Regulation of Embryonic Stem Cell Self Renewal by the Zscan4 Family of Zinc Finger Proteins

Stem cells are present within our bodies throughout our lives and are very important because they make sure that as damaged and worn out cells die, there is a supply of new cells to replace them. Some organs and tissues have a tremendous capacity to replace cells, e.g. the blood, the liver and the gut. However, organs such as the brain and heart have very limited capacity for repair and regeneration. Stem cells have been isolated from a variety of adult sources including bone marrow, gut and muscle and also from early stage embryos. Research has shown that these stem cells have two remarkable properties. They can divide to form two identical stem cells (self-renew themselves) or they can form many other types of cells (differentiate). There is currently great interest in harnessing these unique properties because by using stem cells it may be possible to generate cells in the laboratory, that can be used to either replace damaged tissues inside the body or to identify safer and more effective medicines. Many chronic diseases cannot currently be effectively treated because loss of cells is the underlying cause, e.g. type 1 diabetes. Parkinson?s disease and stem cell-based therapies offer exciting alternative treatments for disease sufferers. However, much more research needs to be carried out to understand stem cell behaviour before such advances will be brought into modern day medical practice. The overall objective of this research proposal is to understand in greater detail the processes that control the ability of stem cells to renew themselves. Several signals within stem cells are known to be important in controlling self-renewal and our recent studies have identified a new regulator of this process. We identified this new regulator by analysing genes whose expression changes at early times after embryonic stem cells start to differentiate. This gene is predicted to control the regulation of other genes and we wish to now investigate this in more detail. Using cellular, genetic and biochemical experiments we will determine how this gene works in embryonic stem cells. By understanding the processes that control self-renewal of stem cells in more detail we should be able to apply this knowledge to the exploitation of stem cells in regenerative medicine and drug discovery. Stem cell-based strategies offer real hope for the sufferers of many chronic diseases and the research proposed here could be of real benefit in the medium to longer-term.