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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

Jun promotes axon regeneration by binding enhancer sites and dimerizing with Atf3

Project description:Axon regeneration is a necessary step toward functional recovery after spinal cord injury. The AP-1 transcription factor c-Jun has long been known to play an important role in directing the transcriptional response of Dorsal Root Ganglion (DRG) neurons to peripheral axotomy that results in successful axon regeneration. Here we performed ChIPseq for Jun in mouse DRG neurons after a sciatic nerve crush or sham surgery in order to measure the changes in Jun’s DNA binding in response to peripheral axotomy. We found that the majority of Jun’s injury-responsive changes in DNA binding occur at putative enhancer elements, rather than proximal to transcription start sites. We also used a series of single polypeptide chain tandem transcription factors to test the effects of different Jun-containing dimers on neurite outgrowth in cortical and hippocampal neurons. These experiments demonstrated that dimers composed of Jun and Atf3 promoted neurite outgrowth in rat CNS neurons. Our work provides new insight into the mechanisms underlying Jun’s role in axon regeneration.

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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Ascending dorsal column sensory neurons respond to spinal cord injury and downregulate genes related to lipid metabolism

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.

2018-04-25 | GSE102316 | GEO

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

Project description:Long intergenic noncoding RNAs (lincRNAs) are critical regulators involved in diverse biological processes. However, the roles and related mechanisms of lincRNAs in axon development are largely unknown. To seek the axon-enriched lincRNAs in DRG neurons, we performed high-throughput RNA-seq of cultured rat dorsal root ganglion (DRG) neurons at P0 to profile lincRNAs. Profiling of highly expressed lincRNAs in RNA-seq and their enrichment in the axon of DRG neurons. We report a previously unappreciated axon-enriched lincRNA regulating axon elongation, thus referred to as ALAE. ALAE functionally associates with KHSRP for preventing KHSRP binding on Gap43 mRNA, thereby maintaining GAP43 synthesis and facilitating axon elongation.

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MicroRNA profiling in dorsal root ganglion after sciatic nerve injury

Project description:Changes in microRNA (miRNA) expression in the mouse L4 and L5 dorsal root ganglion following unilateral sciatic nerve transection. The timepoint of 7 days post-axotomy was chosen to capture miRNA expression profiles at a time when the injured neurons were beginning to regenerate. Two condition experiment, paired control DRG vs axotomised DRG following unilateral sciatic nerve transection. 3 biological replicates, one replicate per array. Dye swap in Replicate 2.

2011-05-06 | E-GEOD-29096 | biostudies-arrayexpress

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