Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell RNA-seq in monozygotic twins discordant for multiple sclerosis

ABSTRACT: Here we investigated the earliest possible evidence of subclinical neuro-inflammation (SCNI) using a small cohort of monozygotic twins where one sibling had clinically definite MS and the other been clinically "healthy" but has a maximal genetic for developing MS. In contrast to subjects with radiologically isolated syndrome (RIS), our group of very early SCNI does not even fulfill the (arbitrary) MRI criteria for RIS but have more subtle MRI changes and/or evidence of neuro-inflammation in the CSF, e.g. oligoclonal bands (OCBs). For analyzing CSF samples from Twin pairs and controls in greater detail we applied single-cell whole transcriptome sequencing (scRNAseq). Our findings demonstrate that even the earliest experimentally approachable stage of MS is characterized by synergistic activation of CD8+ T cells, CD4+ T cells and B cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE127969 | GEO | 2019/08/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Global transcriptome profiling in peripheral blood mononuclear cells identifies dysregulation of immune processes in individuals with radiologically isolated syndrome

Project description:The presence of brain/spinal white matter lesions typical for multiple sclerosis (MS) in asymptomatic individuals is known as ‘radiologically isolated syndrome’ (RIS). Allow for the established fact that RIS patients are at high risk of MS development, understanding the causes underlying RIS onset and the variability of its conversion to MS are of great importance. In order to investigate RIS-specific transcription signature we perfromed high-throughput RNA sequencing in peripheral blood mononuclear cells (PBMCs) of 8 RIS patients and 8 age- and sex-matched healthy controls. We identified 57 differentially expressed genes (DEGs), which levels differed by more than 2 times when compared these groups (FDR p value < 0.05). Gene ontology enrichment analysis in the "biological process" category revealed 16 signalling pathways significantly overrepresented by identified DEGs. The most significant changes in gene expression in PBMCs of RIS patients occur in pathways involved in regulation of the immune response, cytokine and chemokine signaling, cytokine production, and leukocyte migration. In general, analyzing the global transcriptome we demonstrated the dysregulation of immune processes in PBMCs of RIS patients, confirming the current assumption that RIS represents the preclinical stage and/or subclinical form of MS.

2021-11-02 | GSE186895 | GEO

Transcription profiling of human naive CD4+ T cells from CIS early manifestation multiple sclerosis samples, case-control, time-series study

Project description:Clinically isolated syndrome (CIS) refers to the earliest clinical manifestation of multiple sclerosis (MS). Currently there are no prognostic biological markers that accurately predict conversion of CIS to clinically definite MS (CDMS). Furthermore, the earliest molecular events in MS are still unknown. We used microarrays to study gene expression in naÃ¯ve CD4+ T cells from 37 CIS patients at time of diagnosis and after one year. Supervised machine-learning methods were used to build predictive models of disease conversion. We identified 975 genes whose expression segregated CIS patients into 4 distinct subgroups. A subset of 108 genes further discriminated patients from one of these (group#1) from other CIS patients. Remarkably, 92% of patients from group #1 converted to CDMS within 9 months. Consistent downregulation of TOB1, a critical regulator of cell proliferation, was characteristic of group #1 patients. Decreased TOB1 expression at the RNA and protein levels was also confirmed in experimental autoimmune encephalomyelitis (EAE). Finally, a genetic association was observed between TOB1 variation and MS progression in an independent cohort. These results indicate that CIS patients at high risk of conversion have impaired regulation of T cell quiescence resulting in earlier activation of pathogenic CD4+ cells. Experiment Overall Design: Expression data was taken from 37 CIS patients and 28 healthy controls at baseline. 34 CIS patients and 10 healthy controls were resampled at a second time point, approximately one year later. Patients were followed clinically for up to two years to determine the TTC (time to conversion to MS)

2009-01-13 | E-GEOD-13732 | biostudies-arrayexpress

Characterizing cerebrospinal fluid immunity in neurological manifestations of COVID-19

Project description:Patients suffering from Coronavirus disease 2019 (COVID-19) can develop neurological sequelae, such as headache, neuroinflammatory or cerebrovascular disease. These conditions - here termed Neuro-COVID - are more frequent in patients with severe COVID-19. To understand the etiology of these neurological sequelae, we utilized single-cell sequencing and examined the immune cell profiles from the cerebrospinal fluid (CSF) of Neuro-COVID patients compared to patients with non-inflammatory and autoimmune neurological diseases or with viral encephalitis. The CSF of Neuro-COVID patients exhibited an expansion of dedifferentiated monocytes and of exhausted CD4+ T cells. Neuro-COVID CSF leukocytes featured an enriched interferon signature; however, this was less pronounced than in viral encephalitis. Repertoire analysis revealed broad clonal T cell expansion and curtailed interferon response in severe compared to mild Neuro-COVID patients. Collectively, our findings document the CSF immune compartment in Neuro-COVID patients and suggest compromised antiviral responses in this setting.

2020-12-11 | GSE163005 | GEO

CIS (multiple sclerosis) (case-control) (time-series)

Project description:Clinically isolated syndrome (CIS) refers to the earliest clinical manifestation of multiple sclerosis (MS). Currently there are no prognostic biological markers that accurately predict conversion of CIS to clinically definite MS (CDMS). Furthermore, the earliest molecular events in MS are still unknown. We used microarrays to study gene expression in naïve CD4+ T cells from 37 CIS patients at time of diagnosis and after one year. Supervised machine-learning methods were used to build predictive models of disease conversion. We identified 975 genes whose expression segregated CIS patients into 4 distinct subgroups. A subset of 108 genes further discriminated patients from one of these (group#1) from other CIS patients. Remarkably, 92% of patients from group #1 converted to CDMS within 9 months. Consistent downregulation of TOB1, a critical regulator of cell proliferation, was characteristic of group #1 patients. Decreased TOB1 expression at the RNA and protein levels was also confirmed in experimental autoimmune encephalomyelitis (EAE). Finally, a genetic association was observed between TOB1 variation and MS progression in an independent cohort. These results indicate that CIS patients at high risk of conversion have impaired regulation of T cell quiescence resulting in earlier activation of pathogenic CD4+ cells. Keywords: Disease state: CIS (Clinically Isolated Syndrome - Multiple Sclerosis) versus control. Time series: some patients and controls were resampled approximately one year later

2008-11-26 | GSE13732 | GEO

CSF B cells in relapsing multiple sclerosis are driven towards an antigen-experienced, inflammatory fate

Project description:Central nervous system B cells have several potential roles in multiple sclerosis (MS): secretors of proinflammatory cytokines and chemokines, presenters of autoantigens to T cells, producers of pathogenic antibodies, and reservoirs for viruses that trigger demyelination. To interrogate these roles, single-cell RNA sequencing (scRNA-Seq) was performed on paired cerebrospinal fluid (CSF) and blood from subjects with relapsing-remitting MS (RRMS; n = 12), other neurologic diseases (ONDs; n = 1), and healthy controls (HCs; n = 3). Single-cell immunoglobulin sequencing (scIg-Seq) was performed on a subset of these subjects and additional RRMS (n = 4), clinically isolated syndrome (n = 2), and OND (n = 2) subjects. Further, paired CSF and blood B cell subsets (RRMS; n = 7) were isolated using fluorescence activated cell sorting for bulk RNA sequencing (RNA-Seq). Independent analyses across technologies demonstrated that nuclear factor kappa B (NF-?B) and cholesterol biosynthesis pathways were activated, and specific cytokine and chemokine receptors were up-regulated in CSF memory B cells. Further, SMAD/TGF-ß1 signaling was down-regulated in CSF plasmablasts/plasma cells. Clonally expanded, somatically hypermutated IgM+ and IgG1+ CSF B cells were associated with inflammation, blood–brain barrier breakdown, and intrathecal Ig synthesis. While we identified memory B cells and plasmablast/plasma cells with highly similar Ig heavy-chain sequences across MS subjects, similarities were also identified with ONDs and HCs. No viral transcripts, including from Epstein–Barr virus, were detected. Our findings support the hypothesis that in MS, CSF B cells are driven to an inflammatory and clonally expanded memory and plasmablast/plasma cell phenotype.

2020-08-31 | GSE133028 | GEO

Transcription profiling of stroke-susceptible and asymptomatic human carotid plaques

Project description:A microarray analysis of advanced human atherosclerotic carotid artery plaques (equal or over 70% stenosis, NASCET criteria) from radiologically confirmed ipsilateral stroke patients (stroke-susceptible plaques, n=12) compared with carotid plaques collected from clinically asymptomatic patients with clear brain imaging (asymptomatic plaques, n=9) with equivalent conventional risk factors and severity of carotid stenosis.

2011-12-30 | E-MEXP-2257 | biostudies-arrayexpress

Project description:Microbiome of CSF from MS patients

| PRJNA354641 | ENA

CSF CD4+ T cells in MS

Project description:CSF CD4+ T cells in MS

| PRJNA721683 | ENA

Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis

Project description:Cerebrospinal fluid (CSF) protects the central nervous system (CNS) and analyzing CSF aids the diagnosis of CNS diseases, but our understanding of CSF leukocytes remains superficial. Here, using single cell transcriptomics, we identified a specific border-associated composition and transcriptome of CSF leukocytes. Multiple sclerosis (MS) – an autoimmune disease of the CNS – increased transcriptional diversity in blood, but increased cell type diversity in CSF including a higher abundance of cytotoxic phenotype T helper cells. A new analytical approach, named cell set enrichment analysis (CSEA) identified a cluster-independent increase of follicular T helper (TFH) cells potentially driving the known expansion of B lineage cells in the CSF in MS. In mice, TFH cells accordingly promoted B cell infiltration into the CNS and the severity of MS animal models. Immune mechanisms in MS are thus highly compartmentalized and indicate ongoing local T/B cell interaction.

2019-12-10 | GSE138266 | GEO

scRNAseq of blood and CSF CD4+ T cells from MS patients and controls

Project description:To study the regulation of candidate genes from our study in human cells, we analyzed CD4+ T cells from blood and CSF of MA patients and age and sex matched idiopathic intracranial hypertension controls We analyzed 40845 cells in control blood, 807 cells in control CSF, 29749 cells in MS blood and 15768 cells in MS CSF

2023-08-01 | GSE232343 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data