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Stem Cells, Vol. 14, No. 2, 239-248, March 1996
© 1996 AlphaMed Press

RAPID COMMUNICATION

Differential Expression of Telomerase Activity in Hematopoietic Progenitors from Adult Human Bone Marrow

Choy-Pik Chiua, Wieslawa Dragowskab, Nam Woo Kima, Homayoun Vaziria, Jane Yuib, Terry E. Thomasb, Calvin B. Harleya, Peter M. Lansdorpb

a Geron Corporation, Menlo Park, California, USA and
b The Terry Fox Laboratory, Vancouver, British Columbia, Canada

Key Words. Telomerase • Hematopoietic progenitors • TRAP assay • Primitive stem cells • Human bone marrow

Dr. Choy-Pik Chiu, Geron Corporation, 200 Constitution Drive, Menlo Park, CA 94025, USA or Dr. Peter Lansdorp, Terry Fox Laboratory, British Columbia Cancer Research Centre, 601 West 10th Avenue, Vancouver, B.C., Canada, V5Z 1L3.

The loss of telomeric DNA may serve as a mitotic clock which signals cell senescence and exit from cell cycle. Telomerase, an enzyme which synthesizes telomeric repeats de novo, is required to maintain telomere lengths. In humans, significant telomerase activity has been found in cells with essentially unlimited replicative potential such as reproductive cells in ovaries and testes, immortal cell lines and cancer tissues, but not in most normal somatic cells or tissues. We have now examined telomerase expression in subpopulations of hematopoietic cells from adult human bone marrow using a sensitive polymerase chain reaction-based telomeric repeat amplification protocol. Telomerase activity was found at low levels in the highly enriched primitive hematopoietic cells (CD34+CD71loCD45RAlo) and was increased transiently when these cells were cultured in the presence of a mixture of cytokines. In contrast, the early progenitors (CD34+CD71+) expressed telomerase activity at a higher level which was subsequently downregulated in response to cytokines. Telomerase activity remained low in the more mature CD34– cells upon exposure to cytokines. Taken together, our results suggest that telomerase is expressed at a basal level in all hematopoietic cell populations examined, is induced in a primitive subset of hematopoietic progenitor cells and is downregulated upon further proliferation and differentiation of these cells. We have previously observed telomere shortening in cytokine-stimulated primitive hematopoietic cells. The low and transient activation of telomerase activity described here thus appears insufficient to maintain telomere lengths in cultured hematopoietic cells.




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