By switching on specific genes governing the timings of cell-type specification during embryo development in mice, scientists at the University of Bonn, Germany, have been able to recreate primary stem-cell types found in early embryos. When cultured together, the cells organise themselves into a developing complex resembling early embryogenesis.
'Embryo development is largely based on self-organisation,' explained Professor Hubert Schorle of the Department of Developmental Pathology at the University of Bonn and corresponding author of the paper published in Nature Communications. 'Each cell releases messenger substances into its environment and thereby helps determine the fate of its neighbours.'
When a fertilised egg begins to divide, it goes on to produce three primary types of stem cells which differentiate to form layers of the early embryo. Scientists have previously used these separate cell types to form a group of cells that can spontaneously organise itself. However, this previous work involved a delicate balance of culturing the different cell types in compatible growth conditions and did not always yield reliable results.
By starting with only one type of stem cell, embryonic stem cells, Professor Schorle's team activated certain genes inducing them to take on the identities of other stem cells found in early embryos. These new cell types can then be mixed to form what the researchers name an 'embryoid'.
'This resembled a five-day-old mouse embryo,' said Arik Horne from the German Centre for Neurodegenerative Diseases and the LIMES Institute at the University of Bonn, and co-first author of the paper. 'The disordered mixture of the three cell types had therefore evolved into a strictly ordered structure, much like the one that normally emerges from a fertilised egg.'
Using fluorescent proteins to mark each stem cell type, the researchers were able to track how these cells integrated and gave rise to different regions of the developing embryo. They also used sequencing technology to analyse the gene expression patterns across the 'embryoids', revealing the cells' developmental paths.
The team hope that their findings will provide an effective platform for studying various aspects of embryo development – they plan to extend the method to primate embryos. Looking to the medium term, they propose that 'embryoids' will provide an alternative to the use of animals in testing compounds harmful to fetal development.