Farnesol brain transcriptomics in CNS inflammatory demyelination
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ABSTRACT:
PROVIDER: PRJNA976694 | ENA |
REPOSITORIES: ENA
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2023-09-11 | GSE233583 | GEO
Project description:Adoptive transfer of T cells from wild-type (WT) mice to IL-17A-/- mice or T cells from IL-17A-/- mice to Rag-/- mice induced CNS demyelination in infected mice. Adoptive T cell experiments suggest that both T cells and non-T cells expressing IL-17A contribute to HSV-IL-2-induced CNS demyelination with no difference in the severity of demyelination between the two groups of IL-17A producing cells. IL-6, IL-10, or TGFβ did not contribute to CNS demyelination in infected mice. Transcriptome analysis between IL-17A-/- brain and spinal cord of infected mice with and without T cell transfer from WT mice revealed that “neuron projection extension involved in neuron projection guidance” and “ensheathment of neurons” pathways were associated with CNS demyelination. Collectively, the results indicate the importance of IL-17A in CNS demyelination and the possible involvement of more than three of IL-17 receptors in CNS demyelination
2023-01-24 | GSE219020 | GEO
Project description:Multiple sclerosis is a disease of the central nervous system (CNS) that is characterized by inflammation and focal areas of demyelination, ultimately resulting in axonal degradation and neuronal death. Several lines of evidence point towards a role for microglia and other CNS-associated macrophages in disease initiation and progression, but exactly how lesion formation is triggered is currently unknown. Here, we characterized early changes in MS brains through transcriptomic analysis of normal appearing white matter (NAWM). We found that NAWM was already characterized by expression of inflammatory genes and that expression of genes associated with stress-response was increased, likely as a result of changes in the macrophage compartment. Single cell RNA sequencing analysis confirmed an early stress response in brain macrophages and identified specific macrophage subsets that associate with different stages of demyelinating lesions. These data provide insight into early changes in MS brains that may provide therapeutic targets in order to limit lesion development and demyelination.
2022-02-02 | GSE179427 | GEO
Project description:Demyelination is a hallmark of multiple sclerosis, leukoencephalopathies, cerebral vasculopathies and several neurodegenerative diseases. The cuprizone mouse model is widely used to simulate demyelination occurring in these diseases. Here, we present a high-resolution snRNA-seq analysis of gene expression changes across all brain cells in this model. We define signatures of prototypic responses to demyelination and remyelination for each cell type, including anti-stress, anti-oxidant-, metabolic-, hypoxia-, IFN-, and IL-33-driven responses, and validate them at the protein level and in IL-33R-deficient mice. We identify related transcription regulators underpinning these pathways, including STAT3, NF-κB, OLIG1 and MAFB. Furthermore, snRNA- seq data provide novel insights into how various brain cell types connect and interact, defining complex circuitries previously unknown to impact demyelination and remyelination. As an explicative example, perturbation of microglia caused by TREM2 deficiency impacts the oligodendrocyte responses to demyelination. Altogether, this study provides a rich resource for future studies investigating mechanisms underlying demyelination and remyelination.
2023-03-27 | GSE204755 | GEO
Project description:Demyelination is a hallmark of multiple sclerosis, leukoencephalopathies, cerebral vasculopathies and several neurodegenerative diseases. The cuprizone mouse model is widely used to simulate demyelination occurring in these diseases. Here, we present a high-resolution snRNA-seq analysis of gene expression changes across all brain cells in this model. We define signatures of prototypic responses to demyelination and remyelination for each cell type, including anti-stress, anti-oxidant-, metabolic-, hypoxia-, IFN-, and IL-33-driven responses, and validate them at the protein level and in IL-33R-deficient mice. We identify related transcription regulators underpinning these pathways, including STAT3, NF-κB, OLIG1 and MAFB. Furthermore, snRNA- seq data provide novel insights into how various brain cell types connect and interact, defining complex circuitries previously unknown to impact demyelination and remyelination. As an explicative example, perturbation of microglia caused by TREM2 deficiency impacts the oligodendrocyte responses to demyelination. Altogether, this study provides a rich resource for future studies investigating mechanisms underlying demyelination and remyelination.
2023-03-27 | GSE204769 | GEO
Project description:Transcriptomic atlas and interaction networks of brain cells in mouse CNS demyelination and remyelination
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Project description:Intracranial inoculation of the neuroadapted JHM strain of mouse hepatitis virus (JHMV) into susceptible strains of mice results in acute encephalomyelitis and chronic immune-mediated demyelination similar to the human demyelinating disease multiple sclerosis (MS). JHMV infection of transgenic mice in which expression of the neutrophil chemoattractant chemokine CXCL1 is under the control of a tetracycline-inducible promoter active within GFAP-positive cells results in sustained neutrophil infiltration in the central nervous system (CNS) that correlates with an increase in spinal cord demyelination. We used single cell RNA sequencing (scRNAseq) and flow cytometry to characterize molecular and cellular changes within the CNS associated with increased demyelination in transgenic mice compared to control animals. These approaches revealed the presence of activated neutrophils as determined by increased expression of mRNA transcripts associated with increased neutrophil effector functions, such as CD63, MMP9, S100a8, S100a9, and ASPRV1, as well as by altered neutrophil morphology and protein expression. Collectively, these findings reveal insight into changes in the profile of neutrophils associated with increased white matter damage in mice persistently infected with a neurotropic coronavirus.
2022-09-09 | GSE212852 | GEO
Project description:Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination and axonal loss. Demyelinating lesions are associated with infiltrating T lymphocytes, bone marrow-derived macrophages (BMDM), and activated resident microglia. Tissue damage is thought to be mediated by T cell produced cytokines and chemokines, which activate microglia and/or BMDM to both strip myelin and produce toxic factors, ultimately damaging axons and promoting disability. However, the relative contributions of BMDM and microglia to demyelinating pathology are unclear, as their identification in MS tissue is difficult due to similar morphology and indistinguishable surface markers when activated. The CD4 T cell-induced autoimmune murine model of MS, experimental autoimmune encephalitis (EAE), in which BMDM are essential for demyelination, has revealed pathogenic and repair-promoting phenotypes associated with BMDM and microglia, respectively. Using a murine model of demyelination induced by a gliatropic coronavirus, in which BMDM are redundant for demyelination, we herein characterize gene expression profiles of BMDM versus microglia associated with demyelination. While gene expression in CNS infiltrating BMDM was upregulated early following infection and subsequently sustained, microglia expressed a more dynamic gene profile with extensive mRNA upregulation coinciding with peak demyelination after viral control. This delayed microglia response comprised a highly pro-inflammatory and phagocytic profile. Furthermore, while BMDM exhibited a mixed phenotype of M1 and M2 markers, microglia repressed the vast majority of M2-markers. Overall, these data support a pro-inflammatory and pathogenic role of microglia temporally remote from viral control, whereas BMDM retained their gene expression profile independent of the changing environment. As demyelination is caused by multifactorial insults, our results highlight the plasticity of microglia in responding to distinct inflammatory settings, which may be relevant for MS pathogenesis.
2022-10-02 | GSE214472 | GEO
Project description:Transcriptomic atlas and interaction networks of brain cells in mouse CNS demyelination and remyelination [B6]
| PRJNA842096 | ENA
Project description:Transcriptomic atlas and interaction networks of brain cells in mouse CNS demyelination and remyelination [Trem2KO]
| PRJNA842235 | ENA