Single-cell profiles of retinal neurons differing in resilience to injury reveal neuroprotective genes
| Autor: | Inbal Benhar, Dingchang Lin, Chen Wang, Joshua R. Sanes, McKinzie E. Arnold, Irene E. Whitney, Guosong Hong, Aviv Regev, Wenjun Yan, Charles M. Lieber, Zhigang He, Nicholas M. Tran, Xian Adiconis, Karthik Shekhar, Joshua Z. Levin, Jung Min Lee, Anne Jacobi |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Retina Central nervous system Retinal Biology Retinal ganglion Neuroprotection Transcriptome 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine.anatomical_structure chemistry medicine Optic nerve sense organs Axon Neuroscience 030217 neurology & neurosurgery 030304 developmental biology |
| DOI: | 10.1101/711762 |
| Popis: | SummaryNeuronal 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. |
| Databáze: | OpenAIRE |
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