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

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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

DOI 10.1073/pnas.91.21.9857PMC PMC44916

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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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Self-citation

Authors: Vaziri, H., Dragowska, W., Allsopp, R. C., Thomas, T. E., Harley, C. B., & Lansdorp, P. M.
Affiliations: Geron (United States) (US)
ORCID: Allsopp, R C
Lansdorp, P M
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1994-10-11
Volume: 91
Issue: 21
Pages: 9857-9860
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.91.21.9857
PMC: PMC44916
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: green
www.ncbi.nlm.nih.gov
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: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age.

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