Cited by 1,132Telomeres, Telomerase, and SenescenceHematopoietic Stem Cell TransplantationMesenchymal stem cell research

Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age.

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Vaziri, H, Dragowska, W, Allsopp, R C, Thomas, T E, Harley, C B, Lansdorp, P M·1994·Proceedings of the National Academy of Sciences

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.

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Crossref · 10.1073/pnas.91.21.9857

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  • Telomeres shorten progressively in human HSCs from fetal liver, cord blood, or adult bone marrow, and this is linked to a strongly reduced proliferative potential.

    “telomeres progressively shorten in human HSCs isolated from fetal liver, cord blood, or adult bone marrow, which is associated with a strongly reduced proliferative potential.”

    From Aging of hematopoietic stem cells (2018) · cites this paper as [26]

  • In human somatic cells with high telomerase activity, such as haematopoietic stem cells, telomeres usually shorten with each division and with age.

    “Even in somatic human cells that are naturally enriched for telomerase activity, such as haematopoietic stem cells (HSCs), telomeres typically become shorter with each cell division and with age42,43.”

    From The telomere syndromes (2012) · cites this paper as [43]

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Authors
Vaziri, H., Dragowska, W., Allsopp, R. C., Thomas, T. E., Harley, C. B., & Lansdorp, P. M.
Affiliations
Geron (United States) (US)
Venue
Proceedings of the National Academy of Sciences
Published
1994-10-11
Volume
91
Issue
21
Pages
9857-9860
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2068409711
Cited by
1,132
References
41
Citations by year
2026: 7 · 2025: 12 · 2024: 5 · 2023: 11 · 2022: 22 · 2021: 14 · 2020: 31 · 2019: 22 · 2018: 20 · 2017: 24 · 2016: 20 · 2015: 29 · 2014: 36 · 2013: 40 · 2012: 39
FWCI
26.07
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute on Aging (AG09383A)
  • National Institute of Allergy and Infectious Diseases (AI 29524)
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
hematopoietic stem cells, telomere length, cellular senescence, stem cell aging, bone marrow, fetal liver, umbilical cord blood, hematopoiesis, gene therapy
MeSH terms
Adolescent, Adult, Aging, Bone Marrow, DNA, Fetal Blood, Fetus, Hematopoietic Stem Cells, Humans, Liver, Middle Aged, Mitosis, Antigens, CD, Telomere

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