Cell signalling pathways governing lineage decisions of human naive pluripotent stem cells

Title Cell signalling pathways governing lineage decisions of human naive pluripotent stem cells
Acronym CellDecide
Start date 2023-10-02
End date 2026-08-31
Sponsor BBSRC Research Grant
Institution University of Aberdeen

Associated cell lines

Project Description

Cells actively communicate with one another through a series of highly sophisticated streams of chemical communication which we collectively refer to as the signalling pathways. Activation or inhibition of these pathways throughout early development and life control many key biological processes including directing undifferentiated cells down specific paths to become more specialised. Moreover, it is now widely recognised that perbutation of these delicate signalling pathways forms the foundation of disease, cancer and infertility in humans. Our general understanding of the signalling pathways that underpin these processes requires further investigation to reveal potential therapeutic opportunities. Human naive pluripotent stem cells (both embryonic and induced pluripotent) retain an intrinsic and rather remarkable feature of differentiating into extraembryonic cells types, resembling trophoblast- and hypoblast-like cells. Therefore, they provide the ideal model to investigate these pathways in a 2D system. Since this discovery, efforts have been made to understand which signalling pathways are important for maintainence and differentiation of naive pluripotent cells. In this project, we aim to dicepher the molecular dialogue of human naive pluripotent stem cells to facilitate differentiation into both hypoblast- and trophoblast-like cells through a series of systematic and hypothesis-driven experiments. In the spotlight, we have a particular interested in the roles of WNT/BCAT and NODAL signalling. We also want to uncover previously uncharacterised and unique target genes that retain exclusivity to their respective signalling pathways when their activity is directly modulated (either activation or inhibition). A more in-depth understanding of these concepts will assist in designing new treatments targeting diseases which effectively hijack signalling pathways and improve fertility and IVF outcomes.