Discovery reveals more about stem cells' immortality 24 August 2009 Scientists part-funded by the Wellcome Trust have discovered a key link in the chain of events that allows embryonic stem cells to transform into different types of cells in the body. A protein called Nanog has, in recent years, emerged as a key player in the system that keeps stem cells in a constant, undifferentiated 'pluripotent' form. Now, researchers from the Wellcome Trust Centre for Stem Cell Research at the University of Cambridge and colleagues have determined that its role is as a final controller in the process. The findings help us understand more about how stem cells work, which will aid scientists' efforts to harness the cells for medical applications. Nanog was first isolated in 2003 and identified as playing an important part in stem cell pluripotency. But scientists didn't know its exact role in the process. In the new study, the researchers showed that Nanog acts like a conductor in charge of an orchestra of genes and proteins during the final performance. All must play at the right time in perfect harmony for the cell to 'refresh' into a pluripotent state. Without Nanog, a stem cell cannot maintain an immortal pluripotent state. Similarly, without it, attempts to reprogram adult cells to become pluripotent fail. The protein must be present specifically during the final reprogramming phase when other key factors are already present, otherwise the cell becomes 'stuck' in a halfway state of development. "Our research shows that this unique protein flips the last switch in a multi-step process that gives cells the very powerful property of pluripotency," said Dr Jose Silva from the Wellcome Trust Centre, who led the research. "The next challenge is to find out exactly how Nanog influences all these other molecules." "If we want to create efficient, safe and reliable ways of generating these cells for medical applications, we need to understand the process. Our research provides additional clues as to how it occurs." Scientists hope that stem cell research will one day enable us to transform adult cells into pluripotent stem cells in the body. These could then be turned into any other type of body cell, from liver cells to nerve cells. This could form treatments for diseases such as diabetes, Parkinson's disease or Alzheimer's disease. Image: Scanning electron micrograph of a human embryo exposing the embryonic cells. Credit: Yorgos Nikas, Wellcome Images Reference Silva J et al. Nanog is the gateway to the pluripotent ground state. Cell 2009; 138(4):722-37