Lineage segregation in human pre-implantation embryos is specified by YAP1 and TEAD1

We know that polarity and YAP1 play a key role in trophectoderm initiation in compacted human embryos, however we know little about the TEAD family of transcription factors that become activated by YAP1 and especially if they play a role during epiblast and primitive endoderm formation. Here we show that compaction occurs heterogeneously between the 8- and 16-cell stages. While 8-cell stage blastomeres are not yet polarized, polarized outer cells and non-polarized inner cells arise in compacted 16-cell stage embryos, however, they do not arise by symmetric and asymmetric divisions. While trophectoderm specifiers TEAD1, YAP1 and GATA3 mostly co-localise in the nuclei of polarized outer/trophectoderm cells, they are also found in some cells of compacting embryos before polarity is established indicating that differentiation into trophectoderm cells can be initiated independently of polarity. In the inner cell mass, TEAD1 and YAP1 also distinguish GATA4 positive cells in a salt-and-pepper distribution and in the sorted primitive endoderm cells. We suggest that TEAD1/YAP1 signalling plays a role both in the initiation of trophectoderm and the maintenance of primitive endoderm differentiation. Summary statement YAP1 and TEAD1 play a role both in the initiation of trophectoderm and the maintenance of primitive endoderm differentiation in human embryos