Project description DEENESFRITPL Individual cells' fate and destiny during embryogenesis The fundamental question of developmental biology is how cell lineage (pedigree) and trajectory (history of gene expression) determine its differentiation and specification. Recent progress in gene-editing and sequencing created an opportunity to study the developmental process at single-cell resolution. This EU-funded project is going to employ new methods to reconstruct individual cell fate and evolution during embryogenesis. This global view of cellular development will be generated using zebrafish embryogenesis and organogenesis as a model. Trajectory trees will be established from single-cell RNA sequencing data while lineage trees will be generated using gene-editing for cell marking. Combination of these data will provide the first comprehensive and global view of processes determining vertebrate development. Show the project objective Hide the project objective Objective Each cell in our body has a specific biography that is defined by its pedigree relationship with other cells (lineage) and by its history of gene expression (trajectory). A fundamental question in cellular and developmental biology has been how the lineage and trajectory of a cell lead to its specification and differentiation. Remarkable progress in genome editing and single-cell sequencing has generated the opportunity to understand this process at global scales and single-cell resolution. We have recently developed methods to reconstruct the cellular ancestry and transcriptional trajectories of cells during embryogenesis. The resulting lineage and trajectory trees can be analyzed to gain comprehensive views of how cellular diversity arises and how differentiation leads to physiologically specialized cell types. To generate such global views of cellular development, we will: 1. Define the cellular diversity and gene expression trajectories during zebrafish embryogenesis and organogenesis. Trajectory trees will be generated from scRNA-seq data and analyzed to reconstruct the gene expression pathways underlying fate specification. 2. Reveal the relationships between lineage and transcriptional trajectories during fate specification. Lineage trees will be generated by marking cells via genome editing and combined with trajectory trees to reveal the cellular paths towards fate specification. 3. Discover the gene expression cascades that remodel cells into physiologically functional types. Cell biological modules will be identified by comparing gene enrichment in differentiation trajectories and reveal the specialized and shared mechanisms of differentiation. These studies will help provide the first comprehensive and global view of the trajectories and lineages underlying vertebrate development. Our focus is on the zebrafish model system, but the data and concepts developed in this project will be applicable to other developmental and cellular systems. Fields of science medical and health sciencesmedical biotechnologygenetic engineeringgene therapyhumanitieshistory and archaeologyhistorynatural sciencesbiological sciencesdevelopmental biologynatural sciencesbiological sciencesgeneticsgenomes Keywords lineage developmental biology of the cell zebrafish Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2018-ADG - ERC Advanced Grant Call for proposal ERC-2018-ADG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Host institution UNIVERSITAT BASEL Net EU contribution € 2 411 440,00 Address PETERSPLATZ 1 4051 Basel Switzerland See on map Region Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 411 440,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNIVERSITAT BASEL Switzerland Net EU contribution € 2 411 440,00 Address PETERSPLATZ 1 4051 Basel See on map Region Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 411 440,00
