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Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes
Author(s) -
Schepers Arnout G,
Vries Robert,
van den Born Maaike,
van de Wetering Marc,
Clevers Hans
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.26
Subject(s) - biology , stem cell , telomerase , lgr5 , microbiology and biotechnology , stem cell theory of aging , somatic cell , adult stem cell , stem cell marker , crypt , cancer stem cell , telomere , cellular differentiation , genetics , haematopoiesis , stem cell factor , dna , gene , endocrinology
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.