Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-nucleus RNA sequencing analysis of normal-appearing brains from RRMS and SPMS patients

ABSTRACT: snRNA-seq reveals that normal-appearing brain regions from RRMS and SPMS patients have divergent cell type-specific gene expression profiles, with clinical ramifications for approved sphingosine 1-phosphate (S1P) receptor modulators.

ORGANISM(S): Homo sapiens

PROVIDER: GSE179590 | GEO | 2022/01/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Single-nucleus RNA sequencing analysis of normal-appearing brains from RRMS and SPMS patients

Project description:Single-nucleus RNA sequencing analysis of normal-appearing brains from RRMS and SPMS patients

| PRJNA744238 | ENA

Whole blood RNA-seq data of SPMS vs RRMS patients from paper titled \"Relapsing remitting and secondary progressive multiple sclerosis are characterised by distinct metabolomic and transcriptomic signatures that could aid patient management strategies\\

Project description:We combined analysis of serum metabolomics and whole blood transcriptomics in patients with RRMS and SPMS to build an integrated network describing these different phases of MS and to help improve our understanding of the potential mechanisms driving disease progression. Transcriptomic analysis of whole blood was performed to assess differential gene expression between five patients with RRMS and eight patients with SPMS.

2024-09-19 | E-MTAB-13378 | biostudies-arrayexpress

Novel Biomarkers and Interferon Signature in Secondary Progressive Multiple Sclerosis

Project description:Transcriptome analysis of RNA samples from human PBMCs of IFN-beta-1a (Rebif) therapy in secondary progressive multiple sclerosis (SPMS) patients. Objective: Untreated multiple sclerosis is inflammatory, with decreased immune control and subnormal type I interferon (IFN) signaling. IFN-ß therapy corrects abnormal IFN-ß signaling, reduces inflammation on MRI, exacerbations, and disease worsening in relapsing-remitting MS (RRMS). For unclear reasons, secondary progressive MS (SPMS) exhibits waning attacks, relentless neurodegeneration, and diminished benefits of therapy. Methods: Peripheral blood mononuclear cells and serum were from 10 healthy controls (HC), 9 therapy-naive RRMS, 20 therapy-naïve SPMS, and 10 IFN-ß-treated SPMS patients after therapy washout and four hours after IFN-ß-1a injection. Global gene expression was assayed with sensitive RNA microarrays and multiplexed serum immune and neuroprotective protein assays. Results: Therapy-naive RRMS cells displayed 8,723 differentially expressed genes (DEG), compared to HC, vs. d only 3,936 DEG in therapy-naive SPMS. In SPMS, gene expression was subnormal in the WNT/ß-catenin pathway that suppresses inflammation and enhances blood-brain barrier integrity. Olfactory receptor (OR) genes, linked to lymphocyte migration, were overexpressed in RRMS (111 DEG), intermediate in SPMS (34 DEG) vs. HC, differentiating RRMS from SPMS (p < 0.007). IFN-ß injections in SPMS decreased expression of pro-inflammatory genes and increased anti-inflammatory, anti-oxidant metallothionein genes. Pro-inflammatory and anti-inflammatory protein levels were balanced in HC, disrupted in RRMS, and intermediate in SPMS. Interpretation: Aberrant gene expression seen in RRMS wanes in SPMS, paralleling fewer clinical exacerbations and diminished therapeutic responses. Novel biomarkers for SPMS suggest new targets to correct subnormal immune regulation and brain repair in this neurodegenerative disease.

2024-03-07 | GSE247181 | GEO

Transcriptional response to interferon beta-1a treatment in patients with secondary progressive multiple sclerosis

Project description:Interferon (IFN) beta-1a is an approved treatment for relapsing remitting multiple sclerosis (RRMS) and has been examined for use in secondary progressive multiple sclerosis (SPMS). However, no information regarding blood transcriptional changes induced by IFN treatment in SPMS patients is available. Our aim was to identify a subgroup of SPMS patients presenting a gene expression signature similar to that of RRMS patients who are clinical responders to IFN treatment.

2015-10-06 | GSE73608 | GEO

S1P lyase deficiency disrupts lipid homeostasis in liver

Project description:The cleavage of sphingoid base phosphates by sphingosine-1-phosphate (S1P) lyase to produce phosphoethanolamine and a fatty aldehyde is the final degradative step in the sphingolipid metabolic pathway. We have studied mice with an inactive S1P lyase gene and have found that, in addition to the expected increase of sphingoid base phosphates, other sphingolipids (including sphingosine, ceramide, and sphingomyelin) were substantially elevated in the serum and /or liver of these mice. This latter increase is consistent with a reutilization of the sphingosine backbone for sphingolipid synthesis due to its inability to exit the sphingolipid metabolic pathway. Furthermore, the S1P lyase deficiency resulted in changes in the levels of serum and liver lipids not directly within the sphingolipid pathway, including phospholipids, triacyglycerol, diacylglycerol, and cholesterol. Even though lipids in serum and lipid storage were elevated in liver, adiposity was reduced in the S1P lyase-deficient mice. Microarray analysis of lipid metabolism genes in liver showed that the S1P lyase deficiency caused widespread changes in their expression pattern. These results demonstrate that S1P lyase is a key regulator of the levels of multiple sphingolipid substrates and reveal functional links between the sphingolipid metabolic pathway and other lipid metabolic pathways that may be mediated by shared lipid substrates and changes in gene expression programs. The disturbance of lipid homeostasis by altered sphingolipid levels may be relevant to metabolic diseases. Experiment Overall Design: RNA samples from liver for three sphingosine-1-phosphate lyase knock-out and three WT mice.

2010-02-05 | E-GEOD-18745 | biostudies-arrayexpress

Sphingosine-1-phosphate phosphatase 1 regulates keratinocyte differentiation and epidermal homeostasis

Project description:Sphingosine 1-phosphate (S1P) is a bioactive lipid whose levels are tightly regulated by its synthesis and degradation. Intracellularly, S1P is dephosphoryled by the actions of two S1P-specific phosphatases, sphingosine 1-phosphate phosphatase 1 and 2. To identify the physiologic functions of S1P phosphatase 1, we have studied mice with its gene, Sgpp1, deleted. Sgpp1-/- mice appeared normal at birth but during the first week of life, they exhibited stunted growth, suffered desquamation, and most died before weaning. Interestingly, the epidermal permeability barrier developed normally during embryogenesis. Sgpp1 -/- pups and surviving adults exhibited epidermal hyperplasia and abnormal expression of keratinocyte differentiation markers. Keratinocytes isolated from Sgpp1 -/- skin had increased intracellular S1P levels, and expressed a gene expression profile that indicated enhanced differentiation. The results reveal S1P metabolism as a regulator of keratinocyte differentiation and epidermal homeostasis. Comparison of KO vs. WT with five replications per treatment sample

2013-08-09 | E-GEOD-40368 | biostudies-arrayexpress

Expression profiling of human mesoangioblasts indicates that S1P induces differentiation towards smooth muscle cells

Project description:cDNA microarray study of human mesoangioblasts treated with 1 µM sphingosine 1-phosphate (S1P) at 6 and 24 h. Agilent whole human genome oligonucleotide microarrays (44 K) were used to examine alterations in gene expression of cells after S1P treatment

2011-05-01 | E-GEOD-17596 | biostudies-arrayexpress

Identification of novel binding proteins for sphingosine 1-phosphate

Project description:Novel binding proteins for bioactive lipid mediator sphingosine 1-phosphate (S1P) were searched in the plasma from apolipoprotein M/albumin double deficient mice.

2019-09-04 | PXD015023 | Pride

Transcriptomic profile of multiple sclerosis patients treated with fingolimod

Project description:Fingolimod is an immunomodulatory sphingosine-1-phosphate (S1P) analogue approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). The identification of biomarkers of clinical response to fingolimod is a major necessity in MS to identify optimal responders and avoid the risk of disease progression in non-responders. With this aim, we used RNA-sequencing to study the transcriptomic changes induced by fingolimod in peripheral blood mononuclear cells of MS-treated patients and their association with clinical response. Samples were obtained from 10 RRMS patients (5 responders and 5 non-responders) at baseline and at 12 months of fingolimod therapy. Fingolimod exerted a vast impact at the transcriptional level, identifying 7155 differentially expressed genes (DEGs) compared to baseline that affected the regulation of numerous signalling pathways and cellular processes. These DEGs were predominantly immune-related, including genes associated with S1P metabolism, cytokines, lymphocyte trafficking, master transcription factors of lymphocyte functions and the NF-kB pathway. Responder and non-responder patients exhibited a differential transcriptomic regulation during fingolimod treatment, with responders presenting a higher number of DEGs (6405) compared to non-responders (2653). These transcriptomic differences offer the potential of being exploited as biomarkers of clinical response to fingolimod.

2024-01-31 | GSE250453 | GEO

Sphingosine-1-phosphate phosphatase 1 regulates keratinocyte differentiation and epidermal homeostasis

2013-08-09 | GSE40368 | GEO