Related Experiment Video
Updated: Dec 24, 2025
08:34
Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
Published on: April 13, 2015
10.6K
Telomere dysfunction cooperates with epigenetic alterations to impair murine embryonic stem cell fate commitment
Mélanie Criqui1, Aditi Qamra2, Tsz Wai Chu1
1Institut de Recherche en Immunologie et Cancérologie (IRIC), Département de biologie moléculaire, Faculté de Médecine, Université de Montréal, Montréal, Canada.
Elife
|April 17, 2020
Summary
Telomere dysfunction in stem cells alters chromatin and gene expression, impacting differentiation. Inhibiting epigenetic modifiers revealed an interdependent relationship between H3K27me3 and telomere integrity.
Area of Science:
- Epigenetics
- Stem Cell Biology
- Genomics
Background:
- The link between epigenetic changes and telomere dysfunction remains unclear.
- Previous work demonstrated telomere erosion causes differentiation instability in murine embryonic stem cells (mESCs) via DNA hypomethylation.
- Pluripotency factors are crucial for maintaining stem cell identity and differentiation potential.
Purpose of the Study:
- To investigate the role of telomerase reverse transcriptase (Tert) in epigenetic regulation during stem cell differentiation.
- To explore the impact of telomere dysfunction on chromatin accessibility and gene expression.
- To elucidate the relationship between H3K27 trimethylation and telomere integrity in stem cell lineage commitment.
Main Methods:
- Utilized telomerase reverse transcriptase null (Tert) mESCs to model telomere dysfunction.
- Analyzed genome-wide chromatin accessibility and gene expression changes during differentiation.
- Investigated the role of Polycomb Repressive Complex 2 (PRC2) and H3K27me3 demethylation using specific inhibitors.
- Assessed stem cell differentiation capacity and pluripotency gene expression.
Main Results:
- Tert mESCs exhibited genome-wide chromatin and gene expression alterations during differentiation.
- An increase in H3K27me3 globally and altered chromatin at the Pou5f1/Oct4 promoter were observed in Tert mESCs.
- Tert mESCs showed impaired differentiation and refractory response to differentiation cues.
- PRC2 inhibition worsened differentiation defects in Tert mESCs, while H3K27me3 demethylation inhibition partially rescued the phenotype.
Conclusions:
- Telomere dysfunction induces significant epigenetic alterations, including changes in H3K27me3, affecting stem cell differentiation.
- A novel interdependent relationship exists between H3K27me3 and telomere integrity in regulating stem cell lineage commitment.
- These findings have potential implications for understanding aging and cancer development.
Keywords:
cell differentiationchromosomesembryonic stem cellsepigeneticsgene expressionmousetelomerase reverse transcriptasetelomeresMore Related Videos
08:01Oct4GiP Reporter Assay to Study Genes that Regulate Mouse Embryonic Stem Cell Maintenance and Self-renewal
Published on: May 30, 2012
10.8K
11:53An Alternative Culture Method to Maintain Genomic Hypomethylation of Mouse Embryonic Stem Cells Using MEK Inhibitor PD0325901 and Vitamin C
Published on: June 1, 2018
6.9K
Related Concept Videos
02:15Replicative Cell Senescence
4.2K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
4.2K
02:54Nucleosome Remodeling
10.6K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
10.6K
01:37Epigenetic Regulation
3.6K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.6K
01:46Epigenetic Regulation
33.3K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.3K
01:14Maintenance of the ES Cell State
2.6K
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
2.6K
01:24Methods of Nuclear Reprogramming
2.1K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
2.1K