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Telomerase expression in the mammalian heart

Lookup NU author(s): Professor Gavin RichardsonORCiD, Dr Suzanne Cormack, Dr Andrew OwensORCiD

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Abstract

While the mammalian heart has low, but functionally significant, levels of telomerase expression, the cellular population responsible remains incompletely characterized. This study aimed to identify the cell types responsible for cardiac telomerase activity in neonatal, adult, and cryoinjured adult hearts using transgenic mice expressing green fluorescent protein (GFP), driven by the promoter for murine telomerase reverse transcriptase (mTert), which is a necessary and rate-limiting component of telomerase. A rare population of mTert-GFP-expressing cells was identified that possessed all detectable cardiac telomerase RNA and telomerase activity. It was heterogeneous and included cells coexpressing markers of cardiomyocytic, endothelial, and mesenchymal lineages, putative cardiac stem cell markers, and, interestingly, cardiomyocytes with a differentiated phenotype. Quantification using both flow cytometry and immunofluorescence identified a significant decline in mTert-GFP cells in adult animals compared to neonates (∼9- and ∼20-fold, respectively). Cardiac injury resulted in a ∼6.45-fold expansion of this population (P<0.005) compared with sham-operated controls. This study identifies the cells responsible for cardiac telomerase activity, demonstrates a significant diminution with age but a marked response to injury, and, given the relationship between telomerase activity and stem cell populations, suggests that they represent a potential target for further investigation of cardiac regenerative potential


Publication metadata

Author(s): Richardson GD, Breault D, Horrocks G, Cormack S, Hole H, Owens WA

Publication type: Article

Publication status: Published

Journal: FASEB Journal

Year: 2012

Volume: 26

Issue: 12

Pages: 4832-4840

Print publication date: 23/08/2012

Date deposited: 10/01/2013

ISSN (print): 0892-6638

ISSN (electronic): 1530-6860

Publisher: Federation of American Societies for Experimental Biology

URL: http://dx.doi.org/10.1096/fj.12-208843

DOI: 10.1096/fj.12-208843


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Funding

Funder referenceFunder name
Harvard Stem Cell Institute
PG/06/110/21521British Heart Foundation
R01 DK084056U.S. National Institutes of Health

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