Altered Nucleocytoplasmic Proteome and Transcriptome Distributions in an In Vitro Model of Amyotrophic Lateral Sclerosis
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE90913 | GEO | 2017/03/01
SECONDARY ACCESSION(S): PRJNA356400
REPOSITORIES: GEO
Similar Datasets
Project description:Identification of amyotrophic lateral sclerosis (ALS) associated genes. Post mortem spinal cord grey matter from sporadic and familial ALS patients compared with controls. Keywords: other
2003-11-14 | GSE833 | GEO
Project description:Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive motor neuron (MN) degeneration in the brain and spinal cord. Although neuroinflammation is increasingly recognized as a hallmark of ALS, the precise molecular programs linking immune responses to MN pathology remain poorly defined. Using an integrated approach that combines single-cell and bulk RNA sequencing with spatial proteogenomics, we characterized both shared and distinct immune dynamics in peripheral blood and spinal cord tissues from sporadic ALS patients and patients carrying C9orf72 repeat expansions. Our analysis revealed broad immune remodeling in C9orf72-ALS, ALS subtype-specific and progression-associated differences in monocyte activation, and antigen-experienced CD8 effector memory T cells with clonal features consistent with antigen-driven responses. Spatial mapping revealed complement activation and lipid-programmed myeloid states converging at sites of MN loss and TDP-43 pathology. Together, these findings connect peripheral and central immune alterations to ALS heterogeneity and highlight stratified immunomodulation as a potential therapeutic strategy.
2026-04-28 | GSE288365 | GEO
Project description:Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive motor neuron (MN) degeneration in the brain and spinal cord. Although neuroinflammation is increasingly recognized as a hallmark of ALS, the precise molecular programs linking immune responses to MN pathology remain poorly defined. Using an integrated approach that combines single-cell and bulk RNA sequencing with spatial proteogenomics, we characterized both shared and distinct immune dynamics in peripheral blood and spinal cord tissues from sporadic ALS patients and patients carrying C9orf72 repeat expansions. Our analysis revealed broad immune remodeling in C9orf72-ALS, ALS subtype-specific and progression-associated differences in monocyte activation, and antigen-experienced CD8 effector memory T cells with clonal features consistent with antigen-driven responses. Spatial mapping revealed complement activation and lipid-programmed myeloid states converging at sites of MN loss and TDP-43 pathology. Together, these findings connect peripheral and central immune alterations to ALS heterogeneity and highlight stratified immunomodulation as a potential therapeutic strategy.
2026-04-28 | GSE268995 | GEO
Project description:Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share key features, including accumulation of the RNA binding protein TDP-43. TDP-43 regulatesRNA homeostasis, but it remains unclear whether RNA stability is affected in these disorders. We used Bru-seq and BruChase-seq to assessgenome-wide RNA stabilityinALS patient-derived cells,demonstratingprofound destabilization of ribosomal and mitochondrial transcripts. This pattern wasrecapitulatedbyTDP-43 overexpression, suggesting a primary role for TDP-43 in RNA destabilization, and in post-mortem samples from ALS and FTD patients. Proteomics and functional studies illustrated corresponding reductionsin mitochondrial components and compensatory increasesin protein synthesis. Collectively, these observations suggest that TDP-43 deposition leads to targeted RNA instability in ALS and FTD, ultimately causing cell death by disrupting energy production and protein synthesis pathways.
2018-07-25 | GSE115310 | GEO
Project description:Circular RNAs are abundant, covalently closed transcripts that arise in cells through back-splicing and display distinct expression patterns across cells and developmental stages. While their functions are largely unknown, their intrinsic stability has made them valuable biomarkers in diseases like cancer. Here, we set out to examine circRNA patterns in amyotrophic lateral sclerosis (ALS). By RNA-sequencing analysis, we first identified circRNAs and linear RNAs that were differentially abundant in skeletal muscle biopsies from ALS and normal individuals. Among these, 8 circRNAs were significantly elevated and 10 significantly reduced in ALS, while the linear counterparts, arising from shared precursor RNAs, did not change. Several of these circRNAs were also differentially abundant in motor neurons derived from human induced pluripotent stem cells (iPSCs) bearing ALS mutations, and across different disease stages in skeletal muscle from a mouse model of ALS (SOD1G93A). Interestingly, several of the circRNAs significantly elevated in muscle were significantly reduced in the spinal cord from ALS patients and ALS (SOD1G93A) mice. In sum, we have identified differentially abundant circRNAs in ALS-relevant tissues (muscle and spinal cord) that could inform about neuromuscular molecular programs in ALS and guide the development of therapies.
2023-02-01 | GSE215364 | GEO
Project description:Circular RNAs are abundant, covalently closed transcripts that arise in cells through back-splicing and display distinct expression patterns across cells and developmental stages. While their functions are largely unknown, their intrinsic stability has made them valuable biomarkers in diseases like cancer. Here, we set out to examine circRNA patterns in amyotrophic lateral sclerosis (ALS). By RNA-sequencing analysis, we first identified circRNAs and linear RNAs that were differentially abundant in skeletal muscle biopsies from ALS and normal individuals. Among these, 8 circRNAs were significantly elevated and 10 significantly reduced in ALS, while the linear counterparts, arising from shared precursor RNAs, did not change. Several of these circRNAs were also differentially abundant in motor neurons derived from human induced pluripotent stem cells (iPSCs) bearing ALS mutations, and across different disease stages in skeletal muscle from a mouse model of ALS (SOD1G93A). Interestingly, several of the circRNAs significantly elevated in muscle were significantly reduced in the spinal cord from ALS patients and ALS (SOD1G93A) mice. In sum, we have identified differentially abundant circRNAs in ALS-relevant tissues (muscle and spinal cord) that could inform about neuromuscular molecular programs in ALS and guide the development of therapies.
2023-02-01 | GSE215363 | GEO
Project description:Identification of familial amyotrophic lateral sclerosis (fALS) related genes. Material from three hSOD1(G93A) transgenic mice was compared to material from three non-transgenic control mice using an alternating loop design on two-colour cDNA microarrays. Statistical data management and analysis: postgreSQL relational database (www.postgresql.org), Perl, and R (www.r-project.org); pin-wise lowess-regression based normalisation (Yang et al., 2002 [PMID: 11842121]); mixed ANOVA-model. Keywords = amyotrophic lateral sclerosis, ALS, SOD1 mouse model
2010-06-05 | E-GEOD-2400 | biostudies-arrayexpress
Project description:<p>Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with unclear etiology and no effective cure. Accumulating evidence implicates gut microbiota dysbiosis and circulatory metabolic al-terations in ALS pathogenesis, potentially driving disease progression and severity.</p><p>Methods: We enrolled 36 ALS patients and 32 healthy household relatives of these ALS patients as controls to minimize environmental confounders. Fecal (n=61) and serum (n=68) samples were analyzed using metagenomic sequencing for gut microbiota composition and untargeted metabolomics for fecal and serum metabolic profiles. Statistical and machine learning approaches, including principal coordinate analysis (PCoA), linear discriminant analysis effect size (LEfSe), and random forest modeling, identified differentially abundant taxa, metabolites, and biomarkers.</p><p>Results: ALS gut microbiota showed distinct beta diversity but unchanged alpha diversity. Pathogenic Proteobacteria (Enterobacteriaceae, Desulfovibrioaceae) increased, while beneficial Faecalibacterium and Clostridium decreased. A random forest model identified 20 microbial genera (AUC=0.89) and species (AUC=0.92) as ALS biomarkers. Microbial functions indicated hyperactive carbohydrate and amino acid metabolism and suppressed fatty acid metabolism. Fecal metabolomics revealed 722 altered metabolites (670 downregulated, e.g., lipids; 52 upregulated), disrupting phenylpropanoid biosynthesis and linoleic acid metabolism. Serum metabolomics showed lipid and choline metabolism perturbations. Reduced creatine and 2-hydroxybutyrate correlated with lower ALS Functional Rating Scale-Revised scores, while elevated diacylglycerols tracked disease severity. Symbiotic network analysis linked pathogenic Erysipelatoclostridium to reduced beneficial metabolites. Eubacterium was a central node, influencing metabolomes and BMI, with higher BMI correlating with Firmicutes enrichment (e.g., Ruminococcus).</p><p>Conclusion: ALS patients exhibit gut microbiota dysbiosis and circulatory metabolic disruptions, shaped by host factors like BMI and disease severity, correlating with disease progression. The microbiota-metabolite axis, elucidated through multi-omics and network analyses, offers targets for non-invasive biomarkers and therapies like microbiota modulation.</p>
2026-04-07 | MTBLS13295 | MetaboLights
Project description:Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share key features, including accumulation of the RNA binding protein TDP-43. TDP-43 regulates RNA homeostasis, but it remains unclear whether RNA stability is affected in these disorders. We use Bru-seq and BruChase-seq to assess genome-wide RNA stability in ALS patient-derived cells, demonstrating profound destabilization of ribosomal and mitochondrial transcripts. This pattern is recapitulated by TDP-43 overexpression, suggesting a primary role for TDP-43 in RNA destabilization, and in post-mortem samples from ALS and FTD patients. Proteomics and functional studies illustrate corresponding reductions in mitochondrial components and compensatory increases in protein synthesis. Collectively, these observations suggest that TDP-43 deposition leads to targeted RNA instability in ALS and FTD, and may ultimately cause cell death by disrupting energy production and protein synthesis pathways.
2018-07-24 | PXD009969 | Pride
Project description:Despite smell impairment has been considered a potential non-motor finding in ALS, the pathobiochemistry at olfactory level remains unknown. Here, we applied an olfactory quantitative proteotyping approach to analyze the magnitude of the olfactory bulb (OB) proteostatic imbalance in ALS subjects (n=12) respect to controls (n=8).
2021-09-09 | PXD021630 | Pride