SCSC · The molecular diversity of regeneration in the zebrafish spinal cord

Because the mammalian nervous system exhibits a limited capacity for regeneration, spinal-cord injury causes permanent damage in humans. In contrast, zebrafish regenerate their spinal cords after damage. Understanding this process in zebrafish might one day suggest regenerative strategies for humans. This proposal therefore aims to elucidate the transcriptional processes that regulate regeneration in the zebrafish spinal cord. Although genome-wide expression profiling has revealed factors that promote spinal cord regeneration, microarray and bulk RNA-seq methods are unable to localize candidates to particular cell types. The molecular diversity of cell types that contribute to spinal cord regeneration thus has not been fully explored, and the cell type-specific roles of the signals that instruct the process remain unclear. The applicant will address this gap by performing single-nucleus RNA-seq on regenerating zebrafish spinal cord and analyzing the data to reveal cell types and cell type-specific gene expression changes. This goal entails three specific aims: 1) Establish a protocol for isolating nuclei from the zebrafish spinal cord. 2) Establish a molecular taxonomy of cell types in the regenerating spinal cord. 3) Characterize cell type-specific gene-expression changes in the regenerating spinal cord. The project will be completed in a laboratory that specializes in single-cell RNA-seq methods and neuroscience, providing exceptional training in the experimental and computational methods associated with high-throughput single-cell analysis and preparing the applicant for a career as an independent investigator. The host institute is moreover a leading research institute at the forefront of neuroscience and single-cell biology, with postdoctoral career support. The proposal will yield an atlas of the cell type-specific transcriptional changes that occur during regeneration, providing new insight and a novel resource for researchers in the field of regeneration.