Telomerase Activity in Human HSCs

Stem cells from adult tissues, including skin (Harle-Bachor and Boukamp 1996, Yasumoto et al. 1996), gut (Kolquist et al. 1998), and blood (Broccoli et al. 1995, Chiu et al. 1996, Engelhardt et al. 1997, Morrison et al. 1996) in principle harbor low levels of telomerase activity. Among them, blood progenitor and stem cells show graduations of these basal telomerase levels (Chiu et al. 1996, Engelhardt et al. 1997, Hiyama et al. 1995, Yui et al. 1998). Thus, higher telomerase activity can be detected in bone marrow (BM) CD34+CD38+ committed progenitor cell fraction than in the CD34+CD38-/low fraction containing primitive hematopoietic progenitor cells (Hiyama et al. 1995). In turn, BM CD34+CD38- cells show lower telomerase activity compared to corresponding cells isolated from fetal liver (Yui et al. 1998). Initial basal telomerase levels in HSCs can be transiently upregulated in the course of in vitro cultures upon stimulation with cytokines including inter-leukin 3 (IL-3) (Engelhardt et al. 1997, Yui et al. 1998, Zimmermann et al. 2004). There is arguably a link between the cell cycle of HSCs and telomerase activity demonstrating an elevated activity in actively cycling cells and a downregulation upon differentiation and re-entry into G0, where most resting HSCs can be found

(Engelhardt et al. 1997, Zhu et al. 1996). Since repopulating HSCs represent only a minor fraction of the CD34+CD38- cells (Bhatia et al. 1997) and candidate human HSCs considered as nonobese diabetic severe combined immunodeficient (NOD/SCID) mice BM repopulation cells (SRCs) contain heterogeneous subpopulations with distinct engraftment and differentiation capacities (Glimm et al. 2001), the extent of telomerase activity in the rare SRCs is not known. A recent study using an hTERT-reporting adenoviral vector in cord blood (CB) CD34+ cells demonstrates an upregulated hTERT expression in proliferating short-term SRCs, which remains relatively high in committed colony-forming progenitor cells, but is downregulated in mature myeloid cells (Jaras et al. 2006). Nevertheless, a decreased self-renewal capacity of SRCs is found in this study as a consequence of hTERT upregulation.

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