Embryo development: Some cells are more equal than others even at four-cell stage

Once an egg has been fertilised by a sperm, it divides several times, becoming a large free-floating ball of stem cells. At first, these stem cells are 'totipotent', the state at which a stem cell can divide and grow and produce everything--every single cell of the whole body and the placenta, to attach the embryo to the mother's womb. The stem cells then change to a 'pluripotent' state, in which their development is restricted to generating the cells of the whole body, but not the placenta. However, the point during development at which cells begin to show a preference for becoming a specific cell type is unclear.

Now, in a study published in the journal Cell, scientists at the University of Cambridge and the European Bioinformatics Institute (EMBL-EBI) suggests that as early as the four-cell embryo stage, the cells are indeed different.

The researchers used the latest sequencing technologies to model embryo development in mice, looking at the activity of individual genes at a single cell level. They showed that some genes in each of the four cells behaved differently. The activity of one gene in particular, Sox21, differed the most between cells; this gene forms part of the 'pluripotency network'. The team found when this gene's activity was reduced, the activity of a master regulator that directs cells to develop into the placenta increased.

"We know that life starts when a sperm fertilises an egg, but we're interested in when the important decisions that determine our future development occur," says Professor Magdalena Zernicka-Goetz from the Department of Physiology, Development and Neuroscience at the University of Cambridge. "We now know that even as early as the four-stage embryo - just two days after fertilisation - the embryo is being guided in a particular direction and its cells are no longer identical."

Dr John Marioni of EMBL-EBI, the Wellcome Trust Sanger Institute and the Cancer Research UK Cambridge Institute, adds: "We can make use of powerful sequencing tools to deepen our understanding of the molecular mechanisms that drive development in individual cells. Because of these high-resolution techniques, we are now able to see the genetic and epigenetic signatures that indicate the direction in which early embryonic cells will tend to travel."