In accordance with the researchers from the Regenerative Medicine and the Department of Medicine, Thomas Jefferson University and the Centre for Stem Cell Biology, a gene which was shown to play a part in the process of aging seems to play an important role in regulating the differentiation of embryonic stem cells.
In the research that was published in the online journal Aging Cell, the researchers identified a protein interaction that regulates the silencing of Oct4. The Oct4 is an important transcription factor that is vital in order to make sure that the embryonic stem stays pluripotent. The protein WRNp is the result of a gene that is associated with the Werner syndrome. The Werner syndrome is an autosomal recessive disorder that is hallmarked by a premature aging. The gene expression in the Werner syndrome strongly looks like that of normal aging, and as a consequence, the Werner syndrome is an established model of aging.
They initially discovered that WRNp gathers at the Oct4 promoter in distinguishing stem cells. Afterwards they found out that WRNp collaborates with another protein known as Dnmt3b to regulate DNA methylation at the Oct4 promoter, based on what researchers that has been led by René Daniel, PhD who is also an associate professor of Medicine.
In the past, Dnmt3b was recognised as having a key role in the DNA methylation of the Oct4 promoter. The DNA methylation of the Oct4 promoter stops the triggering of the Oct4 gene. This inactivation also known as silencing of this gene is crucial for the differentiation of stem cells.
Doctor Daniel stated that they have shown that the depletion of WRNp stopped the recruitment of Dnmt3b to the Oct4 promoter and as result there is a reduction in methylation. It is the reduced DNA methylation that was related with continued Oct4 expression, whose result was attenuated differentiation.
Till now, the studies regarding the role of WRNp in the aging process have focused on telomeres. These studies have illustrated that telomeres go through an increased shortening and also experience a loss in Werner syndrome cells. However, it remains to be proven if this is in fact the key role that WRNp has to play in the aging process.
Doctor Daniel further explains that these results unveil a new function of WRNp, and show that WRNp has an influence on a crucial step in pluripotent stem cell differentiation. Their data supports the rising hypothesis that attenuated stem cell differentiation is in fact involved in aging. This short of differentiated cells may add to the failure in maintaining tissue or organ function in life later on.
Source: Jefferson Hospital and Escience News
Thu, Jul 1, 2010
Anti Aging, Nanotechnology, Stem cells