Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Diversified transcriptional responses of myeloid and glial cells in spinal cord injury shaped by HDAC3 activity

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE153737 | GEO | 2021/01/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Spinal cord injury (RNA sequencing data)

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

Microglia and macrophages promote corralling, wound compaction and recovery in spinal cord injury via Plexin-B2

Project description:Tissue repair after spinal cord injury (SCI) requires mobilization of immune and glial cells to form a protective barrier that seals the wound and facilitates debris clearing, inflammatory containment, and matrix compaction. This process involves corralling, wherein phagocytic immune cells become confined to the necrotic core surrounded by an astrocytic border. Here, we elucidate a temporally distinct gene signature in injury-activated microglia/macrophages (IAM), which engages axon guidance pathways. Plexin-B2 is upregulated in IAM, which is required for motosensory recovery after SCI. Plexin-B2 deletion in myeloid cells impairs corralling, leading to diffuse tissue damage, inflammatory spillover, and hampered axon regeneration. Corralling begins early and requires Plexin-B2 in both microglia and macrophages. Mechanistically, Plexin-B2 promotes microglia motility, steers IAM away from colliding cells, and facilitates matrix compaction. Our data thus establish Plexin-B2 as an important link that integrates biochemical cues and physical interactions of IAM with the injury microenvironment during wound healing.

2019-12-23 | GSE113566 | GEO

Differential Response Following Spinal Cord Injury in EphA4 Knockout

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

Defining the microglia transcriptome during disease progression in ALS transgenic mice

Project description:Purpose: We purified spinal cord microglia utilizing percoll gradients and magnetic beads, followed by transcriptome profiling (RNA-seq) to define microglia expression profiles against other neural, immune cell-types. We next observed how the microglial transcriptomes change during activation in the SOD1-G93A mouse model of motor neuron degeneration at 3 time points. We also compared these profiles with that induced by LPS injection. Results and conclusions: ALS microglia were found to differ substantially from those activated by LPS and from M1/M2 macrophages by comparison with published datasets. These ALS microglia showing substantial induction of a neurodegeneration-tailored phenotype, with induction of lysosomal, RNA splicing, and Alzheimer's disease pathway genes. Overall they express a mixture of neuroprotective and neurotoxic factors during activation in ALS mice, showing that neuro-immune activation in the spinal cord is a double-edged sword. We also detected the transcriptional nature of surface marker expression in microglia (CD11b, CD86, CD11c), and substantial T-cell microglia cross-talk using correlative microglia transcriptome/FACS analysis. 42 total RNA samples from purified spinal cord microglia were subjected to paired-end RNA-sequencing. Parallel flow cytometry data was collected from the same spinal cords.

2013-07-15 | E-GEOD-43366 | biostudies-arrayexpress

Differential Response Following Spinal Cord Injury in EphA4 Knockout

2012-05-24 | GSE34430 | GEO

Location of Neonatal Microglia Drives Small Extracellular Vesicles Content and Biological Functions

Project description:Combining proteomics and systems biology analyses, we demonstrated that neonatal microglial cells derived from two different CNS locations (cortex and spinal cord) displayed different phenotypes upon different physiological or pathological conditions. These cells also exhibited great variability in terms of both cellular and small extracellular vesicles (sEVs) protein contents and levels. Bioinformatics data analysis showed that the cortical microglia had anti-inflammatory and neurogenesis/tumorigenesis properties, while the spinal cord microglia was rather involved in inflammatory response process. Of interest, while both sEVs microglia sources enhanced growth of DRGs axons, only the spinal cord-derived sEVs microglia under LPS stimulation significantly attenuated glioma proliferation. These results were confirmed through neurite outgrowth assays in DRGs cell line and glioma proliferation analysis in 3D spheroid cultures. Results from these in vitro assays indicated that the microglia localized at different CNS regions can ensure different biological functions. Together, these works indicate that neonatal microglia locations regulate their physiological and pathological functional fates, and could explain the high prevalence of brain vs. spinal cord glioma in adults.

2020-05-26 | PXD016093 | Pride

Modifying macrophages at the periphery has the capacity to change microglial reactivity and increase ALS survival

Project description:Microglia and peripheral macrophages, combined, have been implicated in the motor neuron disease Amyotrophic Lateral Sclerosis (ALS), but without discriminating their respective roles. We now show that macrophages along peripheral motor neuron axons of ALS mice and patients react to neurodegeneration. In ALS mice, peripheral myeloid cell infiltration into the spinal cord was limited and disease duration dependent. Targeted gene modulation of the reactive oxygen species pathway in peripheral myeloid cells of ALS mice, using cell replacement, reduced both peripheral macrophage and microglial activation, delayed symptoms and increased ALS mouse survival. Transcriptomics revealed that sciatic nerve macrophages and microglia reacted very different to neurodegeneration, with abrupt temporal changes in macrophages and progressive, unidirectional activation in microglia. Modifying peripheral macrophages suppressed proinflammatory microglial responses, with a strong shift towards neuronal support. Thus, modifying macrophages at the periphery has the capacity to influence disease progression and is of therapeutic value for ALS.

2020-10-19 | GSE156202 | GEO

Spinal cord injury (RNA sequencing data)

2014-12-03 | GSE62698 | GEO

Early Involvement of Peripherally Derived Monocytes in Inflammation in an NMO-Like Mouse Model [Monocytes]

Project description:Neuromyelitis optica (NMO) is an autoimmune inflammatory disease that primarily affects the spinal cord and optic nerves in the central nervous system (CNS). It is characterized by the presence of immunoglobulin G (IgG) antibodies against aquaporin 4, a protein found in astrocytes (known as NMO-IgG). Monocytes/macrophages and microglia accumulate at the active injury sites and contribute to the disease process. However, it is unclear whether these active cells originate from circulating monocytes/macrophages or resident microglia. Recent studies have investigated the role of microglia/macrophages in multiple sclerosis (MS) using specific microglial markers, such as P2ry12 and Tmem119, and have shown that active cells are derived from microglia. In contrast, the function of monocyte/macrophages and microglia in NMO has not been extensively studied. Therefore, this study aims to analyze the functions of monocytes/macrophages and microglia using microglial markers (P2ry12 and Tmem119) in an NMO-like mouse model and evaluate their role in the pathophysiology of NMO.

2024-01-17 | GSE235277 | GEO

Early Involvement of Peripherally Derived Monocytes in Inflammation in an NMO-Like Mouse Model [microglia]

2024-01-17 | GSE235276 | GEO