Genome-wide analysis of Schwann cell gene expression in LKB1-SCKO mutant mice prior to occurrence of axon degeneration
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Jinsheng Yu
PROVIDER: E-GEOD-60325 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Analysis of gene expression in LKB1(Stk11)-depleted sciatic nerves (LKB1-SCKO) vs control nerves from age-matched mice. Gene expression profiles are predominantly derived from Schwann cell glia and provide important information about the response of peripheral nerve Schwann cells to inactivation of the metabolic regulator protein LKB1(aka Stk11).
2014-08-12 | GSE60325 | GEO
Project description:Wallerian degeneration (WD) involves the fragmentation of axonal segments disconnected from their cell bodies, segmentation of the myelin sheath, and removal of debris by Schwann cells and immune cells. The removal and downregulation of myelin-associated inhibitors of axonal regeneration and synthesis of growth factors by these two cell types are critical responses to successful nerve repair. Here, we analyzed the transcriptome of the sciatic nerve of mice carrying the Wallerian degeneration slow (WldS) mutant gene, a gene that confers axonal protection in the distal stump after injury, therefore causing significant delays in WD, neuroinflammation, and axonal regeneration. 56 C57BL6 mice and 56 C57BL/6 OlaHsd-Wlds mice were anesthetized with isoflurane and underwent a microcrush lesion of their left sciatic nerve at the mid-thigh level (exept naive mice, t0). At 0, 3, 7 and 14 days post-injury, mice were anesthetized and killed by cervical dislocation. Sciatic nerves were collected and conective tissue removed. A 4-mm long sciatic nerve segment was taken from the nerve distal stump, starting at 1 mm distal from the lesion up to 5 mm distal. Distal nerve stumps were pooled by group and RNA extracted. Samples were hybridized to GeneChip® Mouse Genome 430 2.0 Array (Affymetrix). Biological replicate was done.
2011-06-01 | E-GEOD-22291 | biostudies-arrayexpress
Project description:The aim of our study is to determine the functions of histone deacetylases (HDACs) 1 and 2 in Schwann cells during postnatal development of the peripheral nervous system (PNS). Schwann cells are the myelinating glial cells of the PNS. At birth, mouse sciatic nerves mature in 2 subsequent phases: 1/ big caliber axons get sorted into a 1 to 1 relationship with Schwann cells, 2/ Schwann cells build a myelin sheath around sorted axons. In mice where both HDAC1 & HDAC2 have been specifically knocked out in Schwann cells, both phases are impaired. HDACs are chromatin remodeling enzymes, they can thus alter gene expression directly. We want to identify which genes controlled by HDAC1 and HDAC2 in Schwann cells are necessary for the maturation of sciatic nerves. Because HDAC1 and HDAC2 can compensate for each other loss to some extend, we will first analyze changes of gene expression in HDAC1/HDAC2 double KO animals. We expect to gain critical insights into the molecular mechanisms controlling Schwann cell differentiation and myelination. This knowledge is of key importance for the success of regenerative medicine in peripheral neuropathies, nerve tumors, and transplantation paradigms in non-regenerative CNS lesions and in large PNS injuries. 3 double knockout mutants for HDAC1 and HDAC2 and 3 control littermates were analyzed. Tissues analyzed: sciatic nerves of 2 day-old mouse pups
2011-02-25 | E-GEOD-27451 | biostudies-arrayexpress
Project description:To investigate the potential function of lncRNAs in Schwann cell (SCs) response to sciatic nerve damage and repair, we extracted the total RNA of crushed sciatic nerves and intact contralateral nerves for RNA-sequencing (RNA-seq). A total of 98 differentially expressed lncRNAs (including 46 up-regulated and 52 down-regulated lncRNAs) and 77 differentially expressed mRNAs (including 55 up-regulated and 22 down-regulated mRNAs) were identified between crushed sciatic nerves and normal control (log 2 FC > 1 and p < 0.001).
2022-07-06 | GSE149657 | GEO
Project description:The regenerative capacity of peripheral nerves declines during aging, contributing to the development of neuropathies, limiting organism function. Changes in Schwann cells prompt failures in instructing maintenance and regeneration of aging nerves; altered inflammatory environment leading to a defective Schwann cell response, as an underlying mechanism of impaired nerve regeneration during aging. Chronic inflammation was detected in intact uninjured old nerves, characterized by increased macrophage infiltration and raised levels of monocyte chemoattractant protein 1 (MCP1) and CC chemokine ligand 11 (CCL11). Schwann cells in the old nerves appeared partially dedifferentiated, accompanied by an activated repair program independent of injury. Upon sciatic nerve injury, an initial delayed immune response was followed by a persistent hyperinflammatory state accompanied by a diminished repair process. As a contributing factor to nerve aging, we showed that CCL11 interfered with Schwann cell differentiation in vitro and in vivo. Our results indicate that increased infiltration of macrophages and inflammatory signals diminish regenerative capacity of aging nerves by altering Schwann cell behavior. The study identifies CCL11 as a promising target for anti‐inflammatory therapies aiming to improve nerve regeneration in old age.
2019-09-18 | GSE137504 | GEO
Project description:Ebf genes regulate differentiation of several cell type. Ebf2 is expressed in Schwann cells and Ebf2-/- mice show among other phenotypical abnormalities a delay in the onset of myelination associated to a decreased expression of genes regulating myelination. In addition at one month of age Ebf2-/- mice show decreased motor conduction velocity and morphological alteration in sciatic nerves. Ebf2 target genes are unknown. To identify Ebf2 target genes with a role in myelination, we compared the expression profiles of sciatic nerves isolated from P2 Wt and Ebf2-/- mice by microarray analysis. We used microarray to find Ebf2 candidate target genes by comparing gene expression of Ebf2-/- sciatic nerve and wt nerves 2 days postnatally (P2) a time point in which Ebf2-/- pups present a delay in the onset of myelination.
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Project description:To shed light on the early processes of immune response to peripheral nerve injury, we first used genome-wide transcriptional profiling and bioinformatics (Ingenuity, NextBio) pathway analyses of the proximal (P; regenerating) and distal (D; degenerating) nerve stumps at day 1 in the sciatic nerve axotomy model in rats. We identified a number of specific immunomodulatory genes and pathways that were regulated shortly post-injury in both the P and D segments, including all members of the interleukin (IL), chemokine, tumor necrosis factor (TNF), matrix metalloproteinase (MMP), toll-like receptor (TLR), tissue inhibitor of metalloproteinase (TIMP), ion channel and myosin families. Immunomodulatory calcium-binding S100A8 and S100A9 were the top up-regulated genes in both the D and P segments. In cultured Schwann cells stimulated with the purified S100A8/A9 heterodimer we recorded a high level of similarity of the activated genes and pathways with that of the injured nerve, especially in the activation of the chemokine and cytokine gene networks that support agranulocyte and granulocyte chemotaxis, adhesion, transmigration and rolling signaling pathways. We also confirmed activation of multiple cell death related gene networks supporting TNFR1, natural killer cell receptor and death receptor apoptosis signaling in the D stump, and the gluconeogenesis/glycolysis and cytoskeletal motility signaling in the P stump, corroborated by activation of ERK, PI3K and JNK kinase pathways. As compared to the D segment, multiple additional pathways were more efficiently upregulated in the P stump, including the IL-6 and -17, MMP-9, calcium, activated agranulocyte, leukocyte rolling and glutathione-mediated detoxification signaling pathways. These data suggest that shortly after nerve injury, upregulation of S100A8/A9 is responsible for the expression and release of chemokines and cytokines by Schwann cells, necessary to generate the initial chemotactic gradient and guide the hematogenous immune cells into the injury site. Gene expression profiling of total RNAs extracted from injured and non-injured rat sciatic nerves, and primary rat Schwann cells stimulated with S100A8/A9 proteins
2015-01-01 | E-GEOD-62282 | biostudies-arrayexpress
Project description:Schwann cell (Büngner) repair cells play a critical role in orchestrating nerve repair after injury, but the reprogramming process that generates them is poorly understood. We present the first combined whole genome coding and non-coding RNA and CpG methylation study after nerve injury. We show that genes involved in epithelial to mesenchymal transition are enriched in repair cells and we identify long non-coding RNAs in Schwann cells. We demonstrate that the AP-1 transcription factor c-Jun regulates the expression of certain micro RNAs in repair cells, in particular miR-21 and miR-34. Surprisingly, changes in CpG methylation are limited in injury, unlike development, and restricted to specific locations, such as enhancer regions of novel Schwann cell specific genes, such as Nedd4l, and near to local enrichment of AP-1 motifs. These epigenetic changes significantly broaden our understanding of Schwann cell reprogramming in peripheral nervous system tissue repair. To identify epigenetic regulators underlying successful nerve regeneration we generated RNA-Seq, small-RNA-Seq and whole genome bisulfite sequencing libraries for uninjured nerve versus three and/or seven day post nerve transection sciatic nerves of adult C57BL/6J mice crush.
2017-08-30 | E-MTAB-5633 | biostudies-arrayexpress
Project description:In order to uncover the biological processes affected in glial cells by aging, we analyzed microarray gene expression of the Schwann cell-rich mouse sciatic nerve at 17 time-points throughout life, from day of birth until senescence. In addition, we combined these data with the microarray gene expression data of myelin 56 day-old mouse mutants carrying deletions of either Pmp22, SCAP or Lpin1. Seven mice were dissected per developmental or aging time-point. Both sciatic nerves were isolated from each mouse and tissues were pooled per time-point to extract total RNA. For the mutants and their wild-type littermates, sciatic nerves were dissected from three mice per genotype. Tissues were not pooled, which generated triplicates per genotype. Total RNA was extracted, purified and quality-controlled. For each condition, 300 ng of total RNA was used to synthesize cRNA using the Illumina TotalPrep RNA amplification kit (Ambion). The cRNA was then quantified, quality controlled and hybridized to the MouseWG-6 v1 expression Beadchips (Illumina) according to the manufacturerM-^Rs instructions.
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Project description:The aim of our study is to determine the functions of histone deacetylases (HDACs) 1 and 2 in Schwann cells during postnatal development of the peripheral nervous system (PNS). Schwann cells are the myelinating glial cells of the PNS. At birth, mouse sciatic nerves mature in 2 subsequent phases: 1/ big caliber axons get sorted into a 1 to 1 relationship with Schwann cells, 2/ Schwann cells build a myelin sheath around sorted axons. In mice where both HDAC1 & HDAC2 have been specifically knocked out in Schwann cells, both phases are impaired. HDACs are chromatin remodeling enzymes, they can thus alter gene expression directly. We want to identify which genes controlled by HDAC1 and HDAC2 in Schwann cells are necessary for the maturation of sciatic nerves. Because HDAC1 and HDAC2 can compensate for each other loss to some extend, we will first analyze changes of gene expression in HDAC1/HDAC2 double KO animals. We expect to gain critical insights into the molecular mechanisms controlling Schwann cell differentiation and myelination. This knowledge is of key importance for the success of regenerative medicine in peripheral neuropathies, nerve tumors, and transplantation paradigms in non-regenerative CNS lesions and in large PNS injuries.
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