The Neuronal CCAAT/enhancer binding protein α mediates HIF-1α-induced inflammatory brain damage after ischemia
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE81919 | GEO | 2021/12/31
REPOSITORIES: GEO
Similar Datasets
Project description:The peri- and postmenopausal periods in women are associated with decreases in circulating estrogen levels, marked acceleration of age-related bone loss and increased risk of fracture. However, despite the clinical importance of postmenopausal bone loss, our molecular understanding of this process is incomplete. Here, we used co-expression network analysis to gain novel insight into the molecular mechanisms mediating bone loss in ovariectomized (OVX) mice, a model of human menopause. Expression profiles from intact and OVX mice from a panel of inbred strains were used to generate a co-expression network consisting of 29 modules. Genes in network module 25 were decreased by OVX in all strains. Module 25 was enriched for genes involved in the response to oxidative stress, a process known to be an upstream causal factor for OVX-induced bone loss. It was also found that module 25 homologs were co-expressed in human bone marrow and were enriched for genes with evidence of genetic association with bone mineral density (BMD) in women. Alpha synuclein (Snca) was the most highly connected “hub” genes in module 25 and its in vivo knockout resulted in a 40% reduction in OVX-induced bone loss. Furthermore, protection was associated with the targeted alteration of genes in specific network modules, including module 10. Our results identify a gene module associated with OVX-induced bone loss and demonstrate that Snca regulates ovariectomy-induced bone loss by controlling bone network dynamics.
2016-12-01 | GSE68303 | GEO
Project description:The peri- and postmenopausal periods in women are associated with decreases in circulating estrogen levels, marked acceleration of age-related bone loss and increased risk of fracture. However, despite the clinical importance of postmenopausal bone loss, our molecular understanding of this process is incomplete. Here, we used co-expression network analysis to gain novel insight into the molecular mechanisms mediating bone loss in ovariectomized (OVX) mice, a model of human menopause. Expression profiles from intact and OVX mice from a panel of inbred strains were used to generate a co-expression network consisting of 29 modules. Genes in network module 25 were decreased by OVX in all strains. Module 25 was enriched for genes involved in the response to oxidative stress, a process known to be an upstream causal factor for OVX-induced bone loss. It was also found that module 25 homologs were co-expressed in human bone marrow and were enriched for genes with evidence of genetic association with bone mineral density (BMD) in women. Alpha synuclein (Snca) was the most highly connected “hub” genes in module 25 and its in vivo knockout resulted in a 40% reduction in OVX-induced bone loss. Furthermore, protection was associated with the targeted alteration of genes in specific network modules, including module 10. Our results identify a gene module associated with OVX-induced bone loss and demonstrate that Snca regulates ovariectomy-induced bone loss by controlling bone network dynamics.
2016-12-01 | GSE68302 | GEO
Project description:A new subset of pulmonary NSCLC patients can be defined as negative for C/EBP alpha and positive for Bmi-1 expression, which are mimicked by our lung-specific C/EBP alpha null mice. Bmi-1 activity is required for both tumor initiation and maintenance in the C/EBP alpha null background and pharmacological inhibition of Bmi-1 exhibits anti-tumor effect. Overall, we show that C/EBP alpha is a tumor-suppressor gene in lung, and that Bmi-1 is involved in mediating the oncogenic process downstream of C/EBP alpha, implying that Bmi-1 inhibition may offer a therapeutic advantage for the subset of patients with low levels of C/EBP alpha expression.
2015-12-31 | GSE56935 | GEO
Project description:Alcohol consumption is known to lead to gene expression changes in the brain. After performing gene co-expression network analysis (WGCNA) of genome-wide mRNA and microRNA expressions in the Nucleus Accumbens (NAc) from subjects with alcohol dependence (AD) and matched controls six mRNA and three miRNA modules significantly correlated with AD after Bonferroni correction (adj. p? 0.05) were identified. Cell-type-specific transcriptome analysis revealed two of the mRNA modules to be enriched for neuronal specific marker genes and downregulated in AD, whereas the remaining four were enriched for astrocyte and microglial specific marker genes and were upregulated in AD. Using gene set enrichment analysis, the neuronal specific modules were enriched for genes involved in oxidative phosphorylation, mitochondrial dysfunction and MAPK signaling, while the glial-specific modules were enriched mostly for genes involved in processes related to immune functions, i.e. reactome cytokine signaling in immune system (all adj. p? 0.05). In the mRNA and miRNA modules, 461 and 25 candidate hub genes were identified, respectively. In contrast to the expected miRNAs’ biological functions, the correlation analyses between mRNA and miRNA hub genes revealed a significantly higher number of positive than negative correlations (chi-square p? 0.0001). At FDR? 0.1, integration of the mRNA and miRNA hubs genes expression with genome-wide genotypic data identified 591 cis-eQTLs and 62 cis-eQTLs for the mRNA and miRNA hubs, respectively. Adjusting for the number of tests, the mRNA cis-eQTLs were significantly enriched for AD GWAS signals in the Collaborative Study on Genetics of Alcohol (COGA) sample (adj. p=0.024), providing a novel biological role for these association signals. In conclusion, our study identified coordinated mRNA and miRNA co-expression changes in the NAc of AD subjects, and our genetic (cis-eQTL) analysis provides novel insights into the etiological mechanisms of AD. Tissue samples were received from the Australian Brain Donor Programs New South Wales Tissue Resource Centre, which is supported by The University of Sydney, National Health and Medical Research Council of Australia, Schizophrenia Research Institute, National Institute of Alcohol Abuse and Alcoholism, and the New South Wales Department of Health. Cases were excluded if they had an infectious disease (i.e. HIV/AIDS, hepatitis B or C, or Creutzfeldt-Jakob disease), an unsatisfactory agonal status determined from the circumstances surrounding the death, post-mortem delays >48 hours, or significant head injury. In addition to case status, age, sex, ethnicity, brain weight, brain pH, post-mortem interval (PMI), tissue hemisphere, clinical cause of death, blood toxicology at time of death, smoking status, neuropathology and liver pathology were also provided for each subject. MiRNA and mRNA expression in 18 matched case-control pairs (N=36) with sample RINs ?6 were assessed on the Affymetrix GeneChip® Human Genome U133A 2.0 (HG-U133A 2.0) and Affymetrix GeneChip miRNA 3.0 microarray.
2015-05-22 | E-GEOD-62699 | biostudies-arrayexpress
Project description:NMN is the direct precursor of the nicotinamide adenine dinucleotide (NAD+) and is considered a key component to increase NAD+ levels and mitochondrial activity in cells. In this study, based on transcriptome analysis, we showed that NMN alleviates poly(I:C)-induced inflammatory response in two types of human primary cell cultures, human pulmonary microvascular endothelial cells (HPMEC) and human coronary artery endothelial cells (HCAEC). The major inflammatory mediators including IL-6 and PARP family members are grouped into co-expressed gene modules and significantly down-regulated under NMN-dosage in poly(I:C)-induced conditions in both cell types. The Bayesian network analysis of module hub genes predicted common genes including eukaryotic translation initiation factor 1B (EIF1B) and distinct genes such as platelet-derived growth factor binding molecules in HCAEC, which potentially regulate the identified inflammation modules. These results have suggested the robust regulatory mechanism of NMN to alleviate inflammatory pathways, which may open up the possibility of a new role for NMN replenishment in chronic or acute inflammation treatment.
2023-07-09 | GSE233679 | GEO
Project description:Alcohol consumption is known to lead to gene expression changes in the brain. After performing gene co-expression network analysis (WGCNA) of genome-wide mRNA and microRNA expressions in the Nucleus Accumbens (NAc) from subjects with alcohol dependence (AD) and matched controls six mRNA and three miRNA modules significantly correlated with AD after Bonferroni correction (adj. p≤ 0.05) were identified. Cell-type-specific transcriptome analysis revealed two of the mRNA modules to be enriched for neuronal specific marker genes and downregulated in AD, whereas the remaining four were enriched for astrocyte and microglial specific marker genes and were upregulated in AD. Using gene set enrichment analysis, the neuronal specific modules were enriched for genes involved in oxidative phosphorylation, mitochondrial dysfunction and MAPK signaling, while the glial-specific modules were enriched mostly for genes involved in processes related to immune functions, i.e. reactome cytokine signaling in immune system (all adj. p≤ 0.05). In the mRNA and miRNA modules, 461 and 25 candidate hub genes were identified, respectively. In contrast to the expected miRNAs’ biological functions, the correlation analyses between mRNA and miRNA hub genes revealed a significantly higher number of positive than negative correlations (chi-square p≤ 0.0001). At FDR≤ 0.1, integration of the mRNA and miRNA hubs genes expression with genome-wide genotypic data identified 591 cis-eQTLs and 62 cis-eQTLs for the mRNA and miRNA hubs, respectively. Adjusting for the number of tests, the mRNA cis-eQTLs were significantly enriched for AD GWAS signals in the Collaborative Study on Genetics of Alcohol (COGA) sample (adj. p=0.024), providing a novel biological role for these association signals. In conclusion, our study identified coordinated mRNA and miRNA co-expression changes in the NAc of AD subjects, and our genetic (cis-eQTL) analysis provides novel insights into the etiological mechanisms of AD.
2015-05-22 | GSE62699 | GEO
Project description:Recent research has shown that peripheral treatment with amylin reduces Alzheimer’s disease (AD) pathology in the brain and improves learning and memory in AD mouse models. To understand the mechanism underlying this novel treatment for AD, we interrogated the transcriptome for changes in cortical gene expression in amyloid precursor protein (APP) transgenic mice treated with amylin compared to a vehicle treated group and wild type (WT) mice. Using weighted gene co-expression network analysis, we discovered that amylin treatment influenced two gene modules linked to AD pathology: 1) a module related to proinflammation and transport/vesicle process that included a hub gene of Cd68, and 2) a module related to mitochondria function that included a hub gene of Atp5b. Amylin treatment restored the expression of most genes in the APP cortex toward levels observed in the WT cortex including 23 key hub genes in these two modules. In cultured activated microglia cell line BV-2, we validated that Cd68 expression was attenuated by amylin through binding to the amylin receptor. Using publically-available transcriptomic human data, we found that the expression levels of the orthologues of these hub genes, including Cd68 and Atp5b, strongly correlated with the neurofibrillary tangle burden in the AD brain and with Mini-Mental Status Exam scores. Our study is the first to show the transcriptome-wide targets of amylin treatment, and further supports the potential use of amylin-type peptides to treat AD.
2017-02-01 | GSE77373 | GEO
Project description:Accumulating evidences suggest that various epigenetic aberrations play definite roles in the pathogenesis of endometriosis. The aim of this study is to identify 1) the panel of aberrantly expressed genes that are epigenetically suppressed by histone acetylation in endometriosis; 2) the roles of CCAAT/enhancer-binding protein (C/EBP) alpha, one of the candidate molecules whose expression was epigenetically repressed in endometriotic cyst stromal cells (ECSCs), in the pathogenesis of endometriosis; and 3) the efficacy of the histone deacetylase inhibitors for the treatment of endometriosis.
2013-10-21 | GSE44207 | GEO
Project description:Smooth muscle cells (SMCs) and endothelial cells (ECs) constitute vasculature media and endothelium, respectively. Current treatments for cardiovascular disease inhibit SMC hyperplasia but also damage the protective endothelial lining, predisposing patients to thrombosis. Therapeutics targeting SMCs without collateral damage to ECs are highly desirable. However, differential (SMCs versus ECs) disease-associated regulations remain poorly defined. We conducted RNA-seq experiments to investigate SMC-versus-EC differential transcriptomic dynamics, following treatment of human primary SMCs and ECs with TNFα or IL-1β, both established inducers of SMC hyperplasia and EC dysfunction. To analyze combined SMC/EC transcriptomes we developed customized algorithms. Induced by TNFα or IL-1β, 212 and 263 genes respectively showed greater up-regulation in SMCs than in ECs (SMC-enriched), while 140 and 204 genes showed greater up-regulation in ECs over SMCs (EC-enriched). Analysis of gene interaction networks identified 5 common hubs and 4 common bottlenecks in the two SMC-enriched gene sets, and 8 hubs and 3 bottlenecks shared in the EC-enriched gene sets. Significantly, four gene modules were formed with these hubs and bottlenecks. While the JUN module (including JUN, KLF5, HIF1A, CXCL8, FOSL1) and FYN module (FYN, JAK2, MAP2, PIK3R3, DAB2, ASAP2) were SMC-enriched, the SMAD3 (SMAD3, CDKN1A, TRAF1, BCL6, CEBPD, TRIB3, ANK3) and XPO1 (XPO1, ETS2, SSH2, NDRG1, GFPT2?) modules were EC-enriched. As these core subnetworks respond to pathogenic stimulation in a SMC-versus-EC differential manner, they may inform potential intervention targets for selective mitigation of SMC hyperplasia without endothelial damage.
2018-02-14 | GSE96962 | GEO
Project description:micro RNA expression during adipogenesis of human mesenchynal stem cells. Cells transfected with wildtype human C/EBP-alpha (in expression vector pcDNA3.1) and overexpression of C/EBP-alpha for 48 hours were compared to control cells transfected with the empty vector.
2010-09-02 | E-MEXP-2085 | biostudies-arrayexpress