The Journal of Experimental Medicine
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Published online 16 April 2001.
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© The Rockefeller University Press, 0022-1007/2001/4/917/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 8, April 16, 2001 917-924

Original Article

Telomere Shortening Accompanies Increased Cell Cycle Activity during Serial Transplantation of Hematopoietic Stem Cells

Richard C. Allsoppa, Samuel Cheshiera, and Irving L. Weissmana

a Beckman Center, Pathology Department, Stanford University School of Medicine, Stanford University, Stanford, California 94305
Dept. of Pathology, Rm. B257, Stanford University School of Medicine, Stanford University, Stanford, CA.650-498-6255650-723-7389

irv{at}stanford.edu

Reactivation of telomerase and maintenance of telomere length can lead to the prevention of replicative senescence in some human somatic cells grown in vitro. To investigate whether telomere shortening might also play a role in the limitation of hematopoietic stem cell (HSC) division capacity in vivo, we analyzed telomere length during serial transplantation of murine HSCs. Southern blot analysis of telomere length in donor bone marrow cells revealed extensive shortening (~7 kb) after just two rounds of HSC transplantation. The number of cycling HSCs increased after transplantation and remained elevated for at least 4 mo, while the frequency of HSCs in the bone marrow was completely regenerated by 2 mo after transplantation. Direct analysis of telomeres in HSCs by fluorescent in situ hybridization during serial transplantation also revealed a reduction in telomere size. Together, these data show that telomeres shorten during division of HSCs in vivo, and are consistent with the hypothesis that telomere shortening may limit the replicative capacity of HSCs.

Key Words: hematopoietic stem cell • telomere • cell cycle • transplantation • mouse

Abbreviations used in this paper: FIGE, field inversion gel electrophoresis; FISH, fluorescent in situ hybridization; HSC, hematopoietic stem cell; PNA, peptide nucleic acid; TRF, terminal restriction fragment.

© 2001 The Rockefeller University Press


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