Spinal cord injury (RNA sequencing data)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE62698 | GEO | 2014/12/03
SECONDARY ACCESSION(S): PRJNA264835
REPOSITORIES: GEO
Similar Datasets
Project description:We investigated the gene expression profile of monocyte-derived macrophages and microglia following spinal cord injury. Moreover, we investigated the gene expression profole of M-CSF induced macrophages and new-born derived microglia following TGFb1 treatment. monocyte-derived macrophages and microglia following spinal cord injury M-CSF induced macrophages and new-born derived microglia following TGFb1 treatment
2014-12-03 | E-GEOD-62698 | biostudies-arrayexpress
Project description:Traumatic spinal cord injury (SCI) triggers a neuro-inflammatory response dominated by tissue-resident microglia and monocyte derived macrophages (MDMs). Since activated microglia and MDMs are morphologically identical and express similar phenotypic markers in vivo, identifying injury responses specifically coordinated by microglia has historically been challenging. Here, we pharmacologically depleted microglia and use anatomical, histopathological, tract tracing, bulk and single cell RNA sequencing to reveal the cellular and molecular responses to SCI controlled by microglia. We show that microglia are vital for SCI recovery and coordinate injury responses in CNS-resident glia and infiltrating leukocytes. Depleting microglia exacerbates tissue damage and worsens functional recovery. Conversely, restoring select microglia-dependent signaling axes, identified through sequencing data, in microglia depleted mice prevents secondary damage and promotes recovery. Additional bioinformatics analyses reveal that optimal repair after SCI and likely other forms of neurological disease, might be achieved by co-opting key ligand-receptor interactions between microglia, astrocytes and MDMs.
2022-06-01 | GSE196928 | GEO
Project description:Mice lacking the developmental axon guidance molecule EphA4 have previously been shown to exhibit extensive axonal regeneration and functional recovery following spinal cord injury. To assess mechanisms by which EphA4 may modify the response to neural injury, a microarray was performed on spinal cord tissue from mice with spinal cord injury and sham injured controls. RNA was purified from spinal cords of adult EphA4 knockout and wild-type mice four days following lumbar spinal cord hemisection or laminectomy only and was hybridised to Affymetrix All-Exon Array 1.0 GeneChips. While subsequent analyses indicated that several pathways were altered in EphA4 knockout mice, of particular interest was the attenuated or otherwise altered expression of a number of inflammatory genes, including Arginase 1, expression of which was lower in injured EphA4 knockout compared to wild-type mice. Immunohistological analyses of different cellular components of the immune response were then performed in injured EphA4 knockout and wild-type spinal cords. While numbers of infiltrating CD3+ T cells were low in the hemisection model, a robust CD11b+ macrophage / microglial response was observed post-injury. There was no difference in the overall number or spread of macrophages / activated microglia in injured EphA4 knockout compared to wild-type spinal cords at two, four or fourteen days post-injury, however a lower proportion of Arginase-1 immunoreactive macrophages / activated microglia was observed in EphA4 knockout spinal cords at four days post-injury. Subtle alterations in the neuroinflammatory response in injured EphA4 knockout spinal cords may contribute to the regeneration and recovery observed in these mice following injury. Comparison was made between gene expression in wild-type and knockout samples both before and after injury. 3 replicates per group.
2012-05-23 | E-GEOD-34430 | biostudies-arrayexpress
Project description:Microglia are resident myeloid cells of the central nervous system (CNS). Recently, single-cell RNA sequencing (scRNAseq) has enabled description of a disease-associated subtype of microglia (DAM) with a role in neurodegeneration and demyelination. In this study we use scRNAseq to investigate the temporal dynamics of immune cells harvested from the epicenter of traumatic spinal cord injury (SCI). As a consequence of SCI, homeostatic microglia undergo permanent transcriptional re-programming into a subtype of microglia with striking similarities to previoysly reported DAM as well as a distinct microglial state found during development. Using a microglia depletion model we showed that DAM in SCI are derived from homeostatic microglia and strongly enhance recovery of hind limb locomotor function following injury.
2021-12-24 | GSE142849 | GEO
Project description:Mice lacking the developmental axon guidance molecule EphA4 have previously been shown to exhibit extensive axonal regeneration and functional recovery following spinal cord injury. To assess mechanisms by which EphA4 may modify the response to neural injury, a microarray was performed on spinal cord tissue from mice with spinal cord injury and sham injured controls. RNA was purified from spinal cords of adult EphA4 knockout and wild-type mice four days following lumbar spinal cord hemisection or laminectomy only and was hybridised to Affymetrix All-Exon Array 1.0 GeneChips. While subsequent analyses indicated that several pathways were altered in EphA4 knockout mice, of particular interest was the attenuated or otherwise altered expression of a number of inflammatory genes, including Arginase 1, expression of which was lower in injured EphA4 knockout compared to wild-type mice. Immunohistological analyses of different cellular components of the immune response were then performed in injured EphA4 knockout and wild-type spinal cords. While numbers of infiltrating CD3+ T cells were low in the hemisection model, a robust CD11b+ macrophage / microglial response was observed post-injury. There was no difference in the overall number or spread of macrophages / activated microglia in injured EphA4 knockout compared to wild-type spinal cords at two, four or fourteen days post-injury, however a lower proportion of Arginase-1 immunoreactive macrophages / activated microglia was observed in EphA4 knockout spinal cords at four days post-injury. Subtle alterations in the neuroinflammatory response in injured EphA4 knockout spinal cords may contribute to the regeneration and recovery observed in these mice following injury.
2012-05-24 | GSE34430 | GEO
Project description:Microglia are considered both pathogenic and protective during recovery from demyelination, but their precise role remains ill-defined. Here, using an inhibitor of colony stimulating factor 1 receptor (CSF1R), PLX5622, and mice infected with a neurotropic coronavirus (mouse hepatitis virus, strain JHMV), we show that depletion of microglia after clearance of virus infection resulted in impaired myelin repair and prolonged clinical disease. Microglia were required only during the early stages of remyelination. Notably, large deposits of extracellular vesiculated myelin and cellular debris were detected in the spinal cords of PLX5622-treated and not control mice, which correlated with decreased numbers of oligodendrocytes in demyelinating lesions in drug-treated mice. Further, gene expression analyses demonstrated differential expression of genes involved in myelin debris clearance, lipid and cholesterol recycling, and promotion of oligodendrocyte function. The results also demonstrate that microglial function could not be compensated by infiltrating macrophages. Together, these results demonstrate key roles for microglia in debris clearance and the initiation of remyelination following infection with a neurotropic coronavirus but are not necessary during later stages of remyelination.
2020-02-07 | GSE144911 | GEO
Project description:Transcriptome analysis of spinal cord microglia and total spinal cord from Lewis rats intratracheally treated with PBS, neomycin or vancomycin.
2021-12-21 | GSE192411 | GEO
Project description:The innate immunity influences neural repair after spinal cord injury (SCI). Here, we combined myeloid-specific nuclear transcriptomics and single-cell RNA-sequencing to uncover a common core but also temporally distinct gene programs in injury-activated microglia and macrophages (IAM). Intriguingly, we detected a wide range of microglial activation states even in healthy spinal cord; upon injury, reactive microglia and infiltrated macrophages progressively acquired an overall reparative, yet highly diversified gene expression profile, while maintaining their distinct transcriptional identities. Microglia and macrophages each comprise four distinct transcriptional subtypes with specialized tasks. Notably, IAM and disease-associated microglia (DAM) shared similar gene signatures, with a predominant enrichment in infiltrating macrophages and only a small subset of reactive microglia that specialized in phagocytosis, autophagy, and TyroBP network activity. We also identified an immediate response microglial subtype that may serve as source population for microglial transformation, and a highly proliferative subtype that is controlled by the epigenetic regulator HDAC3. Together, our data unveiled diversification of myeloid and other glial cell types and an extensive influence of HDAC3, which may be exploited to enhance neural repair.
2021-01-27 | GSE153737 | GEO
Project description:RNA-seq analysis of microglia following spinal cord injury demonstrated that microglia response is driven by time after injury but not lesion severity.
2017-03-27 | GSE96055 | GEO
Project description:The inflammatory response after spinal cord injury (SCI) is an important contributor to secondary damage. Infiltrating macrophages can acquire a spectrum of activation states, however, the microenvironment at the SCI site favors macrophage polarization into a pro-inflammatory phenotype, which is one of the reasons why macrophage transplantation has failed. In this study, we investigated the therapeutic potential of the macrophage secretome for SCI recovery. We investigated the effect of the secretome in vitro using peripheral and CNS-derived neurons and human neural stem cells. Moreover, we perform a pre-clinical trial using a SCI compression mice model and analyzed the recovery of motor, sensory and autonomic functions. Instead of transplanting the cells, we injected the paracrine factors and extracellular vesicles that they secrete, avoiding the loss of the phenotype of the transplanted cells due to local environmental cues. We demonstrated that different macrophage phenotypes have a distinct effect on neuronal growth and survival, namely, the alternative activation with IL-10 and TGF-β1 (M(IL-10+TGF-β1)) promotes significant axonal regeneration. We also observed that systemic injection of soluble factors and extracellular vesicles derived from M(IL-10+TGF-β1) macrophages promotes significant functional recovery after compressive SCI and leads to higher survival of spinal cord neurons. Additionally, the M(IL-10+TGF-β1) secretome supported the recovery of bladder function and decreased microglial activation, astrogliosis and fibrotic scar in the spinal cord. Proteomic analysis of the M(IL-10+TGF-β1)-derived secretome identified clusters of proteins involved in axon extension, dendritic spine maintenance, cell polarity establishment, and regulation of astrocytic activation. Overall, our results demonstrated that macrophages-derived soluble factors and extracellular vesicles might be a promising therapy for SCI with possible clinical applications.
2024-02-14 | PXD048453 | Pride