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.
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16 April 2001
Article|
April 09 2001
Telomere Shortening Accompanies Increased Cell Cycle Activity during Serial Transplantation of Hematopoietic Stem Cells
Richard C. Allsopp,
Richard C. Allsopp
aBeckman Center, Pathology Department, Stanford University School of Medicine, Stanford University, Stanford, California 94305
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Samuel Cheshier,
Samuel Cheshier
aBeckman Center, Pathology Department, Stanford University School of Medicine, Stanford University, Stanford, California 94305
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Irving L. Weissman
Irving L. Weissman
aBeckman Center, Pathology Department, Stanford University School of Medicine, Stanford University, Stanford, California 94305
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Richard C. Allsopp
aBeckman Center, Pathology Department, Stanford University School of Medicine, Stanford University, Stanford, California 94305
Samuel Cheshier
aBeckman Center, Pathology Department, Stanford University School of Medicine, Stanford University, Stanford, California 94305
Irving L. Weissman
aBeckman Center, Pathology Department, Stanford University School of Medicine, Stanford University, Stanford, California 94305
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.
Received:
November 27 2000
Revision Requested:
February 15 2001
Accepted:
February 20 2001
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2001 The Rockefeller University Press
2001
The Rockefeller University Press
J Exp Med (2001) 193 (8): 917–924.
Article history
Received:
November 27 2000
Revision Requested:
February 15 2001
Accepted:
February 20 2001
Citation
Richard C. Allsopp, Samuel Cheshier, Irving L. Weissman; Telomere Shortening Accompanies Increased Cell Cycle Activity during Serial Transplantation of Hematopoietic Stem Cells. J Exp Med 16 April 2001; 193 (8): 917–924. doi: https://doi.org/10.1084/jem.193.8.917
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