Integrative genome-wide analysis of PBMCs confirmed SOD1-specific functionality of ATF3 in ALS blood
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA928484 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23249032.fastq.gz | Fastqsanger.gz | |||
| SRR23249033.fastq.gz | Fastqsanger.gz | |||
| SRR23249034.fastq.gz | Fastqsanger.gz | |||
| SRR23249035.fastq.gz | Fastqsanger.gz | |||
| SRR23249036.fastq.gz | Fastqsanger.gz |
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Project description:Amyotrophic Lateral Sclerosis (ALS) is characterized by a progressive loss of upper and lower motor neurons, leading to progressive weakness and atrophy of limb, bulbar and respiratory muscles. Since genetics alone fails to explain the etiology of ALS, the investigation of the epigenome might provide novel insights in disease mechanisms. Among all the different histone modifications the repressive trimethylation of lysine 27 on histone H3 (H3K27me3) is of particular interest in the context of ALS for several reasons. In this study, we interrogate the epigenetic landscape in peripheral blood mononuclear cells (PBMCs) of fALS patient with either chromosome 9 open reading frame 72 (C9orf72) or superoxide dismutase 1 (SOD1) mutation and aimed to identify key epigenetic footprints of the disease. To this end, we used an integrative approach that combines chromatin immunoprecipitation targeting H3K27me3 (ChIP-Seq) with the matching gene expression data to gain new insights into the impact of chromatin remodeling on ALS-related molecular mechanisms. In particular, multiple lines of evidence in this work indicated that one of the hub molecules that modulates changes in PBMC transcriptome in SOD1-positive ALS cases is ATF3. We also reported a potential suppression of SNAP25, with ATF3 involved as well, in SOD1-positive ALS blood.
2023-07-01 | GSE223834 | GEO
Project description:Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease caused by loss of motor neurons. SOD1 may have a toxic role in the pathogenesis of ALS when the protein aggregates in the cytoplasm; increased accumulation of soluble nuclear SOD1 (nSOD1) represents a protective cellular reaction.
2022-01-26 | GSE183204 | GEO
Project description:Recent genetic studies of ALS patients have identified several forms of ALS that are associated with mutations in RNA binding proteins. In animals or cultured cells, such defects broadly affect RNA metabolism. This raises the question of whether all forms of ALS have general effects on RNA metabolism. We tested this hypothesis in a mouse model of ALS that is transgenic for a human disease-causing mutation in the enzyme superoxide dismutase 1 (SOD1). We analyzed RNA from laser-captured spinal cord motor neuron cell bodies of the mutant SOD1 strain, comparing the RNA profile with that from a corresponding wild-type SOD1 transgenic strain. We prepared the samples from animals that were presymptomatic, but which manifested abnormalities at the cellular level that are seen in ALS, including aggregation of the mutant protein in motor neuron cell bodies and defective morphology of neuromuscular junctions, the connections between neuron and muscle. We observed only minor changes in the level and splicing of RNA in the SOD1 mutant animals as compared with wild-type, suggesting that mutant SOD1 produces the toxic effects of ALS by a mechanism that does not involve global RNA disturbance. RNA-Seq of laser microdissection of motor neuron bodies from two biological replicates each of SOD1 YFP (wildtype 592) and SOD1 G85R YFP (737) transgenic mice.
2012-12-04 | E-GEOD-38820 | biostudies-arrayexpress
Project description:Recent genetic studies of ALS patients have identified several forms of ALS that are associated with mutations in RNA binding proteins. In animals or cultured cells, such defects broadly affect RNA metabolism. This raises the question of whether all forms of ALS have general effects on RNA metabolism. We tested this hypothesis in a mouse model of ALS that is transgenic for a human disease-causing mutation in the enzyme superoxide dismutase 1 (SOD1). We analyzed RNA from laser-captured spinal cord motor neuron cell bodies of the mutant SOD1 strain, comparing the RNA profile with that from a corresponding wild-type SOD1 transgenic strain. We prepared the samples from animals that were presymptomatic, but which manifested abnormalities at the cellular level that are seen in ALS, including aggregation of the mutant protein in motor neuron cell bodies and defective morphology of neuromuscular junctions, the connections between neuron and muscle. We observed only minor changes in the level and splicing of RNA in the SOD1 mutant animals as compared with wild-type, suggesting that mutant SOD1 produces the toxic effects of ALS by a mechanism that does not involve global RNA disturbance.
2012-12-04 | GSE38820 | GEO
Project description:Whole-genome profiling of SH-SY5Y cells was done on neuroblastoma SH-SY5Y stably transfected with cDNAs coding for SOD1WT or the mutant SOD1(G93A) protein.
2010-12-22 | GSE21298 | GEO
Project description:Whole-genome profiling of SH-SY5Y cells was done on neuroblastoma SH-SY5Y stably transfected with cDNAs coding for SOD1WT or the mutant SOD1(G93A) protein. Five wt SOD versus five mutant SOD
2010-12-22 | E-GEOD-21298 | biostudies-arrayexpress
Project description:Amyotrophic Lateral Sclerosis (ALS) is generally a late onset neurodegenerative disease. Mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene accounts for approximately 20% of familial ALS and 2% of all ALS cases. Although a number of hypothesis have been proposed to explain mutant SOD1 toxicity, the molecular mechanisms of the disease remain unclear. SOD1 linked ALS is thought to function in a non-cell autonomous manner such that the motoneurons are critical for the onset and glia contribute to the progress of the disease. To dissect the roles of motoneurons and glia, we used the Gal4-UAS system to determine gene expression changes following the expression of mutant human SOD1 (G85R) selectively in either motoneurons or glia, and concurrently in motoneurons and glia of flies. We conducted a microarray on young (5 days old) and old (45 days old) flies expressing G85R in these cell types and identified a number of genes involved in a variety of processes. The candidate genes identified by this screen may help elucidate the individual and combined contributions of motoneurons and glial cells in ALS. We used microarrays to evaluate the transcriptional profile of 5 day old and 45 day old flies expressing mutant human SOD1 (G85R) in a tissue specific manner in motoneurons, glia, and together in motoneurons and glia and compared the expression to flies expressing wild-type drosophila SOD1 controls. The Gal4-UAS system was used to drive tissue expression of either mutant human SOD1 (G85R) or wild-type drosophila SOD1 (dSOD1) in flies. Flies containing either the motoneuronal driver, D42-Gal4, the glial driver, M1B-Gal4, or the combined motoneuronal and glial drivers, D42+M1B-Gal4 were crossed to flies containing either mutant human SOD1, UAS-G85R, or wild-type drosophila SOD1, UAS-dSOD1, as a control. Adult male progeny were collected within 24 hours after eclosion and aged to 5 (5d) and 45 (45d) days old. Groups of 10 flies were maintained in vials of cornmeal agar food and transferred to fresh food every 5-7 days. For each Gal4-UAS line and each age, 3 biological replicates consisting of 40 whole flies were flash frozen in liquid nitrogen and used to isolate total RNA, for a total of 36 samples.
2012-06-30 | E-GEOD-37148 | biostudies-arrayexpress
Project description:Amyotrophic Lateral Sclerosis (ALS) is generally a late onset neurodegenerative disease. Mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene accounts for approximately 20% of familial ALS and 2% of all ALS cases. Although a number of hypothesis have been proposed to explain mutant SOD1 toxicity, the molecular mechanisms of the disease remain unclear. SOD1 linked ALS is thought to function in a non-cell autonomous manner such that the motoneurons are critical for the onset and glia contribute to the progress of the disease. To dissect the roles of motoneurons and glia, we used the Gal4-UAS system to determine gene expression changes following the expression of mutant human SOD1 (G85R) selectively in either motoneurons or glia, and concurrently in motoneurons and glia of flies. We conducted a microarray on young (5 days old) and old (45 days old) flies expressing G85R in these cell types and identified a number of genes involved in a variety of processes. The candidate genes identified by this screen may help elucidate the individual and combined contributions of motoneurons and glial cells in ALS. We used microarrays to evaluate the transcriptional profile of 5 day old and 45 day old flies expressing mutant human SOD1 (G85R) in a tissue specific manner in motoneurons, glia, and together in motoneurons and glia and compared the expression to flies expressing wild-type drosophila SOD1 controls.
2012-07-01 | GSE37148 | GEO
Project description:Amyotrophic lateral sclerosis (ALS) is caused by the progressive degeneration of motor neurons. Mutations in the Cu/Zn superoxide dismutase (SOD1) are found in about 20% of patients with familial ALS. Mutant SOD1 causes motor neuron death through an acquired toxic property. Although, molecular mechanism underlying this toxic gain-of-function remains unknown, evidence support the role of mutant SOD1 expression in non-neuronal cells in shaping motor neuron degeneration. We have previously found that in contrast to non-transgenic, SOD1G93A-expressing astrocytes induced apoptosis of co-cultured motor neurons. This prompted us to investigate whether the effect on motor neuron survival was related to a change in the gene expression profile. Through high-density oligonucletide microarrays we found changes in the expression of genes involved in transcription, signaling, cell proliferation, extracellular matrix construction, response to stress and steroid and lipid metabolism. Decorin, a small multifunctional proteoglycan, was the most up-regulated gene. Down-regulated genes included the insulin-like growth factor-1 receptor and the RNA binding protein ROD1. We also analyzed the expression of selected genes in purified motor neurons expressing SOD1G93A and in spinal cord of asymptomatic and early symptomatic ALS-rodent model. The expression of mutated SOD1 in astrocytes cause gene expression changes with potential consequences for its interaction with motor neurons. The astrocyte-specific gene expression profile contributes to the identification of possible candidates for cell type-specific therapies in ALS Keywords: Cell type comparison
2008-12-18 | GSE7441 | GEO
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2020-09-11 | PXD021396 | Pride