Single-Cell Profiles of Retinal Ganglion Cells Differing in Resilience to Injury Reveal Neuroprotective Genes

Nicholas M. Tran, Karthik Shekhar, Irene E. Whitney, Anne Jacobi, Inbal Benhar, Guosong Hong, Wenjun Yan, Xian Adiconis, McKinzie E. Arnold, Jung Min Lee, Joshua Z. Levin, Dingchang Lin, Chen Wang, Charles M. Lieber, Aviv Regev, Zhigang He, Joshua R. Sanes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

363 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1039-1055.e12
JournalNeuron
Volume104
Issue number6
DOIs
StatePublished - 18 Dec 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.

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