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ScRNAseq analysis of mouse L4 whole dorsal root ganglions following sciatic nerve cush, dorsal root crush and spinal cord injury

ABSTRACT: scRNAseq analysis of mouse L4 whole dorsal root ganglions following sciatic nerve cush, dorsal root crush and spinal cord injury

PROVIDER: PRJNA666909 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12762112_1.fastq.gz	Fastqsanger.gz
	SRR12762112_2.fastq.gz	Fastqsanger.gz
	SRR12762113_1.fastq.gz	Fastqsanger.gz
	SRR12762113_2.fastq.gz	Fastqsanger.gz
	SRR12762114_1.fastq.gz	Fastqsanger.gz

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scRNAseq analysis of mouse L4 whole dorsal root ganglions with and without sciatic nerve crush injury

Project description:scRNAseq analysis of mouse L4 whole dorsal root ganglions with and without sciatic nerve crush injury

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scRNAseq analysis of mouse L4 whole dorsal root ganglions with and without sciatic nerve crush injury

Project description:Peripheral sensory neurons with cell body in dorsal root ganglia (DRG) switch to a regenerative state after nerve injury to enable axon regeneration and functional recovery. Studies of nerve injury responses in sensory neurons have revealed signaling and transcriptional mechanisms that increase their intrinsic regenerative capacity. However, the extent to which satellite glial cells (SGC), which completely surround the neuronal soma contribute to these responses remains unexplored. Using single cell RNA-seq, we defined the transcriptional profile of SGC in naïve and injured conditions and identified Fabp7, also known as BLBP, as a novel marker of SGC. We report that nerve injury elicits gene expression changes in SGC, which are mostly related to lipid metabolism, specifically fatty acid synthesis and the peroxisome proliferator-activated receptor (PPAR) signaling. Conditional deletion of Fatty acid synthase (Fasn), the key enzyme in de novo fatty acid synthesis, specifically in SGC, impairs axon regeneration. Treatment with fenofibrate, a PPARa agonist, rescues the impaired regeneration, suggesting that PPRAa, which belongs to a family of lipid regulated transcription factors, functions downstream of fatty acid synthesis in SGC to promote axon regeneration. These results unravel fatty acid synthesis in SGC as a fundamental novel mechanism mediating axon regeneration in mature peripheral nerves.

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scRNAseq analysis of mouse L4 whole dorsal root ganglions following sciatic nerve cush, dorsal root crush and spinal cord injury

Project description:After an injury in the adult mammalian central nervous system, lesioned axons fail to regenerate. This failure to regenerate contrasts with the remarkable potential of axons to grow following an injury in the peripheral nervous system. Peripheral sensory neurons with cell soma in dorsal root ganglia (DRG) switch to a regenerative state after nerve injury to enable axon regeneration and functional recovery. Decades of research have focused on the signaling pathways elicited by injury in sensory neurons and in Schwann cells that insulate axons as central mechanisms regulating nerve repair. However, neuronal microenvironment is far more complex and is composed of multiple cell types including endothelial, immune and glial cells. Whether the microenvironment surrounding neuronal soma contribute to the poor regenerative outcomes following central injuries remains largely unexplored. To answer this question, we performed a single cell transcriptional profiling of the DRG neuronal microenvironment response to peripheral and central injuries. In dissecting the roles of the microenvironment contribution, we have focused on a poorly studied glia population of Satellite Glial Cells (SGC) surrounding the neuronal cell soma. Upon a peripheral injury, SGC contribute to axon regeneration via Fatty acid synthase (Fasn)-PPARα signaling pathway. Our analysis reveals that in response to central injuries, SGC do not activate the PPAR signaling pathway. However, induction of this pathway with fenofibrate, an FDA- approved PPARα agonist used for dyslipidemia treatment, rescued axon regeneration following an injury to the central nerves. Collectively, our results uncovered a previously unappreciated role of the neuronal microenvironment differential response in central and peripheral injuries.

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Project description:Sciatic nerve crush was performed on cohorts of 2-month and 24-month old animals. Resulting gene-expression data were generated from dorsal root ganglia 5 days after injury compared to naïve animals. Results show differences in intrinsic growth responses with normal aging. Total RNA taken from L4 and L5 dorsal root ganglia 5 days after injury 2-month and 24-month old animals at either day 0 or day 5 after sciatic nerve crush injury.

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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.

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

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