Dissociation of telomerase activity and telomere length maintenance in primitive human hematopoietic cells.
Primitive human hematopoietic cells have low endogenous telomerase activity, yet telomeres are not maintained. In contrast, ectopic telomerase expression in fibroblasts and other cells leads to telomere length maintenance or elongation. It is unclear whether this disparity can be attributed to telomerase level or stems from fundamentally different telomere biology. Here, we show that telomerase overexpression does not prevent proliferation-associated telomere shortening in human hematopoietic cells, pointing to the existence of cell type-specific differences in telomere dynamics. Furthermore, we observed eventual stabilization of telomere length without detectable changes in telomerase activity during establishment of two leukemic cell lines from normal cord blood cells, indicating that additional cooperating events are required for telomere maintenance in immortalized human hematopoietic cells.
Wang
J C Y
JC
Department of Molecular and Medical Genetics, University of Toronto, Toronto, ON, Canada M5S 1A8.
Warner
J K
JK
Erdmann
N
N
Lansdorp
P M
PM
Harrington
L
L
Dick
J E
JE
D049109:Cell Proliferation; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D006367:HeLa Cells; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D006801:Humans; D016086:Lentivirus; D007938:Leukemia / Q000201:enzymology*; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000235:genetics*
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D019098:Telomerase; D016650:Fluorescein-5-isothiocyanate