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Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
Published on: April 13, 2015
A key role for telomerase reverse transcriptase unit in modulating human embryonic stem cell proliferation, cell
Chunbo Yang1, Stefan Przyborski, Michael J Cooke
1North East Institute for Stem Cell Research, Newcastle upon Tyne NE1 3BZ, United Kingdom.
Stem Cells (Dayton, Ohio)
|January 22, 2008
Summary
Telomerase reverse transcriptase (TERT) is crucial for human embryonic stem cell (ESC) pluripotency and self-renewal. Modulating TERT affects ESC proliferation, cell cycle, and differentiation potential, highlighting its role in maintaining stemness.
Area of Science:
- Stem cell biology
- Molecular genetics
- Cellular aging
Background:
- Human embryonic stem cells (hESC) possess self-renewal and differentiation capabilities.
- Telomerase activity, involving telomerase reverse transcriptase (TERT) and telomerase RNA (TR), is present in hESC but declines during differentiation.
- The precise role of telomerase in hESC self-renewal and differentiation remains to be fully elucidated.
Purpose of the Study:
- To investigate the function of telomerase reverse transcriptase (TERT) in maintaining human embryonic stem cell (hESC) pluripotency, self-renewal, and differentiation.
- To determine the impact of modulating TERT expression on hESC cell cycle regulation and telomere maintenance.
Main Methods:
- Modulation of telomerase reverse transcriptase (TERT) expression in human embryonic stem cells (hESC) via genetic manipulation.
- Assessment of hESC proliferation, colony-forming ability, and cell cycle phase distribution (G1, S).
- Analysis of gene expression (CYCLIN D1, CDC6), protein phosphorylation (RB), telomere length, peroxide levels, and in vitro/in vivo differentiation potential.
Main Results:
- Upregulation of TERT enhanced hESC proliferation, colony formation, and S-phase progression, correlating with increased CYCLIN D1, CDC6, and RB hyperphosphorylation.
- TERT overexpression in hESC led to maintained telomerase activity and reduced peroxide levels in differentiated progeny, suggesting enhanced oxidative stress resistance.
- TERT downregulation reduced hESC proliferation, increased G1 phase, and critically, impaired pluripotency and differentiation capacity, leading to loss of lineage potential.
Conclusions:
- Telomerase reverse transcriptase (TERT) plays a vital role in maintaining human embryonic stem cell (hESC) pluripotency.
- TERT is essential for regulating the hESC cell cycle and their capacity for in vitro differentiation.
- TERT modulation offers a potential strategy for controlling hESC fate and function.
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