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Telomerase Activity in Candidate Stem Cells From Fetal Liver and
Adult Bone Marrow
Jane Yui,
Choy-Pik Chiu, and
Peter M. Lansdorp
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.
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.
Blood, Vol. 91 No. 9 (May 1), 1998:
pp. 3255-3262
© 1998 by The American Society of Hematology.
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