Telomere Length in Subpopulations of Human Hematopoietic Cells

Ziffle, Jessica A.G. Van; Baerlocher, Gabriela M.; Lansdorp, Peter M.

doi:10.1634/stemcells.21-6-654

Cited by 49 publications

(37 citation statements)

References 30 publications

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“…From P3 to P9 there were Ϸ18 PDs with an average telomeric shortening of 130 bp per PD. This rate of telomere attrition is comparable with that of human bone marrow stem cells (9). Additionally, nearly 50% of the telomerase activity in hCSCs at P3-P4 was still present at P8-P9 (Fig.…”

Section: Resultssupporting

confidence: 74%

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Human cardiac stem cells

Bearzi

Rota

Hosoda

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

919

896

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The identification of cardiac progenitor cells in mammals raises the possibility that the human heart contains a population of stem cells capable of generating cardiomyocytes and coronary vessels. The characterization of human cardiac stem cells (hCSCs) would have important clinical implications for the management of the failing heart. We have established the conditions for the isolation and expansion of c-kit-positive hCSCs from small samples of myocardium. Additionally, we have tested whether these cells have the ability to form functionally competent human myocardium after infarction in immunocompromised animals. Here, we report the identification in vitro of a class of human c-kit-positive cardiac cells that possess the fundamental properties of stem cells: they are self-renewing, clonogenic, and multipotent. hCSCs differentiate predominantly into cardiomyocytes and, to a lesser extent, into smooth muscle cells and endothelial cells. When locally injected in the infarcted myocardium of immunodeficient mice and immunosuppressed rats, hCSCs generate a chimeric heart, which contains human myocardium composed of myocytes, coronary resistance arterioles, and capillaries. The human myocardium is structurally and functionally integrated with the rodent myocardium and contributes to the performance of the infarcted heart. Differentiated human cardiac cells possess only one set of human sex chromosomes excluding cell fusion. The lack of cell fusion was confirmed by the Cre-lox strategy. Thus, hCSCs can be isolated and expanded in vitro for subsequent autologous regeneration of dead myocardium in patients affected by heart failure of ischemic and nonischemic origin.generation of human myocardium ͉ progenitor cells ͉ stem cell niches

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Section: Resultssupporting

confidence: 74%

“…Critical telomere length associated with growth arrest and cellular senescence of hCSCs and human hematopoietic SCs varies from 2.0 to 1.5 kbp (3,9). The fraction of hCSCs with critical telomeric shortening increased from 1% at P3-P4 to 2% at P5-P6 and 5% at P8-P9.…”

Section: Resultsmentioning

confidence: 99%

Human cardiac stem cells

Bearzi

Rota

Hosoda

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

919

896

View full text Add to dashboard Cite

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“…The use of hematopoietic cells as a proxy for average individual telomere length is complicated by the variation in telomere length observed within leukocyte subsets (42), as well as quantifiable changes in subset populations observed to occur with aging (43). Selection of a specific leukocyte subset, for example lymphocytes, would eliminate cell-to-cell variation and theoretically provide a more constant measure, although there is evidence that whole-blood telomere length Cancer Epidemiology, Biomarkers & Preventioncorrelates well with the mononuclear population (44).…”

Section: Discussionmentioning

confidence: 99%

Longer Relative Telomere Length in Blood from Women with Sporadic and Familial Breast Cancer Compared with Healthy Controls

Gramatges

Telli

Balise

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Telomeres cap the ends of chromosomes and are composed of a series of noncoding hexamer repeats. Telomeres protect the integrity of DNA coding sequences and are integral to the maintenance of genomic stability. Previous studies have shown an association between shortened lymphocyte telomeres and increased risk for specific cancers. However, the association between telomere length and breast cancer risk is less clear. We examined the relative telomere length (RTL) in blood from women with no personal or family history of cancer (controls) compared with different populations of women with breast cancer and women at high genetic risk for developing breast cancer. RTL was determined as the telomere to single gene copy number ratio assessed by quantitative PCR. Breast cancer cases (low risk, n = 40; high risk, n = 62) had significantly longer RTL compared with unaffected controls (n = 50; mean RTL = 1.11 versus 0.84; P < 0.0001). The assessment of risk by RTL quartile showed an increased risk for breast cancer with each longer quartile, with the most significant risk observed in the longest quartile (odds ratio, 23.3; confidence interval, 4.4-122.3; P < 0.0003). Women without breast cancer but at high risk due to family history (n = 30) also showed longer telomeres than controls (mean RTL = 1.09 versus 0.84; P < 0.0001). Our analysis supports previous findings of longer RTL in breast cancer cases compared with controls, and is the first to observe longer RTL in women without breast cancer identified as high risk based on family history. Cancer Epidemiol Biomarkers Prev; 19(2); 605-13. ©2010 AACR.

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“…In line with this assumption, analysis of human HSC sub-populations revealed a decline in telomere length from immature CD34 þ 38À to more committed CD34 þ 38 þ cells. 58 As PB myeloid cells are characterized by a relatively short lifespan, one could hypothesize that, at any point of time, the telomere length in these cells reflects the telomere length of the HSC they are derived from. Indeed, comparative analysis revealed that telomere length in bone marrow aspirates as compared to peripheral blood leukocytes (PBLs) and mononuclear cells (MNCs) as well as in CD34 þ cells compared to PBSC harvests was shown to be closely correlated.…”

Section: Telomeres and Stem Cell Turnover In Normal Hematopoiesismentioning

confidence: 99%

Telomere length dynamics in normal hematopoiesis and in disease states characterized by increased stem cell turnover

Brümmendorf

Balabanov

2006

Leukemia

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Telomeres both reflect and limit the replicative lifespan of normal somatic cells. Immature sub-populations of human CD34 þ 38À hematopoietic stem cell (HSC) can be identified in vitro based on their growth kinetics and telomere length. Fluorescence in situ hybridization and flow cytometry (flow-FISH) has been used to characterize telomere length dynamics as a surrogate marker for HSC turnover in vivo. Investigations in normal steady-state hematopoiesis provided the basis for follow-up studies in model scenarios characterized by increased HSC turnover. Disorders with underlying malignant transformation of HSC (e.g., chronic myeloid leukemia (CML)) can be discriminated from disease states with increased HSC turnover rates secondary to depletion of the stem cell compartment, for example, as in defined bone marrow failure syndromes. In some of these model scenarios, the degree of telomere shortening can be correlated with disease duration, disease stage and severity as well as with response to diseasemodifying treatment strategies. Whether increased telomere shortening represents a causal link between HSC turnover, replicative senescence and/or the induction of genetic instability in acquired HSC disorders remains to be shown. However, data from congenital disorders, like dyskeratosis congenita (DKC), suggest that disturbed telomere maintenance may play a role for replicative exhaustion of the HSC pool in vivo.

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Telomere Length in Subpopulations of Human Hematopoietic Cells

Cited by 49 publications

References 30 publications

Human cardiac stem cells

Human cardiac stem cells

Longer Relative Telomere Length in Blood from Women with Sporadic and Familial Breast Cancer Compared with Healthy Controls

Telomere length dynamics in normal hematopoiesis and in disease states characterized by increased stem cell turnover

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