Telomere shortening accompanies increased cell cycle activity during serial transplantation of hematopoietic stem cells
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 viv...
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| Veröffentlicht in: | The Journal of experimental medicine 2001-04, Vol.193 (8), p.917-924 |
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| creator | Allsopp, R C Cheshier, S Weissman, I L |
| description | 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 ( approximately 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. |
| doi_str_mv | 10.1084/jem.193.8.917 |
| format | Article |
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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 ( approximately 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. 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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 ( approximately 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.</description><subject>Animals</subject><subject>Blotting, Southern</subject><subject>Bone Marrow Cells - cytology</subject><subject>Cell Cycle - physiology</subject><subject>Flow Cytometry</subject><subject>G2 Phase</subject><subject>Hematopoietic Stem Cell Transplantation - methods</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Hematopoietic Stem Cells - ultrastructure</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mitosis</subject><subject>Models, Biological</subject><subject>Original</subject><subject>S Phase</subject><subject>stem cell transplantation</subject><subject>Telomere - genetics</subject><subject>Telomere - ultrastructure</subject><subject>Time Factors</subject><subject>Transplantation, Isogeneic - physiology</subject><issn>0022-1007</issn><issn>1540-9538</issn><issn>1892-1007</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkbtvFDEQxi0EIkegpEWu6PYYP_ZsN0goCg8pEk2oLa93Nudo115sX9D99_jIiUdFNcX85pv55iPkNYMtAy3f3eOyZUZs9dYw9YRsWC-hM73QT8kGgPOOAagL8qKUewAmZb97Ti4YEyD7nm_Ij1uc04IZadmnXDGGeEed92lZXQxYaIg-oys4Uo_zTP3Rz9iAGh5CPdLxkE8DBXNwM63ZxbLOLlZXQ4o0TXSPi6tpTQFr8LRUXH7plJfk2eTmgq_O9ZJ8-3h9e_W5u_n66cvVh5vOSw21416Y3eDN2IOX_cBgUMIbPg7MGzZJzoRwzJlW5U4j7DgYNSiGivNeGj2JS_L-UXc9DAuOHmM7crZrDovLR5tcsP92Ytjbu_RgeXuqBN0E3p4Fcvp-wFLtEsrJgouYDsUqBb1QUvwXZEorwTVvYPcI-pxKyTj9voaBPWVqW6a2rbfatkwb_-ZvC3_oc4jiJ5ZVoHI</recordid><startdate>20010416</startdate><enddate>20010416</enddate><creator>Allsopp, R C</creator><creator>Cheshier, S</creator><creator>Weissman, I L</creator><general>The Rockefeller University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TM</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20010416</creationdate><title>Telomere shortening accompanies increased cell cycle activity during serial transplantation of hematopoietic stem cells</title><author>Allsopp, R C ; Cheshier, S ; Weissman, I L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c480t-2c396bc9d50c45b10b73c92db1c91f42133a1a9213468e062097b71e7225498f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Blotting, Southern</topic><topic>Bone Marrow Cells - cytology</topic><topic>Cell Cycle - physiology</topic><topic>Flow Cytometry</topic><topic>G2 Phase</topic><topic>Hematopoietic Stem Cell Transplantation - methods</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Hematopoietic Stem Cells - ultrastructure</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mitosis</topic><topic>Models, Biological</topic><topic>Original</topic><topic>S Phase</topic><topic>stem cell transplantation</topic><topic>Telomere - genetics</topic><topic>Telomere - ultrastructure</topic><topic>Time Factors</topic><topic>Transplantation, Isogeneic - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Allsopp, R C</creatorcontrib><creatorcontrib>Cheshier, S</creatorcontrib><creatorcontrib>Weissman, I L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of experimental medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Allsopp, R C</au><au>Cheshier, S</au><au>Weissman, I L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Telomere shortening accompanies increased cell cycle activity during serial transplantation of hematopoietic stem cells</atitle><jtitle>The Journal of experimental medicine</jtitle><addtitle>J Exp Med</addtitle><date>2001-04-16</date><risdate>2001</risdate><volume>193</volume><issue>8</issue><spage>917</spage><epage>924</epage><pages>917-924</pages><issn>0022-1007</issn><eissn>1540-9538</eissn><eissn>1892-1007</eissn><abstract>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 ( approximately 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.</abstract><cop>United States</cop><pub>The Rockefeller University Press</pub><pmid>11304552</pmid><doi>10.1084/jem.193.8.917</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of experimental medicine, 2001-04, Vol.193 (8), p.917-924 |
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| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Animals Blotting, Southern Bone Marrow Cells - cytology Cell Cycle - physiology Flow Cytometry G2 Phase Hematopoietic Stem Cell Transplantation - methods Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - ultrastructure Humans Mice Mice, Inbred C57BL Mitosis Models, Biological Original S Phase stem cell transplantation Telomere - genetics Telomere - ultrastructure Time Factors Transplantation, Isogeneic - physiology |
| title | Telomere shortening accompanies increased cell cycle activity during serial transplantation of hematopoietic stem cells |
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