生物学中有一种长期存在的认识：干细胞避免使用经典的细胞分裂方式，从而保持自身正确性，不断创造出健康的子细胞。不过，一项最新的研究却彻底颠覆了这种认识，哺乳动物造血干细胞的分裂方式与其他细胞并无二致，它们自身的染色体在子代中是随机分配的。相关论文8月29日在线发表于《自然》杂志。
干细胞能够源源不断地为各个组织补充新鲜细胞，从而保证机体的平稳运行。不过，在每一次的染色体复制过程中，干细胞都要冒着新染色体发生突变的风险。30多年来，科学家认为，干细胞一定是通过不对称分离染色体来避免变异发生，即新复制产生的染色体都用于构建子代细胞，而干细胞自身的染色体保持不变，稳定地作为正确的模板。这种理论也就是所谓的“不朽链假说”（immortal strand hypothesis）。
然而，这一理论并不牢靠。一些研究找到了支持该理论的证据，而还有一些针对果蝇和蠕虫的研究则表明，DNA确实是随机在亲代和子代间分配的，干细胞没有“刻意”保留。
为了弄清哺乳动物中的情况，美国密歇根大学的干细胞生物学家Sean Morrison和同事对造血干细胞进行了深入研究。最初10天，他们在小鼠的饮用水中加入5-溴2-脱氧尿嘧啶核苷（简称BrdU），它能选择性地掺入到处于细胞DNA合成期的单链DNA核苷酸序列中。随后，研究人员将饮用水换成清水，并在40天、70天和120天后分三批杀死并分析了一些小鼠。科学家认为，如果所有的BrdU都存在于干细胞中，那么就支持了“不朽链假说”；反之，BrdU分散开来则说明干细胞在复制过程中染色体是随机分配的。
事实表明，120天后，造血干细胞中的BrdU只剩下大约2%。进一步的实验也支持了这一结论。Morrison表示，“我们丝毫没有发现不对称染色体分离的证据。”
美国卡内基研究院的发育遗传学家Allan Spradling表示，“新的研究结果表明，至少在造血干细胞中，不对称分离理论是不成立的。这对相信该机制的人来说，是一个相当严重的打击。”（科学网 任霄鹏/编译） 原始出处: Natureadvance online publication 29 August 2007 | doi:10.1038/nature06115; Received 14 June 2007; Accepted 25 July 2007; Published online 29 August 2007 Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU Mark J. Kiel1, Shenghui He1, Rina Ashkenazi2, Sara N. Gentry2, Monica Teta3, Jake A. Kushner3, Trachette L. Jackson2 & Sean J. Morrison1 1. Howard Hughes Medical Institute, Life Sciences Institute, Department of Internal Medicine, and Centre for Stem Cell Biology, 2. Department of Mathematics, University of Michigan, Ann Arbor, Michigan 48109-2216, USA 3. Division of Endocrinology, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA Correspondence to: Sean J. Morrison1 Correspondence and requests for materials should be addressed to S.J.M. (Email: seanjm@umich.edu). Stem cells are proposed to segregate chromosomes asymmetrically during self-renewing divisions so that older ('immortal') DNA strands are retained in daughter stem cells whereas newly synthesized strands segregate to differentiating cells1, 2, 3, 4, 5, 6. Stem cells are also proposed to retain DNA labels, such as 5-bromo-2-deoxyuridine (BrdU), either because they segregate chromosomes asymmetrically or because they divide slowly5, 7, 8, 9. However, the purity of stem cells among BrdU-label-retaining cells has not been documented in any tissue, and the 'immortal strand hypothesis' has not been tested in a system with definitive stem cell markers. Here we tested these hypotheses in haematopoietic stem cells (HSCs), which can be highly purified using well characterized markers. We administered BrdU to newborn mice, mice treated with cyclophosphamide and granulocyte colony-stimulating factor, and normal adult mice for 4 to 10 days, followed by 70 days without BrdU. In each case, less than 6% of HSCs retained BrdU and less than 0.5% of all BrdU-retaining haematopoietic cells were HSCs, revealing that BrdU has poor specificity and poor sensitivity as an HSC marker. Sequential administration of 5-chloro-2-deoxyuridine and 5-iodo-2-deoxyuridine indicated that all HSCs segregate their chromosomes randomly. Division of individual HSCs in culture revealed no asymmetric segregation of the label. Thus, HSCs cannot be identified on the basis of BrdU-label retention and do not retain older DNA strands during division, indicating that these are not general properties of stem cells. 摘自《生物谷》 |
