Scientists at the University of Edinburgh’s MRC Centre for Regenerative Medicine (CRM) have made a fundamental discovery about how the properties of embryonic stem cells are controlled. The study, which focuses on the process by which these cells renew and increase in number, could help research to find new treatments.
Researchers found that a protein, which switches on genes to allow embryonic stem cells to self-renew, works better when the natural occurring level of the protein is reduced. It was previously thought that once levels of this protein – called Oct4 – were reduced the numbers of new stem cells being produced would also fall.
Image shows a colony of embryonic stem cells with the protein Oct4 shown in red and Nanog, a protein that determines stem cell renewal efficiency, in green.
During embryonic development, cells that have the capacity to become any cell type in the body – called pluripotent stem cells – can either renew themselves by multiplying in number or differentiate to become cells found in different parts of the body, for instance skin or liver.
This need for pluripotent cells to increase in number is important so that there is a sufficient supply of them to be differentiated into other cell types. Scientists found that when there were lower levels of Oct4, the protein bound much more tightly to key parts of DNA in cells. The strong attraction of Oct4 to these sections of DNA enabled the efficient switching on of key genes that caused pluripotent stem cells to renew.
The findings will inform stem cell research and give scientists greater control over stem cell behaviour, an essential step when looking to find treatments for conditions like motor neurone disease, multiple sclerosis and heart disease.
CRM Professor Ian Chambers, who led the study, said: “What we found was a complete surprise, as we thought that when levels of this key protein were reduced the numbers of pluripotent stem cells being generated would also fall. Instead, it appears that when the levels of Oct4 are lower, the balance is tipped in favour of self-renewal over stem cell differentiation.”
Post-Doc Dr Violetta Karwacki-Neisius, first author on the paper, continued: “When I first made the discovery I was very excited but also needed to convince myself that what I saw was real. Everybody thought that small variations in Oct4 didn’t matter, but our study clearly shows that even the smallest variations have an effect on the number of pluripotent stem cells that are made.”
“Together with my CRM colleagues and other collaborators in Edinburgh and Singapore I worked hard to make sure we understood the underlying mechanisms better. I hope our efforts will contribute towards a deeper understanding of how stem cells can be cultured in the laboratory.”
The study, published on 2 May 2013 in the journal Cell Stem Cell, was funded by the Medical Research Council, the Wellcome Trust, the Biotechnology and Biological Sciences Research Council and the Human Frontier Science Programme.