Ancient Viral DNA Necessary For Pluripotency in Embryonic Stem Cells
In an intriguing study published recently in the journal Nature, scientists discovered that ancient pieces of viral DNA present in our human genome were responsible for pluripotency in embryonic stem cells.
Embryonic stem cells are derived from very early developing embryos. They have the ability to specialize into types of cell that will eventually make up certain parts of the body such as bone, nervous system cells or organs such as the lungs. This capability is called pluripotency. Intriguingly, scientists discovered that ancient pieces of viral DNA that are present in our genome are required for pluripotency. These sequences of DNA are called human endogenous retroviruses (HERVs). HERVs were discovered around the 1960s, and since then it has been discovered that sequences such as these make up around 8% of our total human genome. HERVs are the result of infection that occurred long ago in our ancestors by a family of viruses called retroviruses. There are many types of retrovirus, but HIV is probably the most well known. In order for these viruses to successfully become a heritable part of our genome they had to infect germ cells; these are cells that will become gametes (sperm or egg cells). If they only infected non-germ cells (called somatic cells) then they wouldn’t have been passed on. Since their introduction into our genome, they accumulated mutations which meant that they could no longer form infectious viral particles. They have, however, frequently been accused of an involvement in certain chronic diseases such as cancer and autoimmunity.
In order to investigate the role of a particular type of HERV, called HERVH, the scientists designed small pieces of RNA that could silence, or suppress, the expression from these sequences in human embryonic stem cells (hESCs). They found that this dramatically altered the shape of the cells and that they could only differentiate into one particular type of cell. This type of cell resembled fibroblast cells which are found in connective tissue. They also found that markers for pluripotency were suppressed in these cells. Furthermore, they also found that suppression of HERVH also affected induced pluripotent stem cells, which suggested not only that HERVH was necessary for pluripotency in hESCs, but it was also needed for the acquisition of pluripotency in somatic (non germ) cells, which is really interesting and unexpected.
It seems that there is a growing body of evidence suggesting these pieces of viral DNA that were once thought of as “junk” DNA can play surprising and diverse roles in humans. Although we can’t extrapolate this data to make inferences for the roles that HERVs may play in other animals, it seems that they certainly play a part in human development, which is very exciting news. Hopefully this will spark more research into this interesting area of science.