Telomere fluorescence measurements in granulocytes and T lymphocyte subsets point to a high turnover of hematopoietic stem cells and memory T cells in early childhood

被引:547
作者
Rufer, N
Brümmendorf, TH
Kolvraa, S
Bischoff, C
Christensen, K
Wadsworth, L
Schulzer, M
Lansdorp, PM
机构
[1] British Columbia Canc Res Ctr, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada
[2] Aarhus Univ, Inst Human Genet, DK-8000 Aarhus, Denmark
[3] Odense Univ, Sch Med, Inst Publ Hlth, DK-5000 Odense, Denmark
[4] British Columbia Childrens Hosp, Dept Pathol, Vancouver, BC V6H 3V4, Canada
[5] Univ British Columbia, Dept Med, Vancouver, BC V6T 2B5, Canada
[6] Univ British Columbia, Dept Stat, Vancouver, BC V6T 2B5, Canada
关键词
telomere length dynamics; telomere length inheritance; cellular turnover; immune senescence; stem cell self-renewal;
D O I
10.1084/jem.190.2.157
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
To study telomere length dynamics in hematopoietic cells with age, we analyzed the average length of telomere repeat sequences in diverse populations of nucleated blood cells. More than 500 individuals ranging in age from 0 to 90 yr, including 36 pairs of monozygous and dizygotic twins, were analyzed using quantitative fluorescence in situ hybridization and now cytometry. Granulocytes and naive T cells showed a parallel biphasic decline in telomere length with age that most likely reflected accumulated cell divisions in the common precursors of both cell types: hematopoietic stem cells. Telomere loss was very rapid in the first year, and continued for more than eight decades at a 30-fold lower rate. Memory T cells also showed an initial rapid decline in telomere length with age. However, in contrast to naive T cells, this decline continued for several years, and in older individuals lymphocytes typically had shorter telomeres than did granulocytes. Our findings point to a dramatic decline in stem cell turnover in early childhood and support the notion that cell divisions in hematopoietic stem cells and T cells result in loss of telomeric DNA.
引用
收藏
页码:157 / 167
页数:11
相关论文
共 50 条
  • [1] Changes of telomere length in children after hematopoietic stem cell transplantation
    Akiyama, M
    Hoshi, Y
    Sakurai, S
    Yamada, H
    Yamada, O
    Mizoguchi, H
    [J]. BONE MARROW TRANSPLANTATION, 1998, 21 (02) : 167 - 171
  • [2] TELOMERE LENGTH PREDICTS REPLICATIVE CAPACITY OF HUMAN FIBROBLASTS
    ALLSOPP, RC
    VAZIRI, H
    PATTERSON, C
    GOLDSTEIN, S
    YOUNGLAI, EV
    FUTCHER, AB
    GREIDER, CW
    HARLEY, CB
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (21) : 10114 - 10118
  • [3] EVIDENCE FOR A CRITICAL TELOMERE LENGTH IN SENESCENT HUMAN FIBROBLASTS
    ALLSOPP, RC
    HARLEY, CB
    [J]. EXPERIMENTAL CELL RESEARCH, 1995, 219 (01) : 130 - 136
  • [4] [Anonymous], APPL REGRESSION ANAL
  • [5] Asymmetric cell divisions sustain long-term hematopoiesis from single-sorted human fetal liver cells
    Brummendorf, TH
    Dragowska, W
    Zijlmans, JMJM
    Thornbury, G
    Lansdorp, PM
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (06) : 1117 - 1124
  • [6] The biology of replicative senescence
    Campisi, J
    [J]. EUROPEAN JOURNAL OF CANCER, 1997, 33 (05) : 703 - 709
  • [7] Differential expression of telomerase activity in hematopoietic progenitors from adult human bone marrow
    Chiu, CP
    Dragowska, W
    Kim, NW
    Vaziri, H
    Yui, J
    Thomas, TE
    Harley, CB
    Lansdorp, PM
    [J]. STEM CELLS, 1996, 14 (02) : 239 - 248
  • [8] Intrinsic and extrinsic control of hemopoietic stem cell numbers: Mapping of a stem cell gene
    deHaan, G
    VanZant, G
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (04) : 529 - 536
  • [9] Changes in thymic function with age and during the treatment of HIV infection
    Douek, DC
    McFarland, RD
    Keiser, PH
    Gage, EA
    Massey, JM
    Haynes, BF
    Polis, MA
    Haase, AT
    Feinberg, MB
    Sullivan, JL
    Jamieson, BD
    Zack, JA
    Picker, LJ
    Koup, RA
    [J]. NATURE, 1998, 396 (6712) : 690 - 695
  • [10] Replicative senescence of T cells: does the Hayflick Limit lead to immune exhaustion?
    Effros, RB
    Pawelec, G
    [J]. IMMUNOLOGY TODAY, 1997, 18 (09): : 450 - 454