E-GEOD-37148
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA158425
PROVIDER: E-GEOD-37148 | ExpressionAtlas | 2015-09-28
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-GEOD-37148-analysis-methods.tsv | Tabular | |||
| E-GEOD-37148-atlasExperimentSummary.Rdata | Rdata | |||
| E-GEOD-37148-configuration.xml | Xml | |||
| E-GEOD-37148-percentile-ranks.tsv | Tabular | |||
| E-GEOD-37148.condensed-sdrf.tsv | Tabular |
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Project description:Transcriptome Profiling following Neuronal and Glial Expression of ALS-linked SOD1 in Drosophila
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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:In this study we investigated the role of SRSF1 in mitigating locomotor defect in C9ORF72-ALS/FTD Drosophila lines. We analysed the transcriptomes of Drosophila heads from the same lines: (i) control flies expressing 3 G4C2 repeats and a luciferase-RNAi control (G4C2x3 + C-RNAi); (ii) C9ORF72-ALS/FTD model expressing 36 G4C2 repeats and the RNAi control (G4C2x36 + C-RNAi); (iii) C9ORF72-ALS/FTD-neuroprotected flies expressing 36 G4C2 repeats and the disrupted SRSF1 allele (G4C2x36 + ΔSRSF1). RNA samples were profiled using Drosophila 3' IVT gene expression Affymetrix microarrays prior to qRT-PCR validation of the SRSF1 depletion in neuroprotected flies. This study is part of a larger study that investigates the mitigating role of SRSF1 at whole-genome level to detect transcriptomal alterations and neuronal hyperexcitability in C9ORF72-linked amyotrophic lateral sclerosis.
2021-07-21 | GSE138592 | GEO
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:Pathogenic variants in WDFY3, a gene encoding for an autophagy adaptor termed ALFY, are linked to neurodevelopmental delay and altered brain size in human probands. While the role of WDFY3 loss-of-function is extensively studied in neurons, little is known about the effects of WDFY3 upregulation in different cell types of the central nervous system (CNS). We show that overexpression of the Drosophila melanogaster WDFY3 ortholog, Bchs, in either glia or neurons impaired autophagy and locomotion. Bchs glial overexpression also increased VNC size and glial nuclei number significantly, whereas neuronal Bchs overexpression affected wing and thorax morphology. We identified 79 genes that were differentially expressed and overlapped in flies that overexpress Bchs in glial and neuronal cells, respectively. Additionally, upon neuronal Bchs overexpression differentially expressed genes clustered in gene ontology categories associated with autophagy and mitochondrial function. Our data indicate that glial as well as neuronal Bchs upregulation can have detrimental outcomes on neural function.
2025-02-04 | GSE244775 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE40649: Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs (microarray) GSE40651: Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs (CLIP-Seq) GSE40652: Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs (RNA-Seq) Refer to individual Series
2012-09-30 | E-GEOD-40653 | biostudies-arrayexpress
Project description:Chronic activation of glial cells leads to the dysfunction and degeneration of motor and cortical neurons in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) with an unknown mechanism. To shed light on the molecular pathogenetic processes underlying the exordium and contribution of gliosis to disease onset and progression, we used cells, mice, and patient-derived cells modeling TDP-43, SOD1, and C9orf72-linked and sporadic ALS. Our data reveal a sequential disease progression, starting with enhanced glial reactivity and proliferation, and transitioning into inflammation with upregulation of pro-inflammatory genes. Using mouse genetics, we show that expression of mutant TDP-43 in astrocytes is necessary to cause gliosis and behavioral abnormalities. Mechanistically, we show that glial MYC gain-of-function drives neurodegeneration by promoting the release of astrocytic EVs that nonetheless fail to provide trophic support to surrounding neurons. Our research reveals a novel functional role for MYC in glia-to-neuron miscommunication in ALS.
2025-11-20 | GSE275841 | GEO
Project description:Several RNA-binding proteins (RBPs) are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), including the FET proteins FUS, TAF15 and EWSR1. Cabeza (caz) is the single Drosophila FET ortholog. Here, we identified Xrp1, a poorly characterized DNA-binding protein, as a key modifier of caz mutant phenotypes. Xrp1 expression was strongly upregulated in caz mutants, and Xrp1 heterozygosity rescued their motor defects and life span. Interestingly, selective neuronal Xrp1 knock-down was sufficient to rescue, and neuronal Xrp1 overexpression phenocopied caz mutant phenotypes. The caz/Xrp1 genetic interaction depended on the functionality of the AT-hook DNA-binding domain in Xrp1. Consistently, caz mutants displayed gene expression dysregulation, which was mitigated by Xrp1 heterozygosity. Finally, Xrp1 knock-down substantially rescued the motor deficits and life span of flies expressing ALS-mutant FUS in motor neurons. Taken together, caz mutant phenotypes are mediated by increased neuronal Xrp1 levels, leading to gene expression dysregulation and neuronal dysfunction.
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Project description:Functional abnormality of TAR DNA-binding protein 43 (TDP-43), an aggregation-prone RNA and DNA binding protein, is observed in the vast majority of both familial and sporadic ALS cases and in ~40% of FTLD cases, but the cascade of events leading to cell death are not understood. We have expressed human TDP-43 (hTDP-43) in Drosophila neurons and glia, a model that recapitulates many of the characteristics of TDP-43-linked human disease including protein aggregation pathology, locomotor impairment, and premature death. We report that such expression of hTDP-43 impairs small interfering RNA (siRNA) silencing, which is the major post-transcriptional mechanism of retrotransposable element (RTE) control in somatic tissue. This is accompanied by de-repression of a panel of both LINE and LTR families of RTEs, with somewhat different elements being active in glia vs neurons. hTDP-43 expression in glia causes an early and severe loss of control of a specific RTE, the endogenous retrovirus (ERV) gypsy. We demonstrate that gypsy causes the degenerative phenotypes in these flies because we are able to rescue the toxicity of glial hTDP-43 either by genetically blocking expression of this RTE or by pharmacologically inhibiting RTE reverse transcriptase activity. Moreover, we provide evidence that activation of DNA damage-mediated programmed cell death underlies both neuronal and glial hTDP-43 toxicity, consistent with RTE-mediated effects in both cell types. Our findings suggest a novel mechanism in which RTE activity contributes to neurodegeneration in TDP-43-mediated diseases such as ALS and FTLD.
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