintaining tissue homeostasis. A decline in stem cell function has been proposed to contribute to tissue ageing, although the underlying mechanism is poorly understood. Here we show that changes in the stem cell orientation with respect to the niche during ageing contribute to the decline in spermatogenesis in the male germ line of Drosophila . Throughout the cell cycle, centrosomes in germline stem cells (GSCs) are oriented within their niche and this ensures asymmetric division. We found that GSCs containing misoriented centrosomes accumulate with age and that these GSCs are arrested or delayed in the cell cycle. The cell cycle arrest is transient, and GSCs appear to re-enter the cell cycle on correction of centrosome orientation. On the basis of these findings, we propose that cell cycle arrest associated with centrosome misorientation functions as a mechanism to ensure asymmetric stem cell division, and that the inability of stem cells to maintain correct orientation during ageing contributes to the decline in spermatogenesis. We also show that some of the misoriented GSCs probably originate from dedifferentiation of spermatogonia.