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Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age.
Open accessAbstract
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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“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]
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“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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Migliaccio, A. R., Migliaccio, G., Baldassarre, A. D., & Eddleman, K. A. (2002) · Bone Marrow Transplantation · doi:10.1038/sj.bmt.1703599 · Cited by 9
Metadata
- 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
- Publisher
- National Academy of Sciences
- Published
- 1994-10-11
- Volume
- 91
- Issue
- 21
- Pages
- 9857-9860
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- 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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