Gene network landscape of murine splenocytes reveals integrin as the A151 ODN-responsive hub in immune transcriptome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA767337 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:PURPOSE: Homeostatic restoration of an inflammatory response requires quenching of the immune system after pathogen threats vanish. A continued assault orchestrated by host defense results in tissue destruction or autoimmunity. A151 is the epitome of synthetic oligodeoxynucleotides (ODNs) that curb immune response by a subset of white corpuscles through repetitive telomere derived TTAGGG sequences. Nevertheless, the genuine effect A151 has on immune cell transcriptome still remains unknown. METHODS: We leveraged an integrative approach in which weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis of our in-house microarray data sets aided our understanding of how A151 ODN suppresses immune response in mouse splenocytes. We fed raw gene expression data from two different (scrambled ODN and A151 ODN) treatment groups with a varying number of replicate arrays (29 and 16, respectively) into WGCNA, limma, and GSEA separetely to understand different dimensions of the A151 ODN-driven immune modulation at the transcriptome level. RESULTS: Together with experimental and in silico validations, we demonstrated that A151 ODN acts on components of integrin complexes, namely Itgam and Itga6, to interfere with immune cell adhesion, and thereby, suppress the immune response in mouse. Furthermore, we revealed that cell adhesion by integrin complexes serves as a focal point for cellular response to A151 ODN treatment in immune cells. CONCLUSION: A refined set of co-hub genes led by Itgam and Itga6 plays a pivotal role in A151 ODN-driven suppression of immune response. Also, A151 ODN treatment appears to interfere with immune cell adhesion to quench immune response in mouse splenocytes. The outcome of this study sheds light on the molecular basis of immune suppression by a clinically useful DNA-based therapeutic agent and may open new revenues for A151 ODN research.
2021-10-01 | GSE184994 | GEO
Project description:Integrins are among the most abundant cell surface receptors constituting the principal adhesion receptors for the extracellular matrix (ECM), providing a physical anchor for the cell and triggering multiple intracellular signalling events. Loss-of function mutations of the integrin α3 gene (ITGA3) have been recently disclosed in patients with interstitial lung disease, congenital nephrotic syndrome and junctional epidermolysis bullosa, a multiorgan disorder with fatal outcome. In these patients, the respiratory function is strongly impaired and the kidneys are variably affected, whereas skin fragility is rather mild, has a delayed onset after birth or remains unrecognized, suggesting that integrin α3 differently influences the development and homeostasis of these organs. Here we employed authentic human keratinocytes bearing a naturally occurring integrin α3 loss-of-function mutation as a prototype to characterize the molecular mechanisms launched by the constitutional absence of this integrin subunit. To validate our findings, we generated new cellular models, including an additional ILNEB patient cell line, ITGA3 rescued and knockdown cells. We show that keratinocytes lacking a functional α3 subunit have an activated cellular phenotype with a switch in the pattern of integrin α subunits on the cell surface. These assure spreading and adhesion of epidermal keratinocytes but also drive the migratory phenotype of these cells.
2017-03-16 | GSE75838 | GEO
Project description:Microarray analysis was used to identify the differentially expressed genes. Bioinformatics analyses integrated with databases and text-mined gene network were conducted to understand irradiation-related hub genes, pathways and biological processes. Our hypothesis in these paper are: 1) the expression profiles of irradiation damaged bone marrow tissue are not identical in injury phase and recovery phase; and 2) some hub genes potentially vital to BM recovery can be screened out by means of microarray analysis and bioinformatics analysis. The results provide basic information to explain the radiation-related biological processes and hub genes. The five mRNA samples in total bone marrow cells were profiled by using gene chip at 3, 7, 11 and 21 days after irradiation and 0 day (sham-irradiation) as control. Each time point contains one sample.
2013-06-17 | E-GEOD-28195 | biostudies-arrayexpress
Project description:Cells treated with a specific antibody against α5β1 integrin exhibited cell spreading and scattering, over-expression of liver stem/progenitor cell markers and activation of the ERK1/2 and p38 MAPKs signaling cascades, in a similar manner to the process triggered by HGF/SF1 stimulation. Gene expression profiling revealed marked transcriptional changes of genes involved in cell adhesion and migration, as well as genes encoding chromatin remodeling factors. These responses were accompanied by conspicuous spatial reorganization of centromeres, while integrin genes conserved their spatial positioning in the interphase nucleus. Untreated cells versus HGF/SF1 treated or α5β1 integrin-mediated cell migration
2010-08-26 | E-GEOD-23853 | biostudies-arrayexpress
Project description:To explore TNF-related genes in GPI-induced arthritis, we performed GeneChip analysis using arthritic splenocytes and control-immunized splenocytes. Among the arrayed TNFalpha-related genes, TIARP mRNA was highly expressed in arthritic splenocytes, with levels exceeding more than 20-times the control splenocytes
2009-07-24 | GSE17272 | GEO
Project description:It has been difficult to elucidate the structure of gene regulatory networks under anticancer drug treatment. Here, we developed an algorithm to highlight the hub genes that play a major role in creating the upstream and downstream relationships within a given set of differentially expressed genes. The directionality of the relationships between genes was defined using information from comprehensive collections of transcriptome profiles after gene knockdown and overexpression. As expected, among the drug-perturbed genes, our algorithm tended to derive plausible hub genes, such as transcription factors. Our validation experiments successfully showed the anticipated activity of certain hub gene in establishing the gene regulatory network that was associated with cell growth inhibition. Notably, giving such top priority to the hub gene was not achieved by ranking fold change in expression and by the conventional gene set enrichment analysis of drug-induced transcriptome data. Thus, our data-driven approach can facilitate to understand drug-induced gene regulatory networks for finding potential functional genes.
2018-05-22 | GSE104175 | GEO
Project description:Lymphocytes are adversely affected during sepsis. Some CD4+ splenocytes undergo apoptosis while others become Th2 polarized. The molecular determinants of these phenotypic changes are not known. Here we compare the transcriptional response of septic CD4 splenocytes to CD4 splenocytes from sham-manipulated animals 6h after sepsis and identify an early transcriptional component to the septic CD4+ splenocyte phenotype. We used microarrays to detail the global program of gene expression underlying the sepsis-induced changes in CD4+ splenocyte phenotype. Keywords: disease state analysis
2006-06-01 | GSE4479 | GEO
Project description:Geier2011 - Integrin activation
Rule based model that integrates the available data to test the biololical hypotheses regarding the role of talin, Dok1 and PIPKI in integrin activation.
This model is described in the article:
A computational analysis of the dynamic roles of talin, Dok1, and PIPKI for integrin activation.
Geier F, Fengos G, Iber D.
PLoS One. 2011;6(11):e24808.
Abstract:
Integrin signaling regulates cell migration and plays a pivotal role in developmental processes and cancer metastasis. Integrin signaling has been studied extensively and much data is available on pathway components and interactions. Yet the data is fragmented and an integrated model is missing. We use a rule-based modeling approach to integrate available data and test biological hypotheses regarding the role of talin, Dok1 and PIPKI in integrin activation. The detailed biochemical characterization of integrin signaling provides us with measured values for most of the kinetics parameters. However, measurements are not fully accurate and the cellular concentrations of signaling proteins are largely unknown and expected to vary substantially across different cellular conditions. By sampling model behaviors over the physiologically realistic parameter range we find that the model exhibits only two different qualitative behaviors and these depend mainly on the relative protein concentrations, which offers a powerful point of control to the cell. Our study highlights the necessity to characterize model behavior not for a single parameter optimum, but to identify parameter sets that characterize different signaling modes.
This model is hosted on BioModels Database
and identified
by: MODEL1208280001
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2014-03-05 | MODEL1208280001 | BioModels
Project description:Effect of c-fos expression in osteoclastogenic splenocytes. Keywords: other
2004-09-19 | GSE676 | GEO
Project description:Identification of imprinted genes expressed in adult CD3+ splenocytes Experiment Overall Design: For analysis of imprinted gene expression of uniparental-derived cells in adult recipients we chose eGFP/CD3-double positive splenocytes as a defined cell type, and first identified imprinted genes that are normally expressed in this cell type by microarray analysis of normal eGFP/CD3-double positive splenocytes from an eGFP transgenic B6129 mouse.
2008-06-15 | E-GEOD-6757 | biostudies-arrayexpress