In the study, published online in the journal Aging Cell, the researchers identified a protein interaction that controls the silencing of Oct4, a key transcription factor that is critical to ensuring that embryonic stem cells remain pluripotent. The protein, WRNp, is the product of a gene associated with Werner syndrome, an autosomal recessive disorder hallmarked by premature aging. The gene expression in Werner syndrome closely resembles that of normal aging, and as a result, Werner syndrome is an accepted model of aging.
They first found that WRNp accumulates at the Oct4 promoter in differentiating stem cells. They then found that WRNp interacts with another protein called Dnmt3b to control DNA methylation at the Oct4 promoter, according to researchers led by René Daniel, M.D., Ph.D., associate professor of Medicine.
Previously, Dnmt3b was identified to be a key player in the DNA methylation of the Oct4 promoter. DNA methylation of the Oct4 promoter inactivates the Oct4 gene. The inactivation, or silencing, of this gene is necessary for stem cell differentiation.
"We showed that the depletion of WRNp blocked the recruitment of Dnmt3b to the Oct4 promoter, and resulted in reduced methylation," Dr. Daniel said. "The reduced DNA methylation was associated with continued Oct4 expression, which resulted in attenuated differentiation."
Until now, the focus of studies on the role of WRNp in aging has been on telomeres. These studies have shown that telomeres undergo accelerated shortening and loss in Werner syndrome cells. But it remains to be shown if this is the major role that WRNp plays in the aging process.
"These results reveal a novel function of WRNp, and demonstrate that WRNp controls a key step in pluripotent stem cell differentiation," Dr. Daniel said. "Our data support the emerging hypothesis that attenuated stem cell differentiation is involved in aging. This lack of differentiated cells may contribute to failure to maintain organ or tissue function in the later stages of life."
Emily Shafer | EurekAlert!
Closing in on advanced prostate cancer
13.12.2017 | Institute for Research in Biomedicine (IRB Barcelona)
Visualizing single molecules in whole cells with a new spin
13.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong
Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
13.12.2017 | Health and Medicine
13.12.2017 | Physics and Astronomy
13.12.2017 | Life Sciences