Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes
Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes
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DOI：
10.1038/emboj.2011.26
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发表时间：
2011-03-16
期刊：
影响因子：
11.4
通讯作者：
Clevers, Hans
中科院分区：
文献类型：
--
作者：
Schepers, Arnout G.;Vries, Robert;Clevers, Hans
已经提出体细胞在它们可以经历的细胞分裂的数量上是有限的。这被认为是干细胞保持其完整性预防疾病的一种机制。然而，我们最近发现了肠隐窝干细胞，它们可以持续小鼠的一生，但每天都在分裂。我们现在用生物化学方法证明了原代分离的Lgr 5 + ve干细胞含有显著的端粒酶活性。端粒酶活性在这些干细胞的未分化后代中迅速降低，并且在分化的绒毛细胞中完全丧失。相反，染色体的不对称分离被认为是干细胞保护其基因组免受损害的机制。我们测定了Lgr 5 + ve干细胞在21.5 h的平均细胞周期长度，发现Lgr 5 + ve肠干细胞随机分离新合成的DNA链，与“不朽链”假说相反。The EMBO Journal（2011）30，1104-1109. doi：10.1038/daj.2011.26; 2011年2月4日在线发布
Somatic cells have been proposed to be limited in the number of cell divisions they can undergo. This is thought to be a mechanism by which stem cells retain their integrity preventing disease. However, we have recently discovered intestinal crypt stem cells that persist for the lifetime of a mouse, yet divide every day. We now demonstrate biochemically that primary isolated Lgr5 + ve stem cells contain significant telomerase activity. Telomerase activity rapidly decreases in the undifferentiated progeny of these stem cells and is entirely lost in differentiated villus cells. Conversely, asymmetric segregation of chromosomes has been proposed as a mechanism for stem cells to protect their genomes against damage. We determined the average cell cycle length of Lgr5 + ve stem cells at 21.5 h and find that Lgr5 + ve intestinal stem cells randomly segregate newly synthesized DNA strands, opposing the 'immortal strand' hypothesis. The EMBO Journal (2011) 30, 1104-1109. doi:10.1038/emboj.2011.26; Published online 4 February 2011