Surviving the crush

Autor: Anne Jacobi, McKinzie E. Arnold, Wenjun Yan, Zhigang He, Dingchang Lin, Aviv Regev, Charles M. Lieber, Guosong Hong, Chen Wang, Inbal Benhar, Karthik Shekhar, Joshua Z. Levin, Joshua R. Sanes, Nicholas M. Tran, Irene E. Whitney, Jung Min Lee, Xian Adiconis
Rok vydání: 2019
Předmět:
Zdroj: Neuron
PMC
ISSN: 1471-0048
1471-003X
Popis: © 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.
Databáze: OpenAIRE
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