Project description:The failure of multiple sclerosis lesions to resolve in the months after they form leads to smouldering demyelination and axon degeneration (chronic active/slowly expanding lesions). To define mechanisms underlying this disabling, progressive neurodegenerative state, and to foster development of new therapeutics, we used MRI-informed single-nucleus RNA sequencing to profile the edge of demyelinated white matter lesions at various stages of inflammation and compared with healthy control white matter.
2021-09-01 | GSE180759 | GEO
Project description:Single-nucleus RNA sequencing of human cortex affected by multiple sclerosis
| PRJNA544731 | ENA
Project description:Single-nucleus RNA sequencing of human cerebellum and spinal cord samples from control individuals and patients with multiple sclerosis lesions
Project description:Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with marked heterogeneity in several aspects including pathological processes. Four histopathological patterns of MS have been described. Pattern II is characterized by infiltrating macrophages and T-cells and by antibody and complement deposition. Transcriptome analysis of three patern II demyelinating brain lesions from a multiple sclerosis patient using RNA sequencing demonstrated the presence of mRNA transcripts for genes specific of activated macrophages, T and B cells as well as genes coding for immunoglobulins, complement proteins and some pattern II associated proteins, providing additional evidence supporting pattern II demyelination. Examination of 3 different demyelinating lesions identified by Immunohistopathology.
Project description:In a previous study performed in our laboratory, the level of FGF1 RNA was found to be increased in remyelinated multiple sclerosis lesions compared to control brain (unpublished observation). Astrocytes play a key role in multiple sclerosis lesion formation. To shed light on potential FGF1-mediated functions in multiple sclerosis, the impact of FGF1 on astrocytes was investigated.
Project description:Due to commonalities in pathophysiology, age-related macular degeneration represents a uniquely accessible model to investigate therapies for neurodegenerative diseases, leading us to examine whether pathways of disease progression are shared across neurodegenerative conditions. Here we use single-nucleus RNA sequencing to profile lesions from 17 retinas with age-related macular degeneration and controls. We create a machine learning pipeline based on recent advances in data geometry and topology and identify activated glial populations enriched in the early phase of disease. Examining single-cell data from Alzheimer’s disease and progressive multiple sclerosis with our pipeline, we find a similar glial activation profile enriched in the early phase of these neurodegenerative diseases. In late-stage age-related macular degeneration, we identify a microglia-to-astrocyte signaling axis mediated by interleukin-1beta which drives angiogenesis characteristic of disease pathogenesis. Thus, due to shared glial states, the retina provides a system for investigating therapeutic approaches in neurodegenerative diseases.
Project description:In the present study we addressed several questions related to the mechanisms of cortical injury. We analyzed genome wide gene expression by microarrays, comparing active multiple sclerosis lesions with highly inflammatory lesions of chronic tuberculous meningitis, with neurodegenerative lesions of Alzheimer’s disease and with normal cortex of age matched controls. To clarify which inflammatory mediators drive demyelination in the human cortex, we characterized and compared the gene expression profile of cortices derived from patients with progressive Multiple Sclerosis (pMS), Meningitis tuberculosis (MT), Alzheimers disease (AD) as well as of normal cortex from age matched controls. 3 cases of each disease were included into the study. Preceding the gene expression profiling all cases were characterized histologically and areas of interest were identified. RNA was isolated from those areas, amplified and hybridized to Agilent G4112F whole genome microarrays.
Project description:Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with marked heterogeneity in several aspects including pathological processes. Four histopathological patterns of MS have been described. Pattern II is characterized by infiltrating macrophages and T-cells and by antibody and complement deposition. Transcriptome analysis of three patern II demyelinating brain lesions from a multiple sclerosis patient using RNA sequencing demonstrated the presence of mRNA transcripts for genes specific of activated macrophages, T and B cells as well as genes coding for immunoglobulins, complement proteins and some pattern II associated proteins, providing additional evidence supporting pattern II demyelination.
Project description:We report the single cell RNA sequencing of mouse CD8+ T cells infiltrating VK12653 Multiple Myeloma lesions upon treatment with anti-CD137 agonists .