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Global views of cell type specification and differentiation

Project description

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.

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.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-ADG - Advanced Grant

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Call for proposal

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(opens in new window) ERC-2018-ADG

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Host institution

UNIVERSITAT BASEL
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 411 440,00
Address
PETERSPLATZ 1
4051 Basel
Switzerland

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Region
Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 411 440,00

Beneficiaries (1)

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