Article

Telomere length and proliferation potential of hematopoietic stem cells

Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, Canada.
Journal of Cell Science (Impact Factor: 5.43). 02/1995; 108 ( Pt 1)(1):1-6.
Source: PubMed

ABSTRACT

Hematopoietic stem cells have typically been defined as pluripotent cells with self-renewal capacity. Recent studies have shown striking differences in the mean length of telomeric repeat sequences at the end of chromosomes from human hematopoietic cells at different stages of development. The most likely explanation for these observations is that hematopoietic stem cells, like all other somatic cells studied to date, lose telomeric DNA upon each cell division. In this review, limitations in the replicative potential of hematopoietic stem cells are discussed in the context of possible clinical use of such cells for transplantation and gene therapy.

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    • "Evidence for the loss of telomeric DNA with proliferation of HSCs and ageing exists for more than two decades (Vaziri et al., 1994). For HSCs to be efficient in maintaining lifelong homeostasis, it was proposed that there might be a small sub-set of HSCs that remains quiescent or expresses telomerase at high levels (Lansdorp, 1995). Evidence suggests that both of the hypotheses might be working simultaneously for HSCs to possess LT-proliferation potential. "
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    Full-text · Article · Jan 2016 · Developmental Dynamics
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    • "During DNA replication, the linear ends of chromosomes are eroded at each cell division due to the end replication problem.1 Telomeres, the very ends of linear chromosomes, are predominantly composed of tandem repeats of short sequences; in vertebrates, the repeats consist of the TTAGGG hexanucleotide.2 Telomere lengths are also remarkably heterogeneous among individuals and vary according to the origin, age, and proliferative history of cells.3,4 Telomere length variations among individuals of the same age are, therefore, thought to be related to variations in ageing and longevity.5 "
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    ABSTRACT: Telomerase reverse transcriptase (TERT) is the protein component of telomerase and combined with an RNA molecule, telomerase RNA component, forms the telomerase enzyme responsible for telomere elongation. Telomerase is essential for maintaining telomere length from replicative attrition and thus contributes to the preservation of genome integrity. Although diverse mouse models have been developed and studied to prove the physiological roles of telomerase as a telomere- elongating enzyme, recent studies have revealed non-canonical TERT activities beyond telomeres. To gain insights into the physiological impact of extra-telomeric roles, this review revisits the strategies and phenotypes of telomerase mouse models in terms of the extra-telomeric functions of telomerase.
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    • ") were seeded in triplicate in 96-well plates (Nalgene Nunc) and cultured in serum depleted media containing various growth factors. The serum-deprived media is a modification of the serum-deprived media developed for growth of haematopoietic progenitors (Migliaccio et al., 1988; Lansdorp, 1995) and adapted for the growth of stromal progenitors (Gronthos and Simmons, 1995). Cells were incubated for 5 days with the following growth factors at 10–100 ng/ml: recombinant human BMP-2 (Cytolab/Peprotech, Rehovot, Israel), BMP-7 (Stryker Biotech, St Leonards, NSW, Australia), recombinant human EGF (Peprotech, Rocky Hill, NJ) recombinant human IGF-1 (Gropep, Thebarton, SA, Australia), recombinant human FGF-2 (Cytolab/Peprotech), recombinant human PDGF-BB (Peprotech), recombinant human TGF-b1 (Cytolab/Peprotech), recombinant human TGF-b3 (Cytolab/Peprotech), recombinant human TGF-a (Peprotech). "
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