Periodic Reporting for period 2 - CellularBiographies (Global views of cell type specification and differentiation)
Periodo di rendicontazione: 2021-07-01 al 2022-12-31
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. 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 have aimed to: 1. Define the cellular diversity and gene expression trajectories during zebrafish embryogenesis and organogenesis. 2. Reveal the relationships between lineage and transcriptional trajectories during fate specification. 3. Discover the gene expression cascades that remodel cells into physiologically functional types.
These studies will help provide the first comprehensive and global view of the trajectories and lineages underlying vertebrate development.
To generate such global views of cellular development, we have aimed to: 1. Define the cellular diversity and gene expression trajectories during zebrafish embryogenesis and organogenesis. 2. Reveal the relationships between lineage and transcriptional trajectories during fate specification. 3. Discover the gene expression cascades that remodel cells into physiologically functional types.
These studies will help provide the first comprehensive and global view of the trajectories and lineages underlying vertebrate development.
We have generated single-cell atlases and gene expression trajectories of the developing brain. These studies revealed hundreds of cell types and defined the changes as neurons are specified and differentiate. We have improved our lineage-tracing technology and constructed lineage trees for brain development. We comprehensively reconstructed the cellular processes during the differentiation of two secretory cell types in the embryo.
We have established new technologies to trace lineages, reveal where genes are expressed and define which regions of the genome become accessible when cells specialize. These approaches will help provide deeper insights than initially hoped for.