Totipotency versus fate in human embryonic stem cells (FWOAL722)

Human preimplantation development starts with the fusion of two highly differentiated cells - oocyte and sperm- resulting in a totipotent zygote. Totipotency refers to the ability of a single blastomere to have full developmental potential. During the first five days of embryogenesis, the zygote divides and changes morphologically and develops into a blastocyst in which the appearance of trophectoderm (TE) and inner cell mass (ICM) represents the first differentiation in human development. The ICM forms the embryo proper and can give rise to human embryonic stem cells (hESC). The TE is a differentiated epithelium responsible for implantation. At this moment, the study of human embryogenesis and our understanding of the underlying regulatory mechanisms are limited due to the scarcity of the human research materials and the ethical objections regarding the use of human embryos. In the mouse, lineage segregation is controlled by specific transcription factors and there are several models to explain how the TE and ICM lineages are established. The first lineage segregation occurs just before blastulation at the moment of compaction when cells flatten out, become adherent and generate an inner and outer population. It is still unclear how and when the first differentiation event happens in the human. In this developmental study we aim to examine the mechanisms initiating this fundamental process in inner and outer cells of human preimplantation embryos at the moment of compaction and blastulation. This study will contribute to our basic knowledge on human embryogenesis and stem cell biology.

Keywords:reproductive genetics, andrology, clinical genetics, embryology, assisted reproductive technology

Disciplines:Andrology, Embryology, Clinical genetics and molecular diagnostics, Gynaecology and obstetrics, Molecular and cell biology, Genetics