Affiliation:
1. From the Terry Fox Laboratory, British Columbia Cancer Agency; the Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; and the Geron Corporation, Menlo Park, CA.
Abstract
Abstract
Telomerase is a ribonucleoprotein polymerase that synthesizes telomeric repeats onto the 3′ ends of eukaryotic chromosomes. Activation of telomerase may prevent telomeric shortening and correlates with cell immortality in the germline and certain tumor cells. Candidate hematopoietic stem cells (HSC) from adult bone marrow express low levels of telomerase, which is upregulated with proliferation and/or differentiation. To address this issue, we stimulated purified candidate HSC from human adult bone marrow with stem cell factor (SCF), interleukin-3 (IL-3), and Flt3-ligand (FL). After 5 days in culture, activity was detected in total cell extracts from IL-3–, SCF + FL–, SCF + IL-3–, FL + IL-3–, and SCF + IL-3 + FL–stimulated cultures, but not from cells cultured in SCF or FL alone. Within the CD34+fraction of the cultured cells, significant activity was found in the CD34+CD71+ fraction. In addition, PKH26 staining confirmed that detectable telomerase activity was present in dividing PKH26lo cells, whereas nondividing PKH26hi cells were telomerase negative. Because in these experiments no distinction could be made between cycling “candidate” stem cells that had retained or had lost self-renewal properties, fetal liver cells with a CD34+CD38− phenotype, highly enriched for cycling stem cells, were also examined and found to express readily detectable levels of telomerase activity. Given the replication-dependent loss of telomeric DNA in hematopoietic cells, these observations suggest that the observed telomerase activity in candidate stem cells is either expressed in a minor subset of stem cells or, more likely, is not sufficient to prevent telomere shortening.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
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