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Gene expression in adult sciatic nerves upon miRNA ablation and crush injury

ABSTRACT: We report RNA sequencing data from induced Schwann cell specific knockouts for DICER and DGCR8 as well as crush injured wild type animals. Induced deletion of DICER and DGCR8 results in expression of numerous injury response genes suggesting a requirement of those proteins in maintaining the myelinated Schwann cell fate.

ORGANISM(S): Mus musculus

PROVIDER: GSE109074 | GEO | 2018/10/08

REPOSITORIES: GEO

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Transcriptome analyses of miRNA pathway mutants and injury response in developing and adult sciatic nerves

Project description:We addressed the requirement of DGCR8, DROSHA and DICER functions in developing and adult Schwann cells (SCs) using mouse mutants. We found that the microprocessor components DGCR8 and DROSHA are crucial for axonal radial sorting and to establish correct SC numbers upon myelination. Transcriptome analysis revealed that the microprocessor is essential to prevent aberrant accumulation and de novo expression of injury-response genes. Those genes are predicted targets of stage-specifically enriched miRNAs. In agreement, DGCR8 and DICER are required for proper maintenance of the myelinated SC state. We conclude that the miRNA pathway is crucial for preventing inappropriate activity of injury response genes in developing and adult SCs.

2018-10-08 | GSE109075 | GEO

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Project description:In this study, we analyzed the transcriptome profiles of mouse sciatic nerves subjected to crush injuries after inducible deletion of Raptor conditionally in Schwann cells (using a PLPCreERT2-driven recombination of floxed alleles) as compared to controls (floxed Raptor homozygous, PLPCreERT2-negative). The transcriptome profiles of the contralateral uninjured nerves were also analyzed. Differentially expressed genes, defined as genes with a fold change>1.2 and fold discovery rate <0.05, in injured and contralateral nerves of mutants compared to controls were subjected to gene ontology analysis. Additionally, differentially expressed genes in injured mutants nerves as compared to injured control nerves were further analyzed for enrichment of transcription factor binding motifs in the corresponding promoter regions using the bioinformatic tool Homer version 4.9 (Heinz et al., Molecular Cell, 2010)

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Gene expression in adult sciatic nerves upon miRNA ablation and crush injury

Project description:Gene expression in adult sciatic nerves upon miRNA ablation and crush injury

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RNA expression in mutants of the miRNA pathway during myelination

Project description:RNA sequencing was performed comparing sciatic nerves of Schwann cell specific DICER mutants with SC-specific DGCR8 and DROSHA mutants.

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RNA expression in P1 sciatic nerves

Project description:RNA seq was performed comparing SC-specific Dicer mutants with SC-specific Lin28B transgenics to obtain an unbiased list of potentially de-regulated miRNA target candidates.

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DLK-gated responses in motoneurons following sciatic nerve crush

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Gene Expression in Mutant P0 Cre Dicer Mouse Sciatic Nerves

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Regional Gene Expression in the Retina, Optic Nerve Head, and Optic Nerve of Mice with Optic Nerve Crush and Experimental Glaucoma

Project description:A major risk factor for glaucomatous optic neuropathy is the level of intraocular pressure (IOP), which can lead to retinal ganglion cell axon injury and cell death. The optic nerve has a rostral unmyelinated portion at the optic nerve head followed by a caudal myelinated region. The unmyelinated region is differentially susceptible to IOP-induced damage in rodent models and in human glaucoma. While several studies have analyzed gene expression changes in the mouse optic nerve following optic nerve injury, few were designed to consider the regional gene expression differences that exist between these distinct areas. We performed bulk RNA-sequencing on the retina and on separately micro-dissected unmyelinated and myelinated optic nerve regions from naïve C57BL/6 mice, mice after optic nerve crush, and mice with microbead-induced experimental glaucoma (total = 36). Gene expression patterns in the naïve unmyelinated optic nerve showed significant enrichment of the Wnt, Hippo, PI3K-Akt, and transforming growth factor β pathways, as well as extracellular matrix–receptor and cell membrane signaling pathways, compared to the myelinated optic nerve and retina. Gene expression changes induced by both injuries were more extensive in the myelinated optic nerve than the unmyelinated region, and greater after nerve crush than glaucoma. Changes present three and fourteen days after injury largely subsided by six weeks. Gene markers of reactive astrocytes did not consistently differ between injury states. Overall, the transcriptomic phenotype of the mouse unmyelinated optic nerve was significantly different from immediately adjacent tissues, likely dominated by expression in astrocytes, whose junctional complexes are inherently important in responding to IOP elevation.

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Expression data of sciatic nerves from mice with Schwann-cell specific Sip1 deletion compared to control mice.

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