Scientists have uncovered a vital link in the chain of events that gives stem cells their remarkable properties.
Researchers from the Wellcome Trust Centre for Stem Cell Research at the University of Cambridge have pinpointed the final step in a complex process that gives embryonic stem cells their unique ability to develop into any of the different types of cells in the body (from liver cells to skin cells). Their findings, published today in the journal Cell, have important implications for efforts to harness the power of stem cells for medical applications.
In the last few years, huge strides have been made in stem cell research. Scientists are now able to transform adult skin or brain cells into embryonic-like stem cells in the laboratory. Just like natural embryonic stem cells, these reprogrammed cells can make all the body's cell types. This extraordinary ability is known as pluripotency - 'having several potential outcomes'. It is the basis for the hope that stem cells will one day help fight illnesses like diabetes, Parkinson's or Alzheimer's disease.
Despite such exciting developments, scientists still have only a very basic understanding of how cells become pluripotent. Dr Jose Silva, who led the Cambridge research with his colleague Dr Jennifer Nichols, says: "Exactly how pluripotency comes about is a mystery. 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. "
The researchers, funded by public and charitable sources, studied how the rather poetically named protein Nanog helps give cells pluripotency. Nanog takes its name from the celtic phrase 'Tir Nan Og', or 'land of the ever young'. It was identified as a key player in pluripotency in 2003, but until now its exact biological role remained unclear.
Dr Silva says: "It was clear that Nanog was important, but we wanted to know how it works. 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."
Without Nanog, cells remain in a sort of half-way house. As a result, the embryo can't develop and attempts to reprogramme adult cells fail.
But Nanog does not work alone. It appears to be the conductor in charge of an orchestra of genes and proteins that must all play at the right time and in perfect harmony to create pluripotency. Dr Silva added: "The next challenge is to find out exactly how Nanog influences all these other molecules."
This research was supported by the Wellcome Trust, the Biotechnology and Biological Sciences Research Council, and the EC Framework 7 project EuroSyStem.
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Notes for Editors:
1) The paper, 'Nanog is the Gateway to the Pluripotent Ground State', will be published in the 21 August edition of Cell by Jose Silva, Jennifer Nichols et al. Image available upon request.
2) Nanog was isolated in 2003 by two research groups. For more information, see the following publications:
Chambers et al, Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells, Cell (2003), doi:10.1016/S0092-8674(03)00392-1
Mastsui et al, The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells, Cell (2003), doi:10.1016/S0092-8674(03)00393-33)
3) This research was supported by the Wellcome Trust, the Biotechnology and Biological Sciences Research Council, and the EC Framework 7 project EuroSyStem. Austin Smith, one of the key contributing researchers, is a Medical Research Council Professor.
4) The Wellcome Trust Centre for Stem Cell Research is based at the University of Cambridge and exists to provide outstanding scientists with the opportunity to undertake ground-breaking research into the fundamental biological properties and the biomedical potential of stem cells. With core support from the Wellcome Trust and the Medical Research Council, the Centre is an exceptional environment for fundamental stem cell research. www.cscr.cam.ac.uk
5) The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending around £600 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. http://www.
6) The Medical Research Council supports the best scientific research to improve human health. Its work ranges from molecular level science to public health medicine and has led to pioneering discoveries in our understanding of the human body and the diseases which affect us all. www.mrc.ac.uk
7) The Biotechnology and Biological Sciences Research Council (BBSRC) is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £450 million in a wide range of research that makes a significant contribution to the quality of life for UK citizens and supports a number of important industrial stakeholders including the agriculture, food, chemical, healthcare and pharmaceutical sectors. BBSRC carries out its mission by funding internationally competitive research, providing training in the biosciences, fostering opportunities for knowledge transfer and innovation and promoting interaction with the public and other stakeholders on issues of scientific interest in universities, centres and institutes.
The Babraham Institute, Institute for Animal Health, Institute of Food Research, John Innes Centre and Rothamsted Research are Institutes of BBSRC. The Institutes conduct long-term, mission-oriented research using specialist facilities. They have strong interactions with industry, Government departments and other end-users of their research. For more information see: http://www.
8) EuroSyStem is an EC funded partnership of 25 research groups in eight countries. Its focus is on answering questions in fundamental stem cell biology. Its partners combine computational and biological expertise to drive the generation of new knowledge on the characteristics of normal and abnormal stem cells. www.eurosystemproject.eu