Mechanisms of lineage commitment during exit from pluripotency in vivo (360G-Wellcome-203813_Z_16_A)

In early mammalian development, a pool of cells in the embryo can generate all cell types of the body, an ability referred to as 'pluripotency'. Specification of the cells is regulated by selective activation of genes that define tissue identities. These developmental programs are regulated by proteins known as 'transcription factors' that direct expression of other genes. However, the precise mechanisms that control cell fate specification are still poorly understood. The aim of my project is to understand the molecular mechanism of how genetically identical cells can be instructed to differentiate. I will focus on understanding the functional role of covalent 'epigenetic' DNA modifications in cell lineage priming and specification. To be able to address this fundamental question, I will use mouse embryos and stem cell culture systems, linked to imaging and single cell technologies to study the effect of perturbation of DNA modifications on cell fate specification. The results from my project will help us to understand how cells regulate their fate in early development. This is of great importance to understand developmental defects and learn how to instruct stem cells in culture for differentiation for potential use in cellular therapies in regenerative medicine.