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

TY - JOUR

T1 - Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes

AU - Schepers, A.G.

AU - Vries, R.G.J.

AU - van den Born, M.M.W.

AU - van de Wetering, M.L.

AU - Clevers, H.

N1 - Reporting year: 2011

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

U2 - 10.1038/emboj.2011.26

DO - 10.1038/emboj.2011.26

M3 - Article

SN - 0261-4189

VL - 30

SP - 1104

EP - 1109

JO - EMBO Journal

JF - EMBO Journal

IS - 6

ER -