Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNAseq functional analysis of SMA model in C. elegans at the L4 stage

ABSTRACT: This dataset comprises RNA sequencing and downstream functional analyses of Caenorhabditis elegans models of spinal muscular atrophy (SMA). Samples were collected at the early L4 larval stage from wildtype and smn-1 mutant strains to assess gene expression changes associated with SMA phenotype onset. The submitted data include processed tables for gene ontology enrichment, alternative splicing events, and differential gene expression analyses performed to characterize molecular pathways impacted by smn-1 deficiency. Raw reads for all samples are available in ENA under the provided accession numbers. This dataset supports the findings published in the corresponding manuscript describing SMA pathomechanisms using C. elegans as a model organism.

INSTRUMENT(S): Illumina NovaSeq 6000, Microcentrifuge, vortex spinner, pipettes, -80C freezer, Zeiss Stereomicroscope, standard lab plasticware, Thermal cycler, Agilent BioAnalyzer 2100

ORGANISM(S): Caenorhabditis elegans

SUBMITTER: Saman Rashid

PROVIDER: E-MTAB-16084 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Developmental arrest of Drosophila survival motor neuron (Smn) mutants accounts for differences in expression of minor intron-containing genes

Project description:RNA-seq was used to analyze mRNA levels and splicing differences between wild-type (Oregon R) and Smn null mutant larvae. Illumina RNA-seq of Oregon R and Smn mutant age-matched larvae from RNA extracted on day four post egg laying. Conclusions from this study used the publicly available modENCODE data from Graveley et al. Nature 2011 (in addition to our RNA-seq data). We downloaded their SRA files, dumped them to fastq files, and put them through our same analysis pipelines. The renalysis data and details are provided in 'reanalysis.tar' and readme_reanalysis.txt. The Cufflinks processed file outputs (22 files in 'Cufflinks_outputs.tar') are derived from all of our raw sample files and all of the developmental data mentioned in the readme.txt file. The file format and content description is provided in the 'readme_for_Cufflinks.txt' Unlike Cufflinks cuffdiff analysis that merged our data with the developmental data, the MISO and DEXSeq analysis was carried out in parallel with analysis of our samples. This generated two additional files for the DEXSeq developmental analysis (DEXSeq output; paired end developmental Graveley et al. Nature 2011): L2_L3P1_2_DEUtable.txt L312hr_L3P1_2_DEUtable.txt Please note that MISO lacks the capacity to incorporate replicates, which contributed to the abundance of these file types. MISO output file names are prepended with the respective sample/raw data names. For example, EG003_EG007.*miso_bf.txt.gz are MISO comparison of Ore-R R1 (EG003) and Smn R1 (EG007).

2013-08-07 | E-GEOD-49587 | biostudies-arrayexpress

SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy

Project description:Characterization of the selectivity of SMN splicing modifiers in SMA type I fibroblasts by RNASeq In total 12 samples were analyzed, divided into four distinct groups (treated with SMN-C3 @ 500 nM; controls for SMN-C3; treated with SMN-C1 @ 100 nM; controls for SMN-C1) containing 3 replicates each.

2014-10-22 | E-GEOD-62540 | biostudies-arrayexpress

KIF5A downregulation in spinal muscular atrophy links axonal regeneration defects with ALS

Project description:Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder caused by mutations in the Survival Motor Neuron 1 (SMN1) gene, leading to decreased SMN levels and motor neuron dysfunction. SMN-restoring therapies offer clinical benefit, but the downstream molecular consequences of SMN reduction remain incompletely understood. Here, we demonstrate that SMN deficiency results in downregulation of KIF5A in human neurons and in a mouse model of SMA. We provide evidence that reduced SMN levels impair axon regeneration, which is rescued by KIF5A overexpression and that the RNA-binding protein SMN functions to stabilize KIF5A mRNA. These findings provide evidence of a molecular link between SMA and ALS pathophysiology, highlighting KIF5A as a new SMN target. Our findings suggest SMN-independent interventions targeting KIF5A could represent a complementary therapeutic approach for SMA and other motor neuron diseases.

2026-03-11 | GSE302774 | GEO

Gain of toxic function by long-term SMN overexpression in the sensory-motor circuit.

Project description:The neurodegenerative disease spinal muscular atrophy (SMA) is a leading genetic cause of infant death caused by deficiency in the survival motor neuron (SMN) protein. Currently approved SMA treatments aim to restore SMN, but the potential for expression of SMN beyond physiological levels is a unique feature of AAV9-SMN gene therapy. Here, we show that long-term AAV9-mediated SMN overexpression in mouse models induces dose-dependent, late-onset motor dysfunction associated with loss of proprioceptive synapses and neurodegeneration. Mechanistically, aggregation of overexpressed SMN in the cytoplasm of motor circuit neurons sequesters components of small nuclear ribonucleoproteins (snRNPs), leading to splicing dysregulation and widespread transcriptome abnormalities with prominent signatures of neuroinflammation and innate immune response. Thus, long-term SMN overexpression can interfere with its normal activity in RNA regulation and trigger SMA-like pathogenic events through toxic gain of function mechanisms. These unanticipated, SMN-dependent and neuron-specific liabilities of AAV9-SMN warrant further evaluation of the long-term safety of gene therapy in SMA.

2021-02-01 | GSE149391 | GEO

Multi-omic analysis identifies APC/C-mediated degradation of SMN in neurons

Project description:Spinal muscular atrophy (SMA) due to loss-of-function of SMN protein is associated with severe loss of voluntary muscle control and is a leading inherited cause of infant mortality. SMA treatments will benefit from in-depth knowledge of functional pathways disrupted in disease and identification of SMN modulators. Here, we present a comprehensive temporal profile of proteogenomic expression patterns in developing mouse spinal cords (Δ7 model), alongside endpoint analyses of human spinal and ventral root tissues in SMA disease, identifying targets for assessing disease progression and treatment response. SMA disease results in development-associated deficiencies in transcription, translation initiation, intracellular transport, and protein folding, and diminished RNA translation efficiency for proteins important in axon development/myelination. The broad impact of SMN deficiency prompted the search for co-regulated proteins that modulate SMN protein levels, resulting in identification of the anaphase promoting complex/cyclosome (APC/C) E3 ubiquitin ligase as a potential modulator of SMN protein stability. Functional studies of APC/C showed that both SMN and HuD are specific interactors of the APC/C in neurons and that selective APC/C inhibition significantly limited SMN and HuD degradation. Finally, we demonstrate that APC/C inhibition rescues motor axon defects characteristic of SMA in a zebrafish model of SMA disease.

2022-01-18 | GSE128129 | GEO

Prenatal SMN-dependent defects in translation uncover a reversible primary ciliopathy in spinal muscular atrophy

Project description:Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein resulting from mutations in the SMN1 gene. Several therapeutic approaches capable of boosting SMN are now approved for use in human patients, delivering remarkable improvements in lifespan and symptom severity. However, new and unexpected phenotypes are being reported in treated SMA patients, including growing evidence for significant neurodevelopmental comorbidities in some individuals, indicative of alterations in brain development. Here, using a mouse model of severe SMA, we reveal an underlying neurodevelopmental phenotype in SMA where prenatal SMN-dependent defects in translation drive a primary ciliopathy in the CNS. Cell proliferation was significantly reduced in the hippocampus of SMA mice at E14.5, accompanied by widespread perturbations in translation, disrupting genes associated with primary cilia. The density of primary cilia in vivo, as well as cilial length in vitro, was significantly decreased in prenatal SMA mice, revealing core morphological hallmarks of a primary ciliopathy. Prenatal transplacental therapeutic intervention with an SMN-restoring small molecule (Risdiplam) rescued primary cilia defects in SMA mouse embryos. We conclude that SMN protein is required for normal cellular and molecular development of the CNS, with low levels in SMA driving a primary ciliopathy. Early, systemic treatment with SMN-restoring therapies is likely to be required to target neurodevelopmental comorbidities.

2025-09-01 | GSE295681 | GEO

Gene expression profiling of LMC and MMC motor neurons in SMA mice

Project description:Spinal muscular atrophy (SMA) is a neurodegenerative disease which exhibits selective motor neuron death caused by a ubiquitous deficiency of the survival motor neuron (SMN) protein. It remains unclear how the ubiquitous reduction of SMN lead to death in selective motor neuron pools. Medial motor neuron columns (MMC) are vulnerable, whereas lateral motor columns (LMC) are resistant to motor neuron death in SMA. Here we performed microarray and pathway analysis comparing cholera toxin subunit B (CTb) labeled vulnerable MMC and resistant LMC of pre-symptomatic SMA with corresponding motor neuron columns of control mice to identify pathways involved in selective motor neuron death in SMA. WT is FVB. SMN is Delta7 (SMNΔ7;SMN2;Smn-) on a FVB background.

2017-12-12 | GSE81245 | GEO

The Bap1-SMN axis in Dpp4+ skeletal muscle mesenchymal cells regulates survival of motor neurons

Project description:Spinal muscular atrophy (SMA) is a neuromuscular disease caused by mutations in the survival of motor neuron (SMN) gene. Although the primary manifestation of SMA is degeneration of motor neurons in a dying-back manner, deficient SMN intrinsic to motor neurons does not cause severe motor neuron loss, as is the case in SMA mouse models. Thus, the involvement of non-neuronal cells in the pathogenesis of SMA has been suggested. Here, we report that a novel subset of fibro-adipogenic progenitors expressing Dpp4 (Dpp4+ FAPs) is required for the survival of motor neurons, in which BRCA1-associating protein 1 (Bap1) is crucial for the stabilization of SMN by preventing its ubiquitination-dependent degradation. Inactivation of Bap1 in FAPs decreased SMN levels and accompanied degeneration of the neuromuscular junction, leading to dying-back loss of motor neurons and muscle atrophy, reminiscent of SMA pathogenesis. Overexpression of ubiquitination-resistant SMN variant, SMNK186R, in Bap1-null FAPs completely prevented neuromuscular degenerations. In addition, transplantation of Dpp4+ FAPs, but not Dpp4- FAPs, completely rescued neuromuscular defects in the mutant mice. Our data revealed that Bap1-mediated stabilization of SMN in Dpp4+ FAPs is crucial for the survival of motor neurons and provided a new therapeutic approach to treat SMA.

2022-06-30 | GSE190426 | GEO

The small-molecule flunarizine in spinal muscular atrophy patient fibroblasts impacts on the Gemin components of the SMN complex and RNA-binding proteins relevant to motor neuron diseases

Project description:The deficiency of Survival motor neuron (SMN) protein causes the motor neuron disease spinal muscular atrophy (SMA). One of the cellular hallmarks of motor neuron diseases is the reduction in number of nuclear bodies (NBs) positive for the SMN protein. Owing to its ubiquitous expression, the consequences of SMN reduction can be studied in SMA patient fibroblasts. In previous studies, we described the beneficial effects of flunarizine on SMN-positive NBs both in fibroblasts of SMA patients and in spinal motor neurons of an SMA mouse model. Given that nuclear bodies are involved in RNA metabolism, here the goals are to make a proof-of-concept that genes modulated by flunarizine at the RNA levels can be identified and confirmed at the protein levels in SMA patient fibroblasts. Indeed, RNA-Seq analysis reveals that TXNIP is the most reduced by a 4-hr flunarizine treatment of SMA patient fibroblasts. This result is confirmed by RT-qPCR. Moreover, immunoblot analyses also shows a marked reduction of TXNIP at the protein levels in flunarizine-treated SMA fibroblasts.

2020-04-30 | GSE145146 | GEO

Ribosome profiling of SMN-primed ribosomes and active ribosome profiling from brains of a mouse model of severe SMA

Project description:Spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality, with an incidence of around 1 in 6,000-10,000 live births. SMA is caused by low levels of full-length survival of motor neuron protein (SMN). We demonstrate that SMN binds to ribosomes and that this interaction is tissue-dependent. We performed ribosome profiling analyses on lysates from P5 wild-type mouse brains exposed to RNase I, from which we isolated SMN-primed ribosomes by immunoprecipitation. SMN-primed ribosomes are preferentially positioned within the first five codons of a set of mRNAs which are enriched for translational enhancer sequences in the 5’UTR and rare codons at the beginning of their coding sequence. These SMN-specific mRNAs are associated with neurogenesis, lipid metabolism, ubiquitination, chromatin regulation and translation. Additionally, we analyzed the positioning of active ribosomes using the Active-RiboSeq method based on RiboLace and compared early symptomatic SMA mouse brains to age-matched controls. We found that loss of SMN induces ribosome depletion, especially at the beginning of the coding sequence of SMN-specific mRNAs, leading to impairment of proteins involved in motor neuron function and stability. Keywords: motor neuron disease, spinal muscular atrophy, SMA, SMN, SMN1, survival of motor neuron, SMN-primed ribosome profiling, translation, RiboLace, Ribo-Seq, active translation, ribosome heterogeneity

2020-08-11 | GSE154106 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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