Reconstructing fate decisions in the peripheral sensory nervous system of the head
Lead Research Organisation:
King's College London
Department Name: Craniofacial Dev and Stem Cell Biology
Abstract
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Technical Summary
Unravelling the molecular control of developmental programmes remains a key question in development, stem cell biology and reprogramming. Recent advances in single cell transcriptomic and chromatin profiling have provided new avenues to address these questions establishing molecular catalogues of cells and characterising cell complexity. However, a key challenge remains to link transcriptional profiles directly to in vivo lineage decisions. Bringing together developmental and computational biology this project will tackle this challenge to investigate the molecular control of cell fate decisions in the cranial sensory nervous system. Specifically, we will
- Use single cell RNAseq to characterise how cell complexity emerges as sensory progenitors become committed to olfactory, eye, ear and sensory ganglia identity. This will also allow us to determine dynamic transcriptional changes;
- Use bulk and single cell ATACseq to identify changes in enhancer activity and use this information to predict upstream regulators and regulatory modules;
- Use CRISPR-based cell scarring to reconstruct cell lineage decisions; sampling scarred cells for scRNAseq allows us to link transcriptome information with fate choices in vivo;
- Integrate the above data to identify candidate fate determinants and test their function in vivo.
This project will establish the genetic hierarchy that controls how sensory progenitors diversify and acquire their unique cell identity. We will establish the in vivo lineage tree, clonal relationship of cells and explore multipotency or lineage restriction. Our data will not only provide new understanding of fundamental mechanisms in biology, but also form the basis for cell reprogramming as well as providing a rich resource for future exploration.
- Use single cell RNAseq to characterise how cell complexity emerges as sensory progenitors become committed to olfactory, eye, ear and sensory ganglia identity. This will also allow us to determine dynamic transcriptional changes;
- Use bulk and single cell ATACseq to identify changes in enhancer activity and use this information to predict upstream regulators and regulatory modules;
- Use CRISPR-based cell scarring to reconstruct cell lineage decisions; sampling scarred cells for scRNAseq allows us to link transcriptome information with fate choices in vivo;
- Integrate the above data to identify candidate fate determinants and test their function in vivo.
This project will establish the genetic hierarchy that controls how sensory progenitors diversify and acquire their unique cell identity. We will establish the in vivo lineage tree, clonal relationship of cells and explore multipotency or lineage restriction. Our data will not only provide new understanding of fundamental mechanisms in biology, but also form the basis for cell reprogramming as well as providing a rich resource for future exploration.
