Researchers find 'missing link' stem cells
Wednesday 27 June
Scientists are one step closer to understanding how stem cells work. Two independent teams of researchers based at Cambridge University and Oxford University have discovered a new type of embryonic stem cell in mice and rats which is very similar to human embryonic stem cells. Both papers are published online this week in Nature.
The discovery, and its virtually simultaneous verification, will change the way we think about human embryonic stem cells: it’s likely to accelerate understanding of stem cell development and help the derivation of stem cells in other species - including livestock and disease-prone mice used in research - thereby providing better models for researchers involved in stem cell research.
Up until now, embryonic stem cells derived in humans and mice had looked different and not behaved in the same way. The main thing they had in common was their pluripotency, that is to say their ability to turn into any type of cells: nerve cells, blood cells, among others. But researchers had found that mouse and human stem cells maintained this state in quite different ways, which required distinct techniques for their growth in culture.
The two teams found that when mouse stem cells are derived from the innermost cell layer (epiblast) of the one week old rodent embryo, rather than from the more usual early blastocyst stage (3-4 days after conception), they actually resembled human embryonic stem cells and had many of the same properties. The new mouse stem cells taken from this later stage of development could be maintained using the same growth factors as those used in the culture of human embryonic stem cells. The two British teams were able to produce stable cell lines which were used to work out how the novel cells remain pluripotent or begin to specialise during early development. Finally, these new stem cells also looked very similar to human embryonic stem cells under the microscope.
Rat epiblast stem cell colony (I. Gabrielle M. Brons)
Further verification studies were then undertaken with researchers at UCL (University College London) and the US National Institutes of Health to analyse the molecular characteristics of the newly-derived stem cells. Their evidence further confirmed the similarity of the novel mouse stem cells to human embryonic stem cells.
The ‘epiblast stem cells’, as they have been named, constitute the “missing link between mouse and human embryonic stem cells” according to Professor Roger Pedersen whose Medical Research Council funded laboratory led the Cambridge team. “On a molecular level, epiblast stem cells are more similar to human embryonic stem cells than to mouse embryonic stem cells. The differences between mouse and human embryonic stem cells that we had attributed to species differences may actually come down to the developmental stages from which the cells emerge,” added Professor Pedersen.
These two studies provide scientists with a better insight into pluripotency and specialisation - the path a stem cell follows to become a mature blood cell or bone cell. The discovery of epiblast stem cells will also offer new methods for building on that understanding. Because epiblast stem cells are so similar to human embryonic stem cells they will provide better models for human ES cells and will help move stem cell research toward potential therapies.
Sir Richard Gardner, who led the Oxford team added, “These findings suggest that human embryonic stem cells originate at a later stage of development than previously thought. Having both studies reach the same conclusions at the same time allows other researchers to use this new information immediately in their research. The fact that both studies made this discovery almost simultaneously is a clear sign of the momentum picking up in stem cell research. We are reaching a critical mass of understanding about these cells which should enable us to make the most of them in coming years.”
In addition to revealing a novel type of pluripotent stem cell, the current study by the Cambridge team is the first report of derivation of pluripotent stem cells from rat embryos. So far embryonic stem cells had mainly been derived from mice and from primates, with limited success in other species. There is now hope that epiblast stem cells could be derived from other species, including livestock, and from genetic strains like diabetes-prone mice, also studied by the Cambridge team, which had so far not yielded pluripotent stem cells by other methods.
“Our hope is that pinpointing the developmental stage when human embryonic stem cells originate will help scientists who are using stem cells to develop cures for injuries and disease,” said Professor Pedersen.
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Notes to editors:
1. Publication details
Derivation of Pluripotent Epiblast Stem Cells from Mammalian Embryos. Nature. Received 15 January; accepted 24 May 2007. Published online 27 June 2007.
I. Gabrielle M. Brons, Lucy E. Smithers, MatthewW. B. Trotter, Peter Rugg-Gunn, Bowen Sun, Susana M. Chuva de Sousa Lopes, Sarah K. Howlett, Amanda Clarkson, Lars Ahrlund-Richter, Roger A. Pedersen & Ludovic Vallier
New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature. Received 30 April; accepted 31 May 2007. Published online 27 June 2007.
Paul J. Tesar, Josh G. Chenoweth, Frances A. Brook, Timothy J. Davies, Edward P. Evans, David L. Mack, Richard L. Gardner & Ronald D. G. McKay
2. Further collaborations
The Cambridge and Oxford groups collaborated with other stem cell researchers who carried out further molecular analyses to characterise epiblast stem cells and compare them with mouse and human embryonic stem cells. The Cambridge group collaborated with researchers at University College London, and the Oxford group collaborated with researchers at the National Institutes of Health in the USA.
3. Funding
- The principal funder of the University of Cambridge project was the Medical Research Council in partnership with the Juvenile Diabetes Research Foundation; additional funding was provided by the US National Institutes of Health;
- The University College London contributions were funded by a Functional Genomics grant from the Wellcome Trust.
- The University of Oxford project was funded by the Wellcome Trust and the Royal Society.
- The US contributions were funded by the National Institutes of Health.
4. The Cambridge Stem Cell Initiative, Cambridge University
For further information, visit www.stemcells.cam.ac.uk
Ref: MRC/25/07
