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PMID: 7937905 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 21 ·1994-10-11 ·Pages 9857-60

Vaziri H, Dragowska W, Allsopp RC, Thomas TE, Harley CB, Lansdorp PM

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.

MeSH Terms
Adolescent Adult Aging/physiology Antigens, CD/analysis Bone Marrow/growth & development DNA/metabolism Fetal Blood Fetus Hematopoietic Stem Cells/cytology,physiology Humans Liver/cytology Middle Aged Mitosis Telomere/physiology,ultrastructure
Chemicals
Antigens, CD DNA
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Vaziri H
Geron Corporation, Menlo Park, CA 94025.
Dragowska W
Allsopp R C
Thomas T E
Harley C B
Lansdorp P M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.21.9857
Published
1994-10-11
Pages
9857-60
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC44916
Subset
IM
Grants
NIA NIH HHS · AG09383A · United States
NIAID NIH HHS · AI-29524 · United States
External Links
PubMed source DOI: 10.1073/pnas.91.21.9857 PMC Full Text View journal details
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