Because human embryos cannot legally be cultured longer than 14 days in the UK (see BioNews 1083 and 1086), if scientists wish to study them the embryos must be conceived naturally and donated following a termination. As most potential donors do not know they are pregnant at this stage and so would not be seeking termination, studies on human embryos at and shortly beyond a phase known as gastrulation, which occurs around two weeks after fertilisation, are extremely rare.
Professor Shankar Srinivas of the University of Oxford and corresponding author of the study said: 'Our body is made up of hundreds of types of cells. It is at this stage that the foundation is laid for generating the huge variety of cells in our body – it's like an explosion of diversity of cell types.'
The study, published in Nature and performed by researchers at the University of Oxford and the Helmholtz Zentrum München, Germany, focused on a single donated embryo staged at 16–19 days post-fertilisation. Researchers separated the embryo into its constituent cells, sequencing the messenger RNA of a total of 1195 individual cells to create a highly detailed map of gene expression across cell types.
Generation of high-resolution data of the molecular mechanisms governing this step of development is especially crucial. This is the point at which a cluster of relatively indeterminate cells begins to differentiate into different parts of the body.
Sarah Norcross, director of the Progress Educational Trust, said: 'It is extremely rare for specimens of human embryos at this 16–19 day stage to become available to researchers. The fact that this is unlikely to happen again in the foreseeable future makes this study all the more precious, and adds to the case for extending the 14-day rule, so that early human development can be better understood through the study of embryos that have been cultured in the laboratory beyond 14 days.'
The work has provided a fuller picture of the path from stem cell to tissue type specification in humans. This enhanced understanding could inform treatment and diagnosis of developmental diseases and efforts to grow human tissues and organs outside the body.
The results have also revealed similarities between humans and model research organisms at this stage of embryogenesis. Dr Richard Tyser of the University of Oxford and first author of the paper said: 'Reassuringly, we have now been able to show that the mouse does model how a human develops at the molecular level. Such models were already providing valuable insights, but now this research can be further enriched by the fact we're able to cast light into that black box and more closely see how it works in humans.'
However, many differences remain between the mechanisms revealed by this work and those which take place in other animals. The findings highlight the importance of studying this step of embryogenesis in humans and the effect barriers to this may have on scientific progress.
Norcross concluded: 'If and when the 14-day rule is extended, this study will provide an invaluable reference point, so that similarities and differences between embryos cultured in vitro and in vivo can be better understood and taken into account. We have an opportunity here to open the "black box" of human development, study gastrulation and related processes, improve our understanding and treatment of disease, and perhaps improve our understanding of miscarriage and infertility as well. We should seize this opportunity.'
Others were keen to emphasise the importance and significance of the study too. 'The new study provides a Rosetta Stone for developmental biologists,' Dr Peter Rugg-Gunn, of the Babraham Institute, in Cambridge said who was not involved in the study. 'The new study is already yielding important new insights into how the early cell lineages are formed and positioned in the developing embryo... This information provides new leads to understand why these processes sometimes go wrong during pregnancy, which can result in developmental defects in some babies.'