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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

ABSTRACT: 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

PROVIDER: PRJNA592201 | ENA |

REPOSITORIES: ENA

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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

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.

2019-11-27 | GSE137398 | GEO

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

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 - 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 - Adult control RGCs treated with Actinomycin

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Intercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cells

Project description:The neuronal cell death results in neurodegenerative diseases. The extracellular environment plays a critical role in regulating cell viability. In this study, we explore how intercellular communication contributes to the survival of retinal ganglion cells (RGCs) following the optic nerve crush (ONC). By performing single-cell RNA-seq on whole retinal cells, we observed transcriptomic responses in non-RGC retinal cells to the injury, with astrocytes and Müller glia having the most interactions with RGCs. By comparing the RGC subclasses showing distinct resilience cell death, we identified top 47 interactions that are stronger in the high-survival RGCs, likely representing neuroprotective interactions. We performed functional assays on one of the receptors, Mu-opioid receptor (Oprm1). Although Oprm1 is preferentially expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs), its neuroprotective effect could be transferred to multiple RGC subclasses by specific overexpressing Oprm1 in pan-RGCs. Our study provides an atlas of cell-cell interactions in both intact and post-ONC retina and an effective strategy to predict molecular mechanisms in neuroprotection, underlying the principal role played by extracellular environment in supporting neuron survival.

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Single nuclei RNA-seq analysis of control and Dnmt3a conditional knockout (cKO) of retinal ganglion cells at 2 days post optic nerve crush.

Project description:Dnmt3a deficiency in retinal ganglion cells promotes axon regeneration in an optic nerve crush mouse model. To investigate the role of Dnmt3a in axon regeneration, retinal ganglion cell nuclei were sorted from control and retinal ganglion cell-specific Dnmt3a knockout mice at 2 days post optic nerve crush and applied for single nuclei RNA-seq analysis by 10X Genomics technology.

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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 - Atlas of adult mouse retinal ganglion cells [Smart-seq2]

Project description: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 - Adult control RGCs treated with Actinomycin

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

| PRJNA573602 | ENA

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