Genetic 'signatures' of early-stage embryos confirm that our development begins to take shape as early as the second day after conception, when we are a mere four cells in size, according to new research published in the journal Cell. Although they seem to be identical, the cells of the two day-old embryo are already beginning to display subtle differences.

Once an egg has been fertilized 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.

New research 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.

Live-cell tracking demonstrates that cells with decreased Sox21 yield more extra-embryonic than pluripotent progeny. Consistently, decreasing Sox21 results in premature upregulation of the differentiation regulator Cdx2, suggesting that Sox21 helps safeguard pluripotency.

Furthermore, Sox21 is elevated following increased expression of the histone H3R26-methylase CARM1 and is lowered following CARM1 inhibition, indicating the importance of epigenetic regulation.

Therefore, these results indicate that heterogeneous gene expression, as early as the 4-cell stage, initiates cell-fate decisions by modulating the balance of pluripotency and differentiation.

http://www.cell.com/cell/fulltext/S0092-8674(16)30061-7