The selection arena in early human embryos resolves the pluripotent inner cell mass

The selection arena in early human blastocysts resolves the pluripotent inner cell mass. We do not understand much about the earliest stages of human development. On a gross level, there is evidence for apoptosis, but the nature of the affected cell types is unknown. Perhaps most importantly, the inner cell mass (ICM), from which the foetus is derived and hence of interest in reproductive health and regenerative medicine, has proven hard to define. Here we provide a multi-method analysis of the early human embryo to resolve these issues. Single-cell analysis (on multiple independent data sets), supported by embryo visualization, uncovers a typical previously uncharacterised class of cells lacking commitment markers that segregate after embryonic gene activation and shortly after undergo apoptosis. The discovery of this cell type allows us to clearly define their viable ontogenetic sisters, these being the cells of the inner cell mass (ICM). While ICM is characterized by the activity of an Old non-transposing endogenous retrovirus (HERVH) that acts to suppress Young transposable elements, the new cell type, by contrast, expresses transpositionally-competent Young elements and DNA-damage response genes. As the Young elements are RetroElements and the cells are excluded from the developmental process, we dub these REject cells. With these and ICM characterised by differential mobile element activities, the human embryo may be a "selection arena" in which one group of cells selectively die while other less damaged cells persist.