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 |
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Rok vydání: | 2019 |
Předmět: |
Male
Retinal Ganglion Cells 0301 basic medicine Cell Survival Nerve Crush Central nervous system Biology Bioinformatics Neuroprotection Retinal ganglion Article Transcriptome Mice 03 medical and health sciences 0302 clinical medicine Text mining Gene expression medicine Animals Axon Gene Retina business.industry General Neuroscience Nerve Regeneration medicine.anatomical_structure 030104 developmental biology Optic nerve Female sense organs business Neuroscience 030217 neurology & neurosurgery |
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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