Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes

被引:165
作者
Schepers, Arnout G. [1 ,2 ]
Vries, Robert [1 ,2 ]
van den Born, Maaike [1 ,2 ]
van de Wetering, Marc [1 ,2 ]
Clevers, Hans [1 ,2 ]
机构
[1] Hubrecht Inst Dev Biol & Stem Cell Res, NL-3584 Utrecht, Netherlands
[2] Univ Med Ctr Utrecht, Utrecht, Netherlands
关键词
asymmetric segregation; immortal strand; Lgr5; stem cells; telomerase; REVERSE-TRANSCRIPTASE HTERT; MOUSE SMALL INTESTINE; DIFFERENTIATION; RENEWAL; TISSUES; PROTECT; ORIGIN; GENOME; GENE;
D O I
10.1038/emboj.2011.26
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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
引用
收藏
页码:1104 / 1109
页数:6
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