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Project summary

Exploring the first week of embryonic development

Embryonic stem cells are cells isolated from the early embryo that have the potential to give rise to all the cell types found in an adult individual. Research on embryonic stem cells has made major advances over the past three decades, and the discovery that fully differentiated cells can be reprogrammed into early-stage stem cells has raised hopes for their future use.

 

Research on early embryonic development has largely relied on mice as a model system, while the human embryo remains relatively unexplored. This needs to change if pluripotent stem cells, which can give rise to all the cell types in an adult individual, are to be used safely and effectively in regenerative medicine, which aims to restore or replace damaged cells and tissues.

 

During the first few days after fertilisation, cells divide rapidly to generate the first three tissues, comprising two extraembryonic cell types and one embryonic cell type. Trophoblast cells will form the future placenta, while hypoblast cells will give rise to the future extraembryonic membranes. The third cell type consists of epiblast cells, which will form the future embryo. Embryonic stem cells are derived from these epiblast cells.

 

However, embryonic stem cells from mice and humans have been shown to differ substantially in their morphology, gene expression and culture requirements. The reasons for these differences have not yet been established. Human embryonic stem cells more closely resemble stem cells isolated from later-stage mouse embryos, known as epiblast-derived stem cells. This is just one indication of striking differences in how these cell types mature in mice and humans.

 

The overall aim of the research project is to expand our knowledge of the molecular and cellular mechanisms that govern early embryonic development and to apply this knowledge to early human developmental biology. The study has two specific fundamental objectives: to characterise how and when pluripotent stem cells become committed to particular cell types in the early embryo, and to characterise the two types of stem cells found during mouse development and determine whether both are also present in the human embryo.

 

These studies will not only increase our fundamental understanding of early human embryonic development, but may also have important implications for regenerative medicine and for understanding the underlying causes of early pregnancy complications and miscarriage.