Abstract

The proliferative life-span of the stem cells that sustain hematopoiesis throughout life is not known. It has been proposed that the sequential loss of telomeric DNA from the ends of human chromosomes with each somatic cell division eventually reaches a critical point that triggers cellular senescence. We now show that candidate human stem cells with a CD34+CD38lo phenotype that were purified from adult bone marrow have shorter telomeres than cells from fetal liver or umbilical cord blood. We also found that cells produced in cytokine-supplemented cultures of purified precursor cells show a proliferation-associated loss of telomeric DNA. These findings strongly suggest that the proliferative potential of most, if not all, hematopoietic stem cells is limited and decreases with age, a concept that has widespread implications for models of normal and abnormal hematopoiesis as well as gene therapy.

Keywords

Stem cellHaematopoiesisBiologySomatic cellTelomereCD34Cell biologyAdult stem cellMitosisCell divisionStem cell theory of agingUmbilical cordCord bloodSenescenceHematopoietic stem cellImmunologyStem cell factorCellEmbryonic stem cellGeneticsGene

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Publication Info

Year
1994
Type
article
Volume
91
Issue
21
Pages
9857-9860
Citations
1142
Access
Closed

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Homayoun Vaziri, Wieslawa H. Dragowska, Richard Allsopp et al. (1994). Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age.. Proceedings of the National Academy of Sciences , 91 (21) , 9857-9860. https://doi.org/10.1073/pnas.91.21.9857

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DOI
10.1073/pnas.91.21.9857