We measured total transcription in the inner cell mass (ICM) and the trophectoderm (TE) of the human embryo to understand the mechanisms underlying TE commitment. We describe here discovery of a function for class I HLA-E and HLA-G receptors in lineage commitment. The data - conserved expression between hES cells and the in vitro differentiated TE - suggested HLA-L marked primitive tissues. We recently demonstrated evidence supporting a developmental function for MHC receptors MICA and MICB.