Telomerase expression in the mammalian heart.
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.
Institute of Genetic Medicine, International Centre for Life, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK. gavin.richardson2@ncl.ac.uk
Gavin D
GD
Richardson
David
D
Breault
Grace
G
Horrocks
Suzanne
S
Cormack
Nicholas
N
Hole
W Andrew
WA
Owens
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009206:Myocardium / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D000950:Antigens, Ly; D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; C484469:Nkx2-5 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D019098:Telomerase; C509187:Tert protein, mouse