Descripción del proyecto
El destino de cada célula durante la embriogénesis
La pregunta fundamental de la biología del desarrollo es cómo el linaje de las células (genealogía) y su trayectoria (historia de la expresión génica) determinan su diferenciación y especificación. Los progresos recientes en la edición y la secuenciación genéticas creó una oportunidad de estudiar el proceso de desarrollo con una resolución monocelular. Este proyecto financiado con fondos europeos va a utilizar nuevos métodos para reconstruir el destino y la evolución de células individuales durante la embriogénesis. Esta visión global del desarrollo celular se generará utilizando como modelos la embriogénesis y la organogénesis del pez cebra. Se establecerán árboles de trayectoria a partir de datos de secuenciación del ARN de una sola célula, mientras que los árboles de linaje se generarán mediante la edición de genes para el marcaje de células. La combinación de estos datos proporcionará la primera vista global exhaustiva de los procesos que determinan el desarrollo de los vertebrados.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
Régimen de financiación
ERC-ADG - Advanced GrantInstitución de acogida
4051 Basel
Suiza