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Whole-genome gene expression profiling of dorsal root ganglion neurons after nerve damage

ABSTRACT: We generated whole-genome gene expression profiles of dorsal root ganglion (DRG) neurons following nerve damage. DRG neurons extend one peripheral axon into the spinal nerve and one central axon into the dorsal root. The peripheral axon regenerates vigorously, while in contrast the central axon has little regenerative capacity. For this study, two groups of animals were subjected either to sciatic nerve (SN) or dorsal root (DR) crush, and at 12, 24, 72 hours and 7 days after the crush, lumbar DRGs L4, L5 and L6 were dissected and total RNA was extracted. For each time point after lesion, three biological replicate RNA samples were hybridized together with the common reference sample consisting of labeld RNA pooled from three unlesioned animals.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Harold MacGillavry

PROVIDER: E-GEOD-21007 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Whole-genome gene expression profiling of dorsal root ganglion neurons after nerve damage

Project description:We generated whole-genome gene expression profiles of dorsal root ganglion (DRG) neurons following nerve damage. DRG neurons extend one peripheral axon into the spinal nerve and one central axon into the dorsal root. The peripheral axon regenerates vigorously, while in contrast the central axon has little regenerative capacity. For this study, two groups of animals were subjected either to sciatic nerve (SN) or dorsal root (DR) crush, and at 12, 24, 72 hours and 7 days after the crush, lumbar DRGs L4, L5 and L6 were dissected and total RNA was extracted.

2010-09-01 | GSE21007 | GEO

Robust axonal regeneration occurs in the injured CAST/Ei mouse central nervous system

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2015-07-22 | E-GEOD-67130 | biostudies-arrayexpress

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2018-08-06 | GSE105442 | GEO

Self-renewing macrophages in dorsal root ganglia contribute to promote nerve regeneration

Project description:Primary sensory neurons with cell soma in dorsal root ganglia (DRG) project axons in both the peripheral nervous system and the spinal cord. Whereas the peripheral axon can regenerate after injury, the central axon cannot, providing an opportunity to identify the mechanisms that promote axon regeneration. Using this system, multiple intrinsic mechanisms operating in sensory neurons have been shown to promote axon regeneration. Peripheral sensory neurons also benefit from a supportive environment. In particular, macrophages play important roles in nerve regeneration by clearing debris and regulating Schwann cell function at the site of injury in the nerve. Nerve macrophages have been characterized at the molecular level and derive for the most part from infiltrating monocytes. However, the role and origin of macrophages in the DRG remains poorly understood. Following a 14-days treatment with a CSF1R inhibitor, less than 10% of macrophages remained in the DRG. Recovery from this treatment resulted in a dramatic macrophage repopulation, with the number of DRG macrophages reaching level similar to untreated mice three days post injury. These repopulated DRG macrophages contribute to promote axon regeneration. Our scRNA-seq analysis allow in-depth characterization of the repopulated DRG macrophages in response to nerve injury. These data will provide a better understanding of DRG macrophages and the molecular mechanisms by which they contribute to peripheral nerve repair. These studies may lead to new potential targets to promote axon regeneration.

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Project description:The goal of this study was to compare the transcriptional effects of sciatic nerve injury and spinal cord injury on lumbar dorsal root ganglion (DRG) and FACS-sorted dorsal column (DC) sensory neurons. We performed RNA-seq of whole DRG from naïve and spinal cord-injured (SCI) mice (1dpi) and compared this with previously published data for sciatic nerve transection. In order to assess changes specifically in DC neurons, we performed RNA-seq from FACS-sorted DC neurons from Thy1-YFP16 transgenic mice in naïve, sciatic nerve injured (SNI), and SCI (1 and 3dpi). We found that DC neurons alter their transcriptome after SCI, but that gene changes after SCI mostly differ from SNI. These transcriptional differences may reflect both growth promoting and growth inhibitory effects on axon regeneration after SCI.

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Translational Regulation in Initial Stages of the Neuronal Injury Response

Project description:Transcriptional events leading to outgrowth of neuronal axons have been intensively studied, but the role of translational regulation in this process is not well understood. Here we use translatome analyses by ribosome pull-down and protein synthesis characterization by metabolic isotopic labeling to study nerve injury and axon outgrowth proteomes in rodent dorsal root ganglia (DRG) and sensory neurons. We identify over 1600 gene products that are primarily translationally regulated in DRG neurons after nerve injury, many of which contain a 5’UTR CERT motif, implicating the translation initiation factor Eif4e in the injury response. We further identified approximately 200 proteins that undergo robust de novo synthesis in the initial stages of axon growth. ApoE is one of the highly synthesized proteins in neurons, and inhibition of its signaling affects axon outgrowth. These findings suggest prominent roles for translational regulation in initial stages of the neuronal injury response and axon extension.

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Transcriptional Profiling of Dorsal Root Ganglion Neurons Following Sciatic Nerve Injury

Project description:To elucidate transcriptional responses in peripherally injured neurons, we performed RNA-seq of dorsal root gangliona (DRG) sensory neurons at 1 and 5 days following sciatic nerve injury.

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Axon-enriched lincRNA ALAE is required for axon elongation via regulating local mRNA translation

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MicroRNA profiling in dorsal root ganglion after sciatic nerve injury

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