Generating a global view of cell lineage trees during early mouse embryo development (360G-Wellcome-215920_Z_19_Z)

Understanding the routes through which a single cell populates the adult organism is one of the most fundamental yet elusive areas of biology. This project aims to use recent innovations in single-cell technology to generate a blueprint of cell fate decisions during early mouse development, and to examine the mechanisms behind the regulative nature of embryogenesis. Firstly, CRISPR-Cas9 technology will be employed to induce thousands of unique barcodes in cells, enabling the interrogation of cellular clonal history. Secondly, lineage tracing analysis will be combined with single-cell RNA sequencing which will provide the molecular resolution to precisely classify cell types and build up a fate map of early development. These data will be used to answer fundamental, outstanding questions in developmental biology. Finally, these analyses will be performed in chimeric embryos which contain cells unable to contribute to certain lineages to analyse compensatory behaviour. This will shed light on the largely unexplored area of the plasticity of cell fate decisions and the molecular control behind them. Together these analyses will generate a detailed, publicly-available chart of the clonal history and expression profiles of every cell during gastrulation and thereby provide an important reference point toward understanding a wealth of cellular processes.