Normal somatic cells possess a finite life span owing to replicative senescence. Telomerase functions as a potential regulator of senescence in various cells. Expression level of human telomerase reverse transcriptase (hTERT) is correlated with telomerase activity and cellular immortalization. In this study, we investigated the effects of ectopic expression of hTERT on proliferation potential of chicken feather keratinocyte stem cells (FKSCs). We established FKSCs transduced with hTERT catalytic subunit fused with EGFP marker gene (hTERT-EGFP-FKSCs). hTERT-EGFP-FKSCs had the great potential of proliferation in vitro and expressed kerainocyte stem cell markers integrin beta1 and CD49c. Keratin 15 and keratin 19, as native FKSCs, were also detected in hTERT-EGFP-FKSCs. By the analysis of fluorescent RT-PCR, western blotting and TRAP assay, hTERT-EGFP-FKSCs were positive for telomerase activity, in comparison with native FKSCs showing no telomerase activity. We demonstrated that ectopic expression of hTERT could result in immortalization of FKSCs. Tumorigenecity of hTERT-EGFP-FKSCs were examined by soft agar assay and transplantation into NOD-SCID mice. Results showed that hTERT-EGFP-FKSCs sustained the cellular characteristics of native FKSCs and had no transforming activity. In vivo differentiation multipotentials of hTERT-EGFP-FKSCs were confirmed by transplantation into developing chicken embryos and in situ hybridization analysis. These data provide a novel framework for understanding human telomerase activity in different species and suggest a new insight for manipulating hTERT for therapeutic purposes in treating tissue injury and aging.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/jez.b.21302 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Characterizing SV40-hTERT Immortalized Human Lung Microvascular Endothelial Cells as Model System for Mechanical Stretch-Induced Lung Injury.
Int J Mol Sci
January 2025
Clinical Division of General Anaesthesia and Intensive Care Medicine, Department of Anesthesia, Genera Intensive Care and Pain Therapy, Medical University Vienna, 1090 Vienna, Austria.
Drug development for human disease relies on preclinical model systems such as human cell cultures and animal experiments before therapeutic treatments can ultimately be tested on humans in clinical studies. We here describe the generation of a novel human cell line (HLMVEC/SVTERT289) that we generated by transfection of microvascular endothelial cells from healthy donor lung tissue with the catalytic domain of telomerase and the SV40 large T/small t-antigen. These cells exhibited satisfactory growth characteristics and largely maintained their native characteristics, including morphology, cell surface marker expression, angiogenic potential and the protein composition of secreted extracellular vesicles.
View Article and Find Full Text PDFThe Plethora of RNA-Protein Interactions Model a Basis for RNA Therapies.
Genes (Basel)
January 2025
Department of Chemistry, The RNA Institute, University at Albany, SUNY, 1400 Washington Ave Extension, Albany, NY 12222, USA.
The notion of RNA-based therapeutics has gained wide attractions in both academic and commercial institutions. RNA is a polymer of nucleic acids that has been proven to be impressively versatile, dating to its hypothesized RNA World origins, evidenced by its enzymatic roles in facilitating DNA replication, mRNA decay, and protein synthesis. This is underscored through the activities of riboswitches, spliceosomes, ribosomes, and telomerases.
View Article and Find Full Text PDFA Review of Telomere Attrition in Cancer and Aging: Current Molecular Insights and Future Therapeutic Approaches.
Cancers (Basel)
January 2025
Department of Molecular Biosciences, University of South Florida, 4202 East Fowler Avenue, ISA2015, Tampa, FL 33620, USA.
Background/objectives: As cells divide, telomeres shorten through a phenomenon known as telomere attrition, which leads to unavoidable senescence of cells. Unprotected DNA exponentially increases the odds of mutations, which can evolve into premature aging disorders and tumorigenesis. There has been growing academic and clinical interest in exploring this duality and developing optimal therapeutic strategies to combat telomere attrition in aging and cellular immortality in cancer.
View Article and Find Full Text PDFsiRNA-mediated inhibition of hTERT enhances the effects of curcumin in promoting cell death in precursor-B acute lymphoblastic leukemia cells: an in silico and in vitro study.
Sci Rep
January 2025
Cellular and Molecular Research Center, Gerash University of Medical Sciences, Gerash, Iran.
This study investigates the interrelationship between human telomerase reverse transcriptase (hTERT) and ferroptosis in precursor-B (pre-B) acute lymphoblastic leukemia (ALL), specifically examining how hTERT modulation affects ferroptotic cell death pathways. Given that hTERT overexpression characterizes various cancer phenotypes and elevated telomerase activity is observed in early-stage and relapsed ALL, we investigated the molecular mechanisms linking hTERT regulation and ferroptosis in leukemia cells. The experimental design employed Nalm-6 and REH cell lines under three distinct conditions: curcumin treatment, hTERT siRNA knockdown, and their combination.
View Article and Find Full Text PDFPreferential Binding of a Long-Arm Porphyrin Ligand to Higher Order G-Quadruplex under Crowding Conditions.
J Phys Chem B
January 2025
College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.
Under conditions that are close to the real cellular environment, the human telomeric single-stranded overhang (∼200 nt) consisting of tens of TTAGGG repeats tends to form higher order structures of multiple G-quadruplex (G4) blocks. On account of the higher biological relevance of higher order G4 structures, ligand compounds binding to higher order G4 are significant for the drug design toward inhibiting telomerase activity. Here, we study the interaction between a cationic porphyrin derivative, 5,10,15,20-tetra{4-[2-(1-methyl-1-piperidinyl)propoxy]phenyl}porphyrin (T4), and a human telomeric G4-dimer (AG(TAG)) in the mimic intracellular molecularly crowded environment (PEG as a crowding agent) and K or Na solution (i.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!