Early mammalian embryogenesis is controlled by mechanisms governing the balance between pluripotency and differentiation.
We have found that the expression of early lineage-specific genes can vary significantly between species (Chen et al., 2009; Niakan and Eggan, 2013) with implications for developmental control and stem cell derivation. However, the mechanisms involved in patterning the human embryo are still unclear.
We seek to further elucidate key molecular and cellular properties of human pre-implantation embryos and compare these with early mouse development. Towards this aim, we are characterising the gene expression patterns throughout human preimplantation development. We will use this information to modulate conditions for in vitro establishment of alternative stem cells from human embryos, with the aim of expanding the repertoire of clinically relevant cells.
A major aim of this work is derivation of human extra-embryonic stem cells, which will have importance for modeling placental related failures of pregnancy and the earliest stages of embryogenesis. These early cell fate decisions are fundamental for human life and have clinical importance for the derivation and use of stem cells.
Are embryonic differentiation mechanisms conserved between mice and humans? In mice, the caudal-related homeodomain transcription factor, Cdx2 is expressed prior to blastocyst formation. By contrast, here we see that human embryos initiate CDX2 expression later, once the blastocyst is formed, and have persistent co-localisation of CDX2 and the octamer-binding transcription factor OCT4 in the trophectoderm, suggesting significant differences in the initiation and restriction of lineage defining transcription factors.