Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands.
EMBO J. 2011 Mar 16;30(6):1104-9. doi: 10.1038/emboj.2011.26. Epub 2011 Feb 4.
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.
体细胞被认为其分裂次数是有限的。这种机制可以使干细胞保持完整性,预防疾病。然而,我们最近发现,肠道隐窝干细胞可以在老鼠的一生中持续存在,并且每天都在分裂。我们现在从生化角度证明,分离出来的原代 Lgr5+ve 干细胞含有大量端粒酶活性。端粒酶活性在这些干细胞的未分化后代中迅速下降,在分化的绒毛细胞中完全消失。相反,染色体的不对称分离被认为是干细胞保护基因组免受损伤的一种机制。我们确定 Lgr5+ve 干细胞的平均细胞周期长度为 21.5 小时,并且发现 Lgr5+ve 肠道干细胞随机分离新合成的 DNA 链,与“不朽链”假说相反。