Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-Seq data from V321L mouse dentate gyrus (DG)

ABSTRACT: Schizophrenia is a complex genetic neurodevelopmental disorder. eQTLs form bulk of the genetic variation contributing to schizophrenia. However, there is no known mechanism explaining regulation of expression of eQTL associated risk genes and underlying neurodevelopmental processes that are part of the cellular pathology. Neuregulin1-ErbB4 signaling plays a crucial role in synaptogenesis and has been implicated in schizophrenia. Gamma secretase mediated NRG1 nuclear back-signaling is thought to be involved in transcriptional regulation. A psychosis-associated missense mutation in NRG1 (rs74942016) has been predicted to impair nuclear back-signaling thereby implicating this mode of signaling in the underlying cellular pathology.

ORGANISM(S): Mus musculus

PROVIDER: GSE192869 | GEO | 2023/12/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Quantitative phosphoproteomics analysis of ERBB3/ERBB4 signaling

Project description:The four members of the epidermal growth factor receptor (EGFR/ERBB) family form homo- and heterodimers which mediate ligand-specific regulation of many key cellular processes in normal and cancer tissues. While signaling through the EGFR has been extensively studied on the molecular level, signal transduction through ERBB3/ERBB4 heterodimers is less well understood. Here, we generated isogenic mouse Ba/F3 cells that express full-length and functional membrane-integrated ERBB3 and ERBB4 or ERBB4 alone, to serve as a defined cellular model for biological and phosphoproteomics analysis of ERBB3/ERBB4 signaling. ERBB3 co-expression significantly enhanced Ba/F3 cell proliferation upon neuregulin-1 (NRG1) treatment. For comprehensive signaling studies we performed quantitative mass spectrometry (MS) experiments to compare the basal ERBB3/ERBB4 cell phosphoproteome to NRG1 treatment of ERBB3/ERBB4 and ERBB4 cells. We employed a workflow comprising differential isotope labeling with mTRAQ reagents followed by chromatographic peptide separation and final phosphopeptide enrichment prior to MS analysis. Overall, we identified 9686 phosphorylation sites which could be confidently localized to specific residues. Statistical analysis of three replicate experiments revealed 492 phosphorylation sites which were significantly changed in NRG1-treated ERBB3/ERBB4 cells. Bioinformatics data analysis recapitulated regulation of mitogen-activated protein kinase and Akt pathways, but also indicated signaling links to cytoskeletal functions and nuclear biology. Comparative assessment of NRG1-stimulated ERBB4 Ba/F3 cells indicated that ERBB3 did not trigger defined signaling pathways but more broadly enhanced phosphoproteome regulation in cells expressing both receptors. In conclusion, our data provide the first global picture of ERBB3/ERBB4 signaling and provide numerous potential starting points for further mechanistic studies

2016-01-15 | PXD002665 | Pride

Investigating genes regulated by Nrg1 nuclear back signaling.

Project description:Investigating genes regulated by Nrg1 nuclear back signaling.

| PRJNA1119194 | ENA

The Role of Endothelial Autocrine NRG1/ERBB4 Signaling in Cardiac Remodeling

Project description:Neuregulin-1 (NRG1) is a paracrine growth factor, secreted by cardiac endothelial cells (Ecs) in conditions of cardiac overload/injury. The current concept is that the cardiac effects of NRG1 are mediated by activation of ERBB4/ERBB2 receptors on cardiomyocytes. However, recent studies have shown that paracrine effects of NRG1 on fibroblasts and macrophages are equally important. Here, we hypothesize that NRG1 autocrine signaling plays a role in cardiac remodeling. We generated EC–specific Erbb4 knockout mice to eliminate endothelial autocrine ERBB4 signaling without affecting paracrine NRG1/ERBB4 signaling in the heart. We first observed no basal cardiac phenotype in these mice up to 32 weeks. We next studied these mice following transverse aortic constriction (TAC), exposure to angiotensin II (Ang II) or myocardial infarction in terms of cardiac performance, myocardial hypertrophy, myocardial fibrosis and capillary density. In general, no major differences between EC–specific Erbb4 knockout mice and control littermates were observed. However, 8 weeks following TAC both myocardial hypertrophy and fibrosis were attenuated by EC–specific Erbb4 deletion, albeit these responses were normalized after 20 weeks. Similarly, 4 weeks after Ang II treatment myocardial fibrosis was less pronounced compared to control littermates. These observations were supported by RNA-sequencing experiments on cultured endothelial cells showing that NRG1 controls the expression of various hypertrophic and fibrotic pathways. Overall, this study shows a role of endothelial autocrine NRG1/ERBB4 signaling in the modulation of hypertrophic and fibrotic responses during early cardiac remodeling. This study contributes to understanding the spatio-temporal heterogeneity of myocardial autocrine and paracrine responses following cardiac injury.

2020-05-15 | GSE150619 | GEO

Nrg1/ErbB4 signaling contributes to the effects of the ketogenic diet on GABAergic activity and seizures

Project description:The ketogenic diet (KD) has been used as an effective therapy to treat epilepsy. Previous studies indicate an elevated level of GABA in the brain by KD treatment. However, the underlying mechanisms remain to be elucidated. Here we report that KD treatment suppresses seizures in both acute and chronic seizure models and enhances presynaptic GABA release probability in the hippocampus. By screening molecular targets that potentially linked to GABAergic activity with transcriptome analysis, we identify that KD treatment dramatically increased the Nrg1 gene expression in the hippocampus. Disruption of Nrg1 signaling by genetically deleting its receptor-ErbB4 or blocking ErbB4 kinase activity abolishes KD’s effects on GABAergic activity and seizures. Mechanistically, KD treatment increases Nrg1 expression via up-regulating histone acetylation. Our findings suggest a critical role of Nrg1/ErbB4 signaling in mediating KD’s effects on GABAergic activity and seizures, which sheds light on the development of new therapeutic interventions to seizure control.

2020-08-24 | GSE156687 | GEO

Gene Expression Profiling on Stably Expressing Full Length (FL) JM-a CYT-1 or CYT-2 ERBB4 isoforms in MCF10A cells

Project description:Convergent and divergent effects of two FL ERBB4 isoforms on gene expression in normal-like MCF10A mammary epithelial cells lacking endogeneous ERBB4 expression. Control vector (VEC) and ERBB4 expression MCF10A cells(CYT1 or CYT2) were serum starved for 48 hours and incubated with or without ERBB4 ligand NRG1 for 2h. RNA samples were collected and analyzed.

2014-05-07 | E-GEOD-57346 | biostudies-arrayexpress

Small-Molecule-Induced ERBB4 Activation to Treat Heart Failure

Project description:To determine the transcriptomic changes of small-molecule-induced activation of ERBB4 in heart failure, we tested the effects of the two small molecules (NRG1 and EF-1) of ERBB4 agonists on iAM (immortalized atrial cardiomyocytes) model. The transcriptional profiles of mRNA in these samples will be measured with high throughput technology. Changes in transcriptional profiles between the activation of EF-1 and NRG1 will be compared.

2024-11-13 | GSE256024 | GEO

Small-Molecule-Induced ERBB4 Activation to Treat Heart Failure

Project description:To determine the transcriptomic changes of small-molecule-induced activation of ERBB4 in heart failure, we tested the effects of the two small molecules (NRG1 and EF-1) of ERBB4 agonists on the HCF (human cardiac fibroblasts) model. The transcriptional profiles of mRNA in these samples will be measured with high throughput technology. Changes in transcriptional profiles between the activation of EF-1 and NRG1 will be compared.

2024-11-13 | GSE261219 | GEO

The Role of Endothelial Autocrine NRG1/ERBB4 Signaling in Cardiac Remodeling

Project description:The Role of Endothelial Autocrine NRG1/ERBB4 Signaling in Cardiac Remodeling

| PRJNA632924 | ENA

Hippocampal Subfield Transcriptome Analysis in Schizophrenia Psychosis

Project description:We have previously demonstrated functional and molecular changes in hippocampal subfields in individuals with schizophrenia (SZ) psychosis associated with hippocampal excitability. In this study, we use RNA-seq and assess global transcriptome changes in the hippocampal subfields, DG, CA3, and CA1 from individuals with SZ psychosis and controls to elucidate subfield-relevant molecular changes. We also examine changes in gene expression due to antipsychotic medication in the hippocampal subfields from our SZ ON- and OFF-antipsychotic medication cohort. We identify unique subfield-specific molecular profiles in schizophrenia postmortem samples compared to controls, implicating astrocytes in DG, immune mechanisms in CA3, and synaptic scaling in CA1. We show a unique pattern of subfield-specific effects by antipsychotic medication on gene expression levels with scant overlap of genes differentially expressed by SZ disease effect versus medication effect. These hippocampal subfield changes could provide the basis for previously observed hippocampal SZ pathology and explain the lack of full efficacy of conventional antipsychotic medication on SZ symptomatology. With further characterization, the identified distinct molecular profiles of the DG, CA3, and CA1 in SZ psychosis may serve to identify potential hippocampal-based therapeutic targets.

2020-05-11 | GSE138082 | GEO

Diurnal alterations in gene expression across striatal subregions in psychosis

Project description:Background: Psychosis is a defining feature of schizophrenia and highly prevalent in bipolar disorder. Notably, individuals suffering with these illnesses also have major disruptions in sleep and circadian rhythms, and disturbances to sleep and circadian rhythms can precipitate or exacerbate psychotic symptoms. Psychosis is associated with the striatum, though no study to date has directly measured molecular rhythms and determined how they are altered in the striatum of subjects with psychosis. Methods: Here, we perform RNA-sequencing and both differential expression and rhythmicity analyses to investigate diurnal alterations in gene expression in human postmortem striatal subregions (NAc, caudate, and putamen) in subjects with psychosis relative to unaffected comparison subjects. Results: Across regions, we find differential expression of immune-related transcripts and a substantial loss of rhythmicity in core circadian clock genes in subjects with psychosis. In the nucleus accumbens (NAc), mitochondrial-related transcripts have decreased expression in psychosis subjects, but only in those who died at night. Additionally, we find a loss of rhythmicity in small nucleolar RNAs and a gain of rhythmicity in glutamatergic signaling in the NAc of psychosis subjects. Between region comparisons indicate that rhythmicity in the caudate and putamen is far more similar in subjects with psychosis than in matched comparison subjects. Conclusions: Together, these findings reveal differential and rhythmic gene expression differences across the striatum that may contribute to striatal dysfunction and psychosis in psychotic disorders.

2022-08-31 | GSE202537 | 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