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Broad rim lesions are a novel pathological / morphological and imaging biomarker for rapid disease progression in Multiple Sclerosis (part 2)

ABSTRACT: Broad rim lesions are a novel pathological / morphological and imaging biomarker for rapid disease progression in Multiple Sclerosis (part 2)

PROVIDER: PRJNA1185739 | ENA |

REPOSITORIES: ENA

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Broad rim lesions are a novel pathological / morphological and imaging biomarker for rapid disease progression in Multiple Sclerosis (part 2)

Project description:Current Multiple Sclerosis (MS) treatments reduce relapse activity but have limited impact on disease progression. Clinical trials targeting progression often fail due to insufficient understanding of its underlying mechanisms. This study analyzes a clinically well-characterized MS autopsy cohort comparing selected individuals with opposite disease trajectories of slow versus rapid progression by extensive unbiased histology and spatial transcriptomics. It unveils a novel lesion type marked by an extensive myeloid cell rim with cellular and transcriptional signatures of inflammation, enhanced antigen presentation and lymphocyte activation that is strongly linked to rapid progression. Validation through an independent TSPO-PET study confirms the association between lesions with a broad myeloid cell rim and disease progression. These findings offer crucial insights into the mechanisms behind MS progression, identifying broad rim lesions as a biomarker for rapid disease progression and potentially guiding patient selection for future therapeutic trials targeting CNS intrinsic inflammation.

2025-02-12 | GSE281805 | GEO

Broad rim lesions are a novel pathological / morphological and imaging biomarker for rapid disease progression in Multiple Sclerosis

Project description:Broad rim lesions are a novel pathological / morphological and imaging biomarker for rapid disease progression in Multiple Sclerosis

| PRJNA1185732 | ENA

Broad rim lesions are a novel pathological / morphologicaland imaging biomarker for rapid disease progression in Multiple Sclerosis (part 1)

2025-02-12 | GSE264094 | GEO

Broad rim lesions are a novel pathological / morphologicaland imaging biomarker for rapid disease progression in Multiple Sclerosis (part 1)

Project description:Broad rim lesions are a novel pathological / morphologicaland imaging biomarker for rapid disease progression in Multiple Sclerosis (part 1)

| PRJNA1100974 | ENA

Broad rim lesions are a novel pathological / morphological and imaging biomarker for rapid disease progression in Multiple Sclerosis

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-02-12 | GSE281807 | GEO

Malassezia responds to environmental pH signals through the conserved Rim/Pal pathway

Project description:During mammalian colonization and infection, microorganisms must be able to rapidly sense and adapt to changing environmental conditions including alterations in extracellular pH. The fungus-specific Rim/Pal signaling pathway is one process that supports microbial adaptation to alkaline pH. This cascading series of interacting proteins terminates in the proteolytic activation of the highly conserved Rim101/PacC protein, a transcription factor that mediates microbial responses that favor survival in neutral/alkaline pH growth conditions, including many mammalian tissues. We identified the putative Rim pathway proteins Rim101 and Rra1 in the human skin colonizing fungus Malassezia sympodialis. Targeted mutation of these proteins confirmed their role in M. sympodialis growth at higher pH. Additionally, comparative transcriptional analysis of the mutant strains compared to wild-type suggested mechanisms for fungal adaptation to alkaline conditions. These signaling proteins are required for optimal growth in a murine model of atopic dermatitis, a pathological condition associated with increased skin pH. Together these data elucidate both conserved and phylum-specific features of microbial adaptation to extracellular stresses.

2024-02-01 | GSE254653 | GEO

RNAseq of rim cells and retinal neuroepithelial cells of zebrafish optic cup at 18-20ss stage

Project description:This data set was generated with the aim to identify a comprehensive list of genes expressed in the rim cells and the RNE cells during zebrafish optic cup morphogenesis. GFP expressed under vsx2 locus was used as a reporter to isolate the rim cells (with low GFP expression) and retinal neuroepithelial cells (with high GFP expression).

2019-01-09 | GSE124779 | GEO

Super-resolution imaging reveals disrupted higher-order heterochromatin organization at early-stage carcinogenesis on pathological tissue

Project description:Super-resolution imaging reveals disrupted higher-order heterochromatin organization at early-stage carcinogenesis on pathological tissue

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Super-resolution imaging reveals disrupted higher-order heterochromatin organization at early-stage carcinogenesis on pathological tissue

Project description:Abnormal chromatin structure is one of the hallmarks in cancer and has long been used for cancer diagnosis, but the observed aberrant chromatin structures characteristic of cancer cells is limited to microscale features, largely due to due to the diffraction-limited resolution of conventional light microscopy. Recent advances in super-resolution microscopy overcome the technical limitations of conventional light microscopy and enable the in-situ visualization of the higher-order chromatin structure down to ~30 nm. Here we present PathSTORM, a variant of stochastic optical reconstruction microscopy (STORM) optimized for super-resolution imaging of densely packed higher-order chromatin organization at different epigenomic states on pathological tissue. We then apply this tool to characterize the structural alteration of higher-order heterochromatin, enriched with H3K9me3 and satellite repeats, at various stages of carcinogenesis in mouse models and human tissue specimens. PathSTORM reveals that a significant disruption of higher-order heterochromatin structure occurs in early carcinogenesis when tissue still appears histologically normal and becomes progressively severe during neoplastic progression. The disrupted higher-order heterochromatin structure also appears to be a common feature that reflects the evolution of carcinogenesis independent of molecular pathways in multiple tumor types. Taken together, PathSTORM can serve as a powerful tool to visualize higher-order chromatin structure in the spatial context of tissue architecture on pathological tissue. Our findings provide new insights on the role of higher-order heterochromatin structure in carcinogenesis, especially at the early stage, and have the potential for improving cancer diagnosis, risk stratification and facilitating the development and evaluation of new preventive strategies.

2020-03-19 | GSE121800 | GEO

MALDI-imaging-guided transcriptomics

Project description:MALDI-imaging-guided Transcriptomics

| PRJEB69276 | ENA