Elsevier

Experimental Hematology

Volume 38, Issue 10, October 2010, Pages 854-859
Experimental Hematology

Clinical Investigation
Synchrony of telomere length among hematopoietic cells

https://doi.org/10.1016/j.exphem.2010.06.010Get rights and content

Objective

Little is known about the relationship of telomere length among leukocyte subsets and cells up the hematopoietic hierarchy. This information is relevant because telomere dynamics in granulocytes were postulated to mirror those of hematopoietic stem cells (HSCs).

Materials and Methods

In newborn umbilical cord blood (UCB), we examined the relationships of telomere length in hematopoietic progenitor cells (HPCs) (CD34+CD45) with those in T lymphocytes and granulocytes. In addition, we correlated telomere length in granulocytes with those in whole leukocyte samples of individuals ranging in age from birth to 100 years.

Results

In the UCB, we found strong correlations of telomere length in HPCs with telomere length in T lymphocytes (r ranging from 0.882 to 0.935; p ranging from 0.0038 to 0.0007) and in granulocytes (r = 0.930; p = 0.0072). At birth, strong correlations were also observed between telomere length in granulocytes and those in all leukocytes (r = 0.979; p = 0.0003). Throughout the human lifespan, the relationship between telomere length in granulocytes and that in all leukocytes was r > 0.980 and p < 0.0001.

Conclusions

Robust synchrony exists among leukocyte subsets throughout the human lifespan; individuals with relatively long (or short) telomeres in one leukocyte subset have long (or short) telomeres in other leukocyte subsets. Moreover, telomere length in leukocytes reflects its length in cells up the hematopoietic hierarchy, i.e., HPCs and, by inference, HSCs. Strong links have been found by many studies between leukocyte telomere length and a host of aging-related diseases. Our findings suggest, therefore, that these links might be traced to telomere dynamics in HSCs.

Section snippets

Subjects

UCB was obtained from the placenta of eight full-term normal newborns (six males, two females); one African American; six whites of Hispanic extraction; and one of mixed extraction.

UCB processing

UCB in citric acid/dextrose was obtained from The Southwest Blood and Tissue Center, San Antonio, TX. One milliliter of blood was spun down for 10 minutes at 1,500g in a cooled centrifuge and the Buffy coat layer was collected and saved at −80°C.

Ficoll separation of mononuclear cells

For Ficoll separation, blood was diluted 1:1 in RPMI-1640 medium

First phase

Figure 1A displays the relationships of telomere length in memory and naïve CD4+ and CD8+ T cells with CD34+ cells, which are primarily HPCs. There were strong correlations of telomere length in all T-cell subsets with telomere length in CD34+ cells. Using paired t-test, telomere length was 190 bp shorter in CD4+ memory cells than in CD4+ naïve cells (Fig. 2A) and 150 bp shorter in CD8+ memory than CD8+ naïve cells (Fig. 2B). In addition, there were strong correlations of telomere length

Discussion

The main findings of the study are as follows: at birth, telomere length in T cells and granulocytes are strongly correlated with telomere length in HPCs; in both newborns and adults, telomere length in granulocytes is highly correlated with LTL. These findings extend the concept of synchrony (equivalence) observed within tissues and organs of the newborn [20] and the fetus [22] to HPCs and leukocyte subsets in the newborn. They also show that adults with long (or short) LTL display long (or

Acknowledgments

Research reported in this article was supported by National Heart, Lung and Blood Institute (Bethesda, MD, USA) grants R01AG21593 and R01AG20132 and grants from the Canadian Institutes of Health Research (Ottawa, ON, Canada) (MOP38075 and GMH79042) and the National Cancer Institute of Canada (with support from the Terry Fox Run; Vancouver, BC, Canada).

Conflict of Interest Disclosure

There are no financial conflicts of interest for any of the authors.

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