Study: Mouse retinal ganglion cell adult atlas and optic nerve crush time series 112345 cells

Single-cell profiles of retinal neurons differing in resilience to injury reveal neuroprotective genes

Single-cell RNA-sequencing (10x genomics) of adult mouse retinal ganglion cells before and at six time points after optic nerve crush. 

GEO: GSE137400

Contact: Karthik Shekhar at karthik@broadinstitute.org  or Nicholas Tran at ntran@g.harvard.edu

Citation: Tran NM*, Shekhar K*, Whitney IE*, Jacobi A*, Benhar I, Hong G, Yan W, Adiconis X, Arnold ME, Lee JM, Levin JZ, Lin D, Wang C, Lieber CM, Regev A, He Z, Sanes JR. 'Single-Cell Profiles of Retinal Ganglion Cells Differing in Resilience to Injury Reveal Neuroprotective

Genes', Neuron (2019), https://doi.org/10.1016/j.neuron.2019.11.006  Link to study: https://www.cell.com/neuron/fulltext/S0896-6273(19)30969-9

Abstract: Neuronal types in the central nervous system differ dramatically in their resilience to injury or insults. Here we studied the selective resilience of mouse retinal ganglion cells (RGCs) following optic nerve crush (ONC), which severs their axons and leads to death of ~80% of RGCs within 2 weeks. To identify expression programs associated with differential resilience, we first used single-cell RNA-seq (scRNA-seq) to generate a comprehensive molecular atlas of 46 RGC types in adult retina. We then tracked their survival after ONC, characterized transcriptomic, physiological, and morphological changes that preceded degeneration, and identified genes selectively expressed by each type. Finally, using loss- and gain-of-function assays in vivo, we showed that manipulating some of these genes improved neuronal survival and axon regeneration following ONC. This study provides a systematic framework for parsing type-specific responses to injury, and demonstrates that differential gene expression can be used to reveal molecular targets for intervention.