Facilitating reprogramming by defined factors of nullipotent cells
Final Report Abstract
During the development of a complex organism, its cells will become increasingly and irreversibly more specialised. However, it has been discovered in recent years that the restrictions on the potential of specialised cells to develop into different kinds of cells can be lifted by artificially forcing the expression of four proteins. These proteins, Sox2, Oct3/4, Klf4 and c-Myc, are characteristically found in non-specialised stem cells and appear to be sufficient to initiate the de-specialisation of many kinds of cells of mice and men. The resulting cells have similar properties as stem cells and are thought to be a very promising source for medical research and application in personalised medicine. As yet, many questions remain open about the nature of the ‘reprogramming’ process and how to further improve it. It is also still unknown if the resulting cells have all the properties of stem cells and if their medical application is safe. Only a minority of cells that express the reprogramming factors become fully stem cell-like. In this project factors were identified that may improve the reprogramming efficiency. These factors included genes which control the long-term modification of gene expression and regulators of gene expression that appear at a late stage of the reprogramming process. In addition, a network of protein interactions was identified that could assist in understanding the differences between incomplete and fully reprogrammed cells. Lastly, a new protocol for the application of chemical compounds appeared to advance reprogramming.
