How do the precursors of sperm and eggs form during human development? It’s a question that has puzzled scientists for over two centuries. Now researchers at the University of Nottingham and the Gurdon Institute, University of Cambridge have uncovered the origins of these elusive cells.
Their research - ‘Principles of early human development and germ cell program from conserved model systems’ – published in Nature on Wednesday 7 June 2017, could lead to a paradigm shift in our understanding of how early development occurs in mammals.
They have shown, for the first time, that the interplay between two key genes is critical for the formation of the germline precursors – the cells that are key to the preservation of a species - and this ‘genetic cocktail’ changes in different species. As a result, scientists have discovered clear differences between the early development of humans and mice and a much closer relationship between humans and pigs. These findings could change the way we study early human development and improve our understanding of genetic diseases.
The study shows that this mechanism is conserved in humans, monkeys and pigs.
The combination of human-pig models for early development and cell fate decisions likely reflect critical events in early human embryos in the womb. Altogether, knowledge gained from this approach can be applied to regenerative medicine for the derivation of relevant human cell types that might be used to help understand and treat human diseases, and to understand how mutations that disrupt early development can result in human diseases.
Dr Ramiro Alberio, from the School of Biosciences at the University of Nottingham, said: “We’ve shown how precursors to egg and sperm germ cell arise in species with similar embryo development. This suggests that the pig can be an excellent model system for the study of early human development as well as improving our understanding of the origins of genetic disease.”
Professor Azim Surani, in the Gurdon Institute at the University of Cambridge, said: “Animals with conserved embryology can inform on the genes involved in human embryo development and these mechanisms can be recapitulated in the laboratory using embryonic stem cells. Using this system, we were able to uncover the fundamental principles of how specific genes can influence cellular identity.”
Culmination of 10 year’s work
For Dr Alberio this is the culmination of 10 years of work on embryo development. When he started these studies very little was known about the molecular aspects of pig embryogenesis. Since then his research group has developed tools and novel understanding of how early embryos form. His research focusses on the very early decisions made by the cells in the embryo — the very early switch of an embryonic cell towards differentiation, and on how similar these processes are in different mammals.
Dr Alberio said: “We show how studying the pig embryo can help us design new methods for the differentiation of human sperm and eggs in a dish. The findings of our research will help scientists improve our understanding of the origins of genetic diseases such as germ cell tumours, fetal abnormalities and certain types of infertility.”
The research was supported by Wellcome and the Biotechnology and Biological Sciences Research Council.
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Notes to editors: The University of Nottingham has 43,000 students and is ‘the nearest Britain has to a truly global university, with a “distinct” approach to internationalisation, which rests on those full-scale campuses in China and Malaysia, as well as a large presence in its home city.’ (Times Good University Guide 2016). It is also one of the most popular universities in the UK among graduate employers and was named University of the Year for Graduate Employment in the 2017 The Times and The Sunday Times Good University Guide. It is ranked in the world’s top 75 by the QS World University Rankings 2015/16, and 8th in the UK for research power according to the Research Excellence Framework 2014. It has been voted the world’s greenest campus for four years running, according to Greenmetrics Ranking of World Universities.
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