The scientists of the Genome Institute of Singapore (GIS), a biomedical research institute of the Agency for Science, Technology and Research (A*STAR), along with their colleagues of the Nanyang Technological University, National University of Singapore, Princeton University and Duke-NUS Graduate Medical School have newly found out that the viruses that “invaded” the human genome millions of years before have altered the way genes activated and deactivated within human embryonic stem (ES) cells. This study offers ultimate evidence of a theory that was initially proposed in the ‘50s by Barbara McClintock, the Nobel Laureate in physiology and medicine. She hypothesized that mobile pieces, transposable elements of the genetic material (DNA) like viral sequences, could be “control elements” that impact the regulation of gene once it was inserted in the genome.
This discovery is a vital contribution to the progress in stem cell research and to its prospective regenerative medicine. The study was led by Dr Guillaume Bourque, GIS Senior Group Leader and has been published in the June 2010 issue of Nature Genetics.
By making use of novel sequencing technologies, the scientists examined the genomic locations of OCT4, NANOG and CTCF, three regulatory proteins that are found in the human as well as mouse embryonic stem (ES) cells. Fascinatingly, whilst the scientists discovered a great deal of similarities, they also found several differences in the ways and the kinds of genes that are being controlled in human beings. Especially, it was found out that particular kinds of viruses that inserted themselves within the human genomes millions of years before have radically altered the gene regulatory network in human stem cells.
Doctor Cedric Feschotte, an associate Professor at the University of Texas Arlington, said that this study is an experimental and computational tour de force. It offers irrefutable proof that a number of transposable elements that are too frequently dismissed as simply junk DNA are significant components of a regulatory code that underlies human development.
The comparisons that have been made between the mouse and human model system during the study of gene regulatory networks lend a helping hand in advancing the comprehension of the way stem cells differentiate into a variety of cell types of the body. According to Doctor Bourque, this comprehension is vital in the enhanced development of regenerative medicine for illnesses like leukaemia and Parkinson’s disease. He further advances that in spite of the benefits of making use of mouse ES cells during the study of gene regulatory networks; there is a need for more in-depth research that concentrate more directly on human stem cells. This is due to the innate challenges of adapting the results of the studies done from one species to that of the next. There is a need for more research to be done in both non-human and human primate stem cells for discoveries on stem cells to be utilized in clinical application.
In accordance to Professor Raymond L. White, Rudi Schmid Distinguished Professor of Neurology at the University of California, the paper recount very thrilling new findings that set up a novel and basically distinct mechanisms for regulating gene expression. By making a comparison between the genomes of mouse with that of human beings, the scientists were able to demonstrate that the binding sites for gene regulatory factors are very frequently not in the exact place between the two species. This in itself would be indeed much unexpected; however, the investigators go a step further and show that several of the sites are embedded in a class of DNA sequences that are known as “transposable” elements due to their ability to go to novel places in the genome. There are many such elements that are believed to be the evolutionary remaining of viral genomes; nevertheless, it was very amazing to learn that they were actually carrying binding sites for regulatory elements to novel locations. These alterations in regulation would be anticipated to create key changes in the organisms which carry them. In fact, many are of view that regulatory alterations are at the centre of speciation and may have played a great role in the evolution of humans from their ancestors. This is probably going to be a landmark paper in the field.
The Director of the Unites States Department of Energy Joint Genome Institute as well as the Director of the Genomics Division at Lawrence Berkeley National Laboratory at Berkeley, Doctor Eddy Rubin added that this study making use of a genomics strategy, that is comparative in nature, found out significant human particular properties of the regulatory network in human ES cells. This piece of information is considerable and should contribute to assist in moving the regenerative medicine field forward.
Source: Escience News and A Star
Fri, Jul 2, 2010
Immortality, Nanotechnology, Stem cells