Telomerase Activity in Hematopoietic Cells Is Associated with Self-Renewal Potential

Abstract

It has been proposed that the biological clock underlying the limited division potential of eukaryotic cells is telomere length. We assayed telomerase activity in single cells of the hematopoietic and immune systems. We examined hematopoietic stem cells at four stages of differentiation, lineage-committed progenitors, and mature myeloid and lymphoid cells. The frequency of telomerase-expressing cells within each population was proportional to the frequency of cells thought to have self-renewal potential. Among bone marrow hematopoietic stem cells, 70% exhibited detectable telomerase activity. The telomerase-expressing somatic cells observed in this study are not thought to be immortal, and expression was not correlated with cell cycle distribution or differentiation state. This study demonstrates that the developmental characteristic most consistently associated with telomerase expression is self-renewal potential.

Telomere and telomerase in stem cells

“…In the haematopoietic system, telomerase-expressing cells are stem cells with self-renewal potential and their early descendants (Hiyama et al, 1995;Morrison et al, 1996). Age-dependent loss of telomeric DNA has been observed in both lymphocytes and neutrophils (Vaziri et al, 1993) as well as in other tissues (Hiyama et al, 1996;Wright and Shay, 2005).…”

“…Low levels of telomerase activity are readily detectable in HSCs and in some of their differentiated progeny including peripheral blood lymphocytes (Hiyama et al, 1995;Morrison et al, 1996). Nevertheless, the age-related loss of telomeric DNA in these cells suggests that telomerase activity in HSCs is insufficient to completely prevent telomere loss.…”

Expression of mouse telomerase reverse transcriptase during development, differentiation and proliferation

“…Lymphocyte activation upon antigen receptor stimulation or mitogen exposure leads to a strong induction of telomerase activity (Buchkovich and Greider, 1996;Bodnar et al, 1996;Morrison et al, 1996). To understand the basis for telomerase activation, mTERT and mTR expression were assayed in adult primary splenocytes cultured in the presence or absence of the T cell-speci®c mitogens phorbol myristic acid and ionomycin (PMA/I).…”

Human cord blood-derived primitive progenitors are enriched in CD34+c-kit− cells: correlation between long-term culture-initiating cells and telomerase expression

“…7,11 It was recently reported that human hematopoietic stem/progenitor cells and activated lymphocytes exhibit low levels of telomerase activity. [12][13][14] However, telomere shortening is observed in these cells, implying that the level of activity is insufficient to maintain stable telomere length and that the proliferative potential of these cells is limited. 5,13,15,16 Interestingly, it was reported that the developmental characteristic most consistently associated with telomerase expression is Correspondence: Y Sonoda, Department of Hygiene, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyoku, Kyoto 602, Japan; Fax: 075 251 5334 Received 28 October 1997; accepted 23 January 1998 self-renewal potential.…”

“…5,13,15,16 Interestingly, it was reported that the developmental characteristic most consistently associated with telomerase expression is Correspondence: Y Sonoda, Department of Hygiene, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyoku, Kyoto 602, Japan; Fax: 075 251 5334 Received 28 October 1997; accepted 23 January 1998 self-renewal potential. 14 Moreover, telomerase is up-regulated when cells enter the cell cycle. 12,13,16 These findings suggest that telomerase expression by hematopoietic stem/progenitor cells may correlate with their proliferative capacity.…”