Transcriptional profiling of multiple system atrophy cerebellar tissue highlights differences between the parkinsonian and cerebellar sub-types of the disease [cohort 2]
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ABSTRACT:
PROVIDER: PRJNA821228 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18529000.fastq.gz | Fastqsanger.gz | |||
| SRR18529001.fastq.gz | Fastqsanger.gz | |||
| SRR18529002.fastq.gz | Fastqsanger.gz | |||
| SRR18529003.fastq.gz | Fastqsanger.gz | |||
| SRR18529004.fastq.gz | Fastqsanger.gz |
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Project description:Transcriptional profiling of multiple system atrophy cerebellar tissue highlights differences between the parkinsonian and cerebellar sub-types of the disease
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Project description:Transcriptional profiling of multiple system atrophy cerebellar tissue highlights differences between the parkinsonian and cerebellar sub-types of the disease [Oligodendrocytes LCM data]
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Project description:Multiple system atrophy (MSA) is a rare adult-onset neurodegenerative disease of unknown cause, with no effective therapeutic options, and no cure. Limited work to date has attempted to characterize the transcriptional changes associated with the disease, which presents as either predominating parkinsonian (MSA-P) or cerebellar (MSC-C) symptoms. We report here the results of RNA expression profiling of cerebellar white matter (CWM) tissue from two independent cohorts of MSA patients (n = 66) and healthy controls (HC; n = 66). RNA samples from bulk brain tissue and from oligodendrocytes obtained by laser capture microdissection (LCM) were sequenced. Differentially expressed genes (DEGs) were obtained and were examined before and after stratifying by MSA clinical sub-type. We detected the highest number of DEGs in the MSA-C group (n = 747) while only one gene was noted in MSA-P, highlighting the larger dysregulation of the transcriptome in the MSA-C CWM. Results from both bulk tissue and LCM analysis showed a downregulation of oligodendrocyte genes and an enrichment for myelination processes with a key role noted for the QKI gene. Additionally, we observed a significant upregulation of neuron-specific gene expression in MSA-C and enrichment for synaptic processes. A third cluster of genes was associated with the upregulation of astrocyte and endothelial genes, two cell types with a key role in inflammation processes. Finally, network analysis in MSA-C showed enrichment for β-amyloid related functional classes, including the known Alzheimer’s disease (AD) genes, APP and PSEN1. This is the largest RNA profiling study ever conducted on post-mortem brain tissue from MSA patients. We were able to define specific gene expression signatures for MSA-C highlighting the different stages of the complex neurodegenerative cascade of the disease that included alterations in several cell-specific transcriptional programs. Finally, several results suggest a common transcriptional dysregulation between MSA and AD-related genes despite the clinical and neuropathological distinctions between the two diseases.
2022-03-29 | GSE199258 | GEO
Project description:Multiple system atrophy (MSA) is a rare adult-onset neurodegenerative disease of unknown cause, with no effective therapeutic options, and no cure. Limited work to date has attempted to characterize the transcriptional changes associated with the disease, which presents as either predominating parkinsonian (MSA-P) or cerebellar (MSC-C) symptoms. We report here the results of RNA expression profiling of cerebellar white matter (CWM) tissue from two independent cohorts of MSA patients (n = 66) and healthy controls (HC; n = 66). RNA samples from bulk brain tissue and from oligodendrocytes obtained by laser capture microdissection (LCM) were sequenced. Differentially expressed genes (DEGs) were obtained and were examined before and after stratifying by MSA clinical sub-type. We detected the highest number of DEGs in the MSA-C group (n = 747) while only one gene was noted in MSA-P, highlighting the larger dysregulation of the transcriptome in the MSA-C CWM. Results from both bulk tissue and LCM analysis showed a downregulation of oligodendrocyte genes and an enrichment for myelination processes with a key role noted for the QKI gene. Additionally, we observed a significant upregulation of neuron-specific gene expression in MSA-C and enrichment for synaptic processes. A third cluster of genes was associated with the upregulation of astrocyte and endothelial genes, two cell types with a key role in inflammation processes. Finally, network analysis in MSA-C showed enrichment for β-amyloid related functional classes, including the known Alzheimer’s disease (AD) genes, APP and PSEN1. This is the largest RNA profiling study ever conducted on post-mortem brain tissue from MSA patients. We were able to define specific gene expression signatures for MSA-C highlighting the different stages of the complex neurodegenerative cascade of the disease that included alterations in several cell-specific transcriptional programs. Finally, several results suggest a common transcriptional dysregulation between MSA and AD-related genes despite the clinical and neuropathological distinctions between the two diseases.
2022-04-03 | GSE199715 | GEO
Project description:Multiple system atrophy (MSA) is a rare adult-onset neurodegenerative disease of unknown cause, with no effective therapeutic options, and no cure. Limited work to date has attempted to characterize the transcriptional changes associated with the disease, which presents as either predominating parkinsonian (MSA-P) or cerebellar (MSC-C) symptoms. We report here the results of RNA expression profiling of cerebellar white matter (CWM) tissue from two independent cohorts of MSA patients (n = 66) and healthy controls (HC; n = 66). RNA samples from bulk brain tissue and from oligodendrocytes obtained by laser capture microdissection (LCM) were sequenced. Differentially expressed genes (DEGs) were obtained and were examined before and after stratifying by MSA clinical sub-type. We detected the highest number of DEGs in the MSA-C group (n = 747) while only one gene was noted in MSA-P, highlighting the larger dysregulation of the transcriptome in the MSA-C CWM. Results from both bulk tissue and LCM analysis showed a downregulation of oligodendrocyte genes and an enrichment for myelination processes with a key role noted for the QKI gene. Additionally, we observed a significant upregulation of neuron-specific gene expression in MSA-C and enrichment for synaptic processes. A third cluster of genes was associated with the upregulation of astrocyte and endothelial genes, two cell types with a key role in inflammation processes. Finally, network analysis in MSA-C showed enrichment for β-amyloid related functional classes, including the known Alzheimer’s disease (AD) genes, APP and PSEN1. This is the largest RNA profiling study ever conducted on post-mortem brain tissue from MSA patients. We were able to define specific gene expression signatures for MSA-C highlighting the different stages of the complex neurodegenerative cascade of the disease that included alterations in several cell-specific transcriptional programs. Finally, several results suggest a common transcriptional dysregulation between MSA and AD-related genes despite the clinical and neuropathological distinctions between the two diseases.
2022-04-03 | GSE199724 | GEO
Project description:Multiple system atrophy (MSA) is a rare adult-onset neurodegenerative disease of unknown cause, with no effective therapeutic options, and no cure. Limited work to date has attempted to characterize the transcriptional changes associated with the disease, which presents as either predominating parkinsonian (MSA-P) or cerebellar (MSC-C) symptoms. We report here the results of RNA expression profiling of cerebellar white matter (CWM) tissue from two independent cohorts of MSA patients (n?=?66) and healthy controls (HC; n?=?66). RNA samples from bulk brain tissue and from oligodendrocytes obtained by laser capture microdissection (LCM) were sequenced. Differentially expressed genes (DEGs) were obtained and were examined before and after stratifying by MSA clinical sub-type.We detected the highest number of DEGs in the MSA-C group (n?=?747) while only one gene was noted in MSA-P, highlighting the larger dysregulation of the transcriptome in the MSA-C CWM. Results from both bulk tissue and LCM analysis showed a downregulation of oligodendrocyte genes and an enrichment for myelination processes with a key role noted for the QKI gene. Additionally, we observed a significant upregulation of neuron-specific gene expression in MSA-C and enrichment for synaptic processes. A third cluster of genes was associated with the upregulation of astrocyte and endothelial genes, two cell types with a key role in inflammation processes. Finally, network analysis in MSA-C showed enrichment for ?-amyloid related functional classes, including the known Alzheimer's disease (AD) genes, APP and PSEN1.This is the largest RNA profiling study ever conducted on post-mortem brain tissue from MSA patients. We were able to define specific gene expression signatures for MSA-C highlighting the different stages of the complex neurodegenerative cascade of the disease that included alterations in several cell-specific transcriptional programs. Finally, several results suggest a common transcriptional dysregulation between MSA and AD-related genes despite the clinical and neuropathological distinctions between the two diseases.
| S-EPMC7268362 | biostudies-literature
Project description:TRIP4 is one of the subunits of the transcriptional coregulator ASC-1, a ribonucleoprotein complex that participates in transcriptional coactivation and RNA processing events. Recessive variants in the TRIP4 gene have been associated with spinal muscular atrophy with bone fractures as well as a severe form of congenital muscular dystrophy. Here we present the diagnostic journey of a patient with cerebellar hypoplasia and spinal muscular atrophy (PCH1) and congenital bone fractures. Initial exome sequencing analysis revealed no candidate variants. Reanalysis of the exome data by inclusion in the Solve-RD project resulted in the identification of a homozygous stop-gain variant in the TRIP4 gene, previously reported as disease-causing. This highlights the importance of analysis reiteration and improved and updated bioinformatic pipelines. Proteomic profile of the patient’s fibroblasts showed altered RNA-processing and impaired exosome activity supporting the pathogenicity of the detected variant. In addition, we identified a novel genetic form of PCH1, further strengthening the link of this characteristic phenotype with altered RNA metabolism.
2022-02-16 | PXD023584 | Pride
Project description:Background: Microarray technology may offer a new opportunity to gain insight into disease-specific global protein expression profiles. The present study was performed to apply a serum cytokine-array to screen for potential molecular biomarkers for Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Methodology/Principal Findings: Serum samples were obtained from patients with clinical diagnoses of PD (n=117), MSA (n=31) and PSP/CBS (n=38) and 99 controls. Cytokine profiles of sera of patients and controls were analyzed with a semiquantitative human cytokine antibody array. In a next step, significantly altered cytokines were individually validated by immunoassays. The cytokine array revealed a significantly altered expression of 12 cytokines. Immunoassay validation confirmed a significant increase of PDGF-BB in PSP/CBS, MSA and PD and a decrease of Prolactin in PD (Kruskal-Wallis p<0.05). A multivariate analysis taking into account diagnoses anti-Parkinsonian treatment, sex and age revealed that PDGF-BB levels were influenced only by the diagnoses (p<0.001), whereas Prolactin levels were influenced only by anti-Parkinsonian treatment (p<0.001). These findings could be corroborated by a subgroup analysis in untreated patients. Conclusions/Significance: In our unbiased cytokine array screening approach we found PDGF-BB to be elevated in PSP/CBS, MSA and PD. Increased PDGF-BB levels might be of relevance in a model of molecular biomarkers for Parkinsonian syndromes. Screen serum samples from patients with Parkinson's disease, progressive supranuclear palsy, corticobasal syndrome, multisystem atrophy and controls for deregulation of serum proteins using a cytokine-array detecting 174 secreted signaling proteins.
2011-11-23 | E-GEOD-32037 | biostudies-arrayexpress
Project description:Background: Microarray technology may offer a new opportunity to gain insight into disease-specific global protein expression profiles. The present study was performed to apply a serum cytokine-array to screen for potential molecular biomarkers for Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Methodology/Principal Findings: Serum samples were obtained from patients with clinical diagnoses of PD (n=117), MSA (n=31) and PSP/CBS (n=38) and 99 controls. Cytokine profiles of sera of patients and controls were analyzed with a semiquantitative human cytokine antibody array. In a next step, significantly altered cytokines were individually validated by immunoassays. The cytokine array revealed a significantly altered expression of 12 cytokines. Immunoassay validation confirmed a significant increase of PDGF-BB in PSP/CBS, MSA and PD and a decrease of Prolactin in PD (Kruskal-Wallis p<0.05). A multivariate analysis taking into account diagnoses anti-Parkinsonian treatment, sex and age revealed that PDGF-BB levels were influenced only by the diagnoses (p<0.001), whereas Prolactin levels were influenced only by anti-Parkinsonian treatment (p<0.001). These findings could be corroborated by a subgroup analysis in untreated patients. Conclusions/Significance: In our unbiased cytokine array screening approach we found PDGF-BB to be elevated in PSP/CBS, MSA and PD. Increased PDGF-BB levels might be of relevance in a model of molecular biomarkers for Parkinsonian syndromes. Screen serum samples from patients with Parkinson's disease, progressive supranuclear palsy, corticobasal syndrome, multisystem atrophy and controls for deregulation of serum proteins using a cytokine-array detecting 174 secreted signaling proteins.
2011-11-23 | E-GEOD-32040 | biostudies-arrayexpress
Project description:Background: Microarray technology may offer a new opportunity to gain insight into disease-specific global protein expression profiles. The present study was performed to apply a serum cytokine-array to screen for potential molecular biomarkers for Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Methodology/Principal Findings: Serum samples were obtained from patients with clinical diagnoses of PD (n=117), MSA (n=31) and PSP/CBS (n=38) and 99 controls. Cytokine profiles of sera of patients and controls were analyzed with a semiquantitative human cytokine antibody array. In a next step, significantly altered cytokines were individually validated by immunoassays. The cytokine array revealed a significantly altered expression of 12 cytokines. Immunoassay validation confirmed a significant increase of PDGF-BB in PSP/CBS, MSA and PD and a decrease of Prolactin in PD (Kruskal-Wallis p<0.05). A multivariate analysis taking into account diagnoses anti-Parkinsonian treatment, sex and age revealed that PDGF-BB levels were influenced only by the diagnoses (p<0.001), whereas Prolactin levels were influenced only by anti-Parkinsonian treatment (p<0.001). These findings could be corroborated by a subgroup analysis in untreated patients. Conclusions/Significance: In our unbiased cytokine array screening approach we found PDGF-BB to be elevated in PSP/CBS, MSA and PD. Increased PDGF-BB levels might be of relevance in a model of molecular biomarkers for Parkinsonian syndromes. Screen serum samples from patients with Parkinson's disease, progressive supranuclear palsy, corticobasal syndrome, multisystem atrophy and controls for deregulation of serum proteins using a cytokine-array detecting 174 secreted signaling proteins.
2011-11-23 | E-GEOD-32039 | biostudies-arrayexpress