Self-Organising Capacity of Stem Cells during Implantation and Early Post-Implantation Development: Implications for Human Development
|Title||Self-Organising Capacity of Stem Cells during Implantation and Early Post-Implantation Development: Implications for Human Development|
|Sponsor||European Research Council - Advanced Grant (ERC-AdG)|
|Institution||University of Cambridge|
Associated cell lines
Embryonic development progresses through successive cell fate decisions and intricate three-dimensional morphogenetic transformations. Implantation is the defining event in mammalian pregnancy when the body axes are established and the embryonic germ layers created. Despite its importance, a comprehensive understanding of the molecular mechanisms, transcriptional pathways, cellular interactions, as well as the spatiotemporal development of the embryo at implantation stages is at present lacking, due to the embryo’s small size and inaccessibility. To overcome these limitations, we generated a culture system that allows the development of implanting embryos outside of the mother. Such system provides the opportunity to address how architectural features and signalling events integrate to induce the emergence of the body plan. Combining this new technology with the analysis of genetically engineered mouse embryos, as well as human embryos, the aim of this research proposal is to fill the knowledge gap between pre and post-implantation development. Single cell sequencing, two-photon microscopy, high-content forward genetic screen and modelling will be merged with functional assessment of embryo development in vivo to characterize the determinants of implantation and early post-implantation development. This characterization will be further employed to explore the extent to which embryonic stem cells can recapitulate embryonic development, with tremendous potential for regenerative medicine. Knowledge of the cellular and molecular mechanisms that intertwine lineage specification, developmental potential and tissue morphogenesis will offer novel insight on the pathological causes of embryo lethality and congenital disorders. The proposed studies will shed light on this crucial yet mysterious stage of development in the mouse and offer outstanding potential to advance our understanding of development of the human embryo.