Telomerase is required to slow telomere shortening and extend replicative lifespan of HSC during serial transplantation

Telomeres shortening ultimately limits the replicative lifespan of cultured human somatic cells. Telomeres also shorten during replicative aging in vivo in hematopoietic cells, including early hematopoietic progenitors and hematopoietic stem cells (HSC), from humans and mice, despite readily detectable levels of telomerase in these cells. To assess the relevance of telomerase to the long-term replicative capacity of HSC in vivo, we serially transplanted HSC from wild-type and telomerase-deficient mice until exhaustion and monitored telomere length in HSC during this process. Telomerase-deficient HSC could only be serially transplanted for 2 rounds, whereas wild-type HSC could be serially transplanted for at least 4 rounds. Furthermore, the rate of telomere shortening was increased ~2 fold during serial transplantation of telomerase-deficient HSC. These findings suggest that, one role for telomerase in the HSC is to partially counter the rate of telomere shortening during division of HSC, thereby preventing pre-mature loss of telomere function and providing added replicative capacity. For personal use only. on October 22, 2017. by guest www.bloodjournal.org From