Single-Cell Profiles of Retinal Ganglion Cells Differing in Resilience to Injury Reveal Neuroprotective Genes
Name
nihms-1543498.pdf
Description
Accepted version
Size
3.65 MB
Format
Adobe PDF
Checksum (MD5)
633cf4538bef5f2ba8575ea215385787
Author(s)
Tran, Nicholas M
Shekhar, Karthik
Whitney, Irene E
Jacobi, Anne
Benhar, Inbal
Hong, Guosong
Yan, Wenjun
Adiconis, Xian
Arnold, McKinzie E
Lee, Jung Min
Date Issued
2019
Journal
Neuron
Publisher
Elsevier BV
Version
Author's final manuscript
Abstract
© 2019 Elsevier Inc. Neuronal types in the central nervous system differ dramatically in their resilience to injury or other 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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.NEURON.2019.11.006
