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Publication : Telomerase is required to slow telomere shortening and extend replicative lifespan of HSCs during serial transplantation.

First Author  Allsopp RC Year  2003
Journal  Blood Volume  102
Issue  2 Pages  517-20
PubMed ID  12663456 Mgi Jnum  J:115695
Mgi Id  MGI:3692082 Doi  10.1182/blood-2002-07-2334
Citation  Allsopp RC, et al. (2003) Telomerase is required to slow telomere shortening and extend replicative lifespan of HSCs during serial transplantation. Blood 102(2):517-20
abstractText  Telomere shortening ultimately limits the replicative life span of cultured human somatic cells. Telomeres also shorten during replicative aging in vivo in hematopoietic cells, including early hematopoietic progenitors and hematopoietic stem cells (HSCs), 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 HSCs in vivo, we serially transplanted HSCs from wild-type and telomerase-deficient mice until exhaustion and monitored telomere length in HSCs during this process. Telomerase-deficient HSCs could be serially transplanted for only 2 rounds, whereas wild-type HSCs could be serially transplanted for at least 4 rounds. Furthermore, the rate of telomere shortening was increased approximately 2-fold during serial transplantation of telomerase-deficient HSCs. These findings suggest that one role for telomerase in the HSC is to partially counter the rate of telomere shortening during division of HSCs, thereby preventing premature loss of telomere function and providing added replicative capacity.
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