AUG 21, 2019 11:09 AM PDT

Insights Into the Mechanisms Controlling Pluripotency

WRITTEN BY: Carmen Leitch

To carry out all the functions required for the maintenance of life, many types of specialized cells have to serve specific purposes, like heart cells, brain cells, nerve cells, etc. Pluripotent stem cells have incredible potential; they are self-renewing and can become any type of cell in the body. Scientists have long wanted to harness this power; pluripotent stem cells could revolutionize regenerative medicine, help create organs for transplant, or advance disease modeling in research. Scientists are still trying to understand pluripotency and the gene expression that gives cells that power. Now researchers led by Maria Blasco at the Spanish National Cancer Research Centre (CNIO) has revealed new characteristics of pluripotent cells.

Image credit: Public Domain Images

Reporting in eLife, the researchers have uncovered a new link between pluripotency and telomeres, the protective caps that sit on the ends of chromosomes. Telomeres have to be maintained constantly and were once thought to not encode for any genes. But research revealed that they generate long, non-coding RNA molecules called TERRA.

The CNIO scientists found that TERRAs can influence pluripotent genes through the action of Polycomb proteins, which can modify gene expression by adding biochemical tags to genes. TERRAs are controlled by another protein only found in telomeres called TRF1, which is a portion of a complex called shelterin, which protects telomeres.

Pluripotent cells can be engineered in the lab by modifying gene expression in adult skin cells. But in this study, the researchers found that when TRF1 was inactive in a cell, they could not trigger pluripotency. "We could not understand how a gene that deals with telomere maintenance has such a profound effect on a global process like pluripotency," noted Maria Blasco, Head of the Telomeres and Telomerase Group at CNIO.

To learn more, they searched for expression changes in genes after stopping TRF1 activity. They found many shifts, and more than 80 percent of those expression changes were connected to pluripotency. "We saw that TRF1 had an enormous, but very organized, effect," explains Blasco. Many of the genes they identified were controlled by Polycomb.

Image: In normal iPS cells (induced pluripotent stem cells) TRF1 expression is high, and the Polycomb (PRC2) complex (EDD, EZH2, and Suz12) is bound weakly to the genome, so pluripotency genes are expressed. After TRF1 depletion, TERRA expression increases, resulting in PRC2 recruitment to pluripotency and differentiation genes, and establishment of the K27me3 epigenetic mark, altering gene expression / Credit: CNIO

The scientists knew that Polycomb was related to telomere structure along with TERRA. The team looked for interactions between TERRA and the genome, and fund that TERRA targets genes that are also influenced by Polycomb. TERRA seemed to be the link between pluripotency and TRF1.

TRF1 has a cascading impact on gene expression in pluripotent cells using epigenetic changes.

Rosa Marión, the first author of the study, explained that "these findings tell us that TRF1 is essential for reprogramming specialized cells and for maintaining pluripotency."

Learn more about stem cells from the videos.


Sources: AAAS/Eurekalert! via CNIO, eLife

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
SEP 01, 2020
Genetics & Genomics
Women's Genes May Help Protect Against the Worst Alzheimer's Cases
SEP 01, 2020
Women's Genes May Help Protect Against the Worst Alzheimer's Cases
Women tend to get Alzheimer's more than men, but the female genome gives them some protection from the worst aspects of ...
OCT 04, 2020
Genetics & Genomics
The Intriguing Genome of Mitochondria
OCT 04, 2020
The Intriguing Genome of Mitochondria
Our cells carry special structures called organelles, with each different organelle performing various specialized, crit ...
OCT 11, 2020
Genetics & Genomics
Using Terahertz Waves to Control Gene Expression
OCT 11, 2020
Using Terahertz Waves to Control Gene Expression
Terahertz waves sit in the far infrared/microwave portion of the electromagnetic spectrum, and can be generated by power ...
OCT 19, 2020
Plants & Animals
Genetically Engineered Foods Could Alleviate Nutritional Deficiencies
OCT 19, 2020
Genetically Engineered Foods Could Alleviate Nutritional Deficiencies
There are over two billion people around the world that don't get the recommended levels of minerals and vitamins in ...
OCT 24, 2020
Genetics & Genomics
Cord Blood Samples Reveal More About the Genetics of Autism
OCT 24, 2020
Cord Blood Samples Reveal More About the Genetics of Autism
The activity of genes in our genome is controlled by many factors, one of which are chemical tags or structural changes ...
OCT 25, 2020
Genetics & Genomics
A Purr-fect Domestic Cat Genome
OCT 25, 2020
A Purr-fect Domestic Cat Genome
There are thought to be more than 94 million cats in the US alone. Researchers have now improved the reference genome se ...
Loading Comments...