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Single-cell profiles of retinal neurons differing in resilience to injury reveal neuroprotective genes

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE137400 | GEO | 2019/11/27

REPOSITORIES: GEO

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

Project description: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.

| S-EPMC6923571 | biostudies-literature

Single-cell profiles of retinal neurons differing in resilience to injury reveal neuroprotective genes - Atlas of adult mouse retinal ganglion cells

Project description:Neuronal types in the central nervous system differ dramatically in their resilience to injury or insults. Here we studied selective resilience in mouse retinal ganglion cells (RGCs) following optic nerve crush (ONC), which severs their axons and leads to death of ~80% of RGCs in 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 45 RGC types in adult retina. We tracked their survival after ONC, characterized transcriptomic, morphological, and physiological changes that preceded degeneration, and identified genes selectively expressed by each type. Finally, loss- and gain-of-function assays in vivo 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 these responses can be used to reveal molecular targets for intervention.

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Single-cell profiles of retinal neurons differing in resilience to injury reveal neuroprotective genes - Adult control RGCs treated with Actinomycin

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Single-cell profiles of retinal neurons differing in resilience to injury reveal neuroprotective genes - Atlas of adult mouse retinal ganglion cells [Smart-seq2]

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Single-cell profiles of retinal neurons differing in resilience to injury reveal neuroprotective genes

Project description:Single-cell profiles of retinal neurons differing in resilience to injury reveal neuroprotective genes

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Single-cell profiles of retinal neurons differing in resilience to injury reveal neuroprotective genes - Time course of transcriptomic changes in single retinal ganglion cells following optic nerve crush

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Single-cell profiles of retinal neurons differing in resilience to injury reveal neuroprotective genes - Atlas of adult mouse retinal ganglion cells

Project description:Single-cell profiles of retinal neurons differing in resilience to injury reveal neuroprotective genes - Atlas of adult mouse retinal ganglion cells

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Single-cell profiles of retinal neurons differing in resilience to injury reveal neuroprotective genes - Adult control RGCs treated with Actinomycin

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Single-cell profiles of retinal neurons differing in resilience to injury reveal neuroprotective genes - Atlas of adult mouse retinal ganglion cells [Smart-seq2]

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