Microarray expression profiling in zebrafish rnaset2 mutant
Ontology highlight
ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE138493 | GEO | 2019/10/08
REPOSITORIES: GEO
Similar Datasets
Project description:Infantile-onset RNaseT2 deficient leukoencephalopathy is characterised by cystic brain lesions, multifocal white matter alterations, cerebral atrophy, and severe psychomotor impairment. The phenotype is indistinguishable from congenital cytomegalovirus brain infection and overlaps with typeI interferonopathies like Aicardi-Goutières syndrome, strongly suggesting a role for innate immunity in its pathophysiology. To date, pathophysiological studies have been hindered by the lack of mouse models recapitulating the neuroinflammatory encephalopathy found in patients. In this study, we generated Rnaset2-/- mice using CRISPR/Cas9-mediated genome editing. Strikingly, Rnaset2-/- mice revealed strong upregulation of interferon-stimulated genes and concurrent neuroinflammation, with infiltration of CD8+ effector memory T cells and inflammatory monocytes into the grey and white matter. Homeostatic dysfunctions in glia cells and neurons revealed by single nuclei RNA sequencing provides initial insights into the mechanism of hippocampal-accentuated brain atrophy and cognitive impairment. Thus, Rnaset2 -/- mice provide an important model, to develop therapies for inborn RNaseT2 deficiency, congenital viral brain infection and further type I interferonopathies.
2021-09-30 | GSE180138 | GEO
Project description:Microarray expression profiling in zebrafish rnaset2 mutant
| PRJNA576178 | ENA
Project description:Hey3Met2 cells were stably transfected with plasmids encoding either wild-type RNASET2 or a catalytically dead form (whose cDNA has been previously mutagenized in the two CAS catalytic sites) or with the empty vector as a control. The control of ovarian tumorigenesis by RNASET2 occurs through modification of the cellular microenvironment and involvement of immunocompetent cells, thus providing evidence for specific modulations of cellular responses induced by RNASET2 that might underlay ovarian tumorigenesis. In order to get more inside on the effect of RNASET2 on the modulation of other genes, a whole genome expression has been run on Hey3Met2 cell transfected with wildtype or mutated RNASET2. Hey3Met2 human ovarian cancer cells were transfected with espression vectors encoding either wild type or catalitycally dead mutant RNASET2. Clones transfected with the empty vectors were used as negative controls. Three independent clones were used for the each type of transfected plasmid.
2011-06-01 | E-GEOD-28478 | biostudies-arrayexpress
Project description:To investigate the molecular pathways underlying RNASET2-mediated tumor suppression in vivo, we investigated the gene expression profile of tumor samples obtained from control and RNASET2-silenced OVCAR3 xenografts, respectively. In order to evaluate the contribution of human cancer cells and the murine host stroma to RNASET2-mediated tumorigenesis responses, total RNA extracted from tumor xenografts derived from six independent OVCAR3 cell clones (three parental and three RNASET2-silenced clones) was fluorescently labeled and hybridized to human Agilent whole-genome microarrays.
2013-05-01 | GSE43029 | GEO
Project description:Hey3Met2 cells were stably transfected with plasmids encoding either wild-type RNASET2 or a catalytically dead form (whose cDNA has been previously mutagenized in the two CAS catalytic sites) or with the empty vector as a control. The control of ovarian tumorigenesis by RNASET2 occurs through modification of the cellular microenvironment and involvement of immunocompetent cells, thus providing evidence for specific modulations of cellular responses induced by RNASET2 that might underlay ovarian tumorigenesis. In order to get more inside on the effect of RNASET2 on the modulation of other genes, a whole genome expression has been run on Hey3Met2 cell transfected with wildtype or mutated RNASET2.
2011-06-01 | GSE28478 | GEO
Project description:To investigate the molecular pathways underlying RNASET2-mediated tumor suppression in vivo, we investigated the gene expression profile of tumor samples obtained from control and RNASET2-silenced OVCAR3 xenografts, respectively. In order to evaluate the contribution of human cancer cells and the murine host stroma to RNASET2-mediated tumorigenesis responses, total RNA extracted from tumor xenografts derived from six independent OVCAR3 cell clones (three parental and three RNASET2-silenced clones) was fluorescently labeled and hybridized to human Agilent whole-genome microarrays. Control and RNASET2-silenced OVCAR3 were injected subcutaneously into nude mice. After 39 days mice were sacrified, tumors were extracted and total RNA purified.
2013-05-01 | E-GEOD-43029 | biostudies-arrayexpress
Project description:The cystic leukoencephalopathy without megalencephaly has been defined as distinct autosomal-recessive syndrome of quasi-static encephalopathy with normo- or microcephaly, impaired psychomotor development and characteristic pattern on brain MRI. We identified mutations in the gene encoding the RNASET2 glycoprotein in seven affected individuals as the cause of disease. The results suggest that RNASET2 plays an important role in central nervous system myelination and development.
2009-06-02 | GSE11964 | GEO
Project description:Background & Aims Variants in the tumor necrosis factor superfamily member 15 gene (TNFSF15, also called TL1A) have been associated with risk for inflammatory bowel diseases (IBD). TL1A affects expression of multiple cytokines to promote mucosal inflammation. Little is known about the TL1A-response pathways that regulate cytokine expression. We investigated T-cell gene expression patterns to determine the mechanisms by which TL1A regulates cytokine production, and whether these associate with outcomes of patients with Crohn’s disease (CD).Methods Peripheral T cells isolated from normal donors were cultured with TL1A. We performed gene expression profile analysis, by RNA sequencing, of subsets of interferon gamma (IFNG)-producing and non-producing cells, purified by flow cytometry. Unsupervised hierarchical clustering analysis was used to identify gene expression differences between these subsets. Ribonuclease T2 gene (RNASET2) expression and methylation were assessed by quantitative trait loci analyses. Clinical characteristics of patients (complications, resistance to therapy, recurrence time) were associated with single nucleotide polymorphisms in RNASET2. We performed motif screening to identify polymorphisms that disrupt transcription factor binding sites. Levels of RNASET2 were knocked down with small interfering RNA in CD4+ T cells and the effect on protein expression was determined by proteomic analysis and cytokine production. Cell aggregation was measured by flow cytometry. ResultsWe identified 764 genes with at least a 2-fold difference in TL1A-mediated expression between IFNG-secreting and non-secreting T cells (P<1 × 10−5). Many of these genes were located near IBD susceptibility variants. RNASET2 was the only IBD risk-associated gene with greater than 5-fold downregulation in the IFNG-secreting subset. RNASET2 disease risk variants were associated with decreased expression in peripheral and mucosal tissues and DNA hypermethylation in CD patients requiring surgical intervention. RNASET2 disease risk variants were associated in CD patients with more complicated disease or resistance to therapy, defined in part by failed response to treatment, increased length of intestinal resection, shorter time to repeat surgery, and high Rutgeerts score (>2) in post-operative endoscopy. The RNASET2 variant rs2149092 was predicted to disrupt a consensus binding site for the transcription factor ETS within an enhancer region. Expression of RNASET2 correlated with expression of ETS. RNASET2 knockdown in T cells increased expression of IFNG and ICAM1 and induced T cells aggregation. A blocking antibody against LFA1, disrupting the LFA1-ICAM1 interaction, reduced T-cell production of IFNG. Conclusions We identified decreased expression of RNASET2 as a component of TL1A-mediated increase in production of IFNG and as a potential biomarker for patients with severe CD. Further study of the role of RNASET2 in regulating mucosal inflammation may lead to development of novel therapeutic targets.
2022-10-11 | GSE215144 | GEO
Project description:The cystic leukoencephalopathy without megalencephaly has been defined as distinct autosomal-recessive syndrome of quasi-static encephalopathy with normo- or microcephaly, impaired psychomotor development and characteristic pattern on brain MRI. We identified mutations in the gene encoding the RNASET2 glycoprotein in seven affected individuals as the cause of disease. The results suggest that RNASET2 plays an important role in central nervous system myelination and development. 2-Color dye swap design independent for two different families including technical and biologial replicates for affected family members (disease) and not affected family members (controls).
2009-06-02 | E-GEOD-11964 | biostudies-arrayexpress
Project description:Vanishing white matter (VWM) is a leukodystrophy that primarily manifests in young children. In this disease, the brain white matter is differentially affected in a predictable pattern with telencephalic brain areas being more severely affected, while others remain allegedly completely spared. Using high-resolution mass spectrometry-based proteomics, we investigated the proteome patterns of the severely affected white matter in the frontal lobe and normal appearing pons in VWM and control cases to identify molecular bases underlying regional vulnerability. By comparing VWM patients to controls, we identified disease-specific proteome patterns. We showed substantial pathogenic changes in both the frontal white matter and pons at the protein level. Side-by-side comparison of brain region-specific proteome patterns further revealed regional differences. We found that different cell types are affected in the VWM frontal white matter than in the pons. Gene ontology and pathway analyses identified involvement of region distinct biological processes, of which pathways implicated in cellular respiratory metabolism were overarching features. In the VWM frontal white matter, proteome changes were associated with decrease in glycolysis/gluconeogenesis and metabolism of various amino acids. By contrast, in the VWM pons white matter, we found a decrease in oxidative phosphorylation. Taken together, our data show that brain regions are affected in parallel in VWM, but to different degrees. We found region-specific involvement of different cell types and discovered that cellular respiratory metabolism is differently affected across white matter regions in VWM. These region-specific changes help explain regional vulnerability to pathology in VWM.
2023-06-28 | PXD040861 | Pride