Filters
Technology
Platform
GSE146093
Homo sapiens
64 Downloadable Samples
Affymetrix Clariom S Human array (clariomshuman), Infinium MethylationEPIC
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Epigenomics and transcriptomics of systemic sclerosis CD4+ T cells reveal long-range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci.
Sample Metadata Fields
Sex, Subject
View Samples- Homo sapiens
- 64 Downloadable Samples
Affymetrix Clariom S Human array (clariomshuman)
Description
Epigenomic and transcriptomic analysis of Systemic Sclerosis CD4+ T cells reveals long range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci range dysregulation of key inflammatory pathways mediated by disease-associated
Publication Title
Epigenomics and transcriptomics of systemic sclerosis CD4+ T cells reveal long-range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci.
Sample Metadata Fields
Sex, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
IlluminaGenomeAnalyzerIIx
Description
The c-MYC oncogene is a key transcription factor deregulated in most human tumors. Histone marks associated with transcriptionally active genes in euchromatic islands define the set of high-affinity c-MYC targets. The mechanisms involved in their recognition by c-MYC are not known but likely involve chromatin-remodelling and chromatin-modifying complexes. Here, we show that c-MYC interacts with BPTF, a core subunit of the NURF complex that binds active chromatin. BPTF is required for the activation of the full c-MYC transcriptional programme in fibroblasts. BPTF knockdown leads to a decrease in c-MYC recruitment to DNA and to changes in chromatin accessibility. Using BPTF-null MEFs we show that BPTF is necessary for c-MYC-driven proliferation, G1-S progression, and replication stress, but not for c-MYC-driven apoptosis. Consistently, BPTF is required for the proliferation of cells driven by c-MYC, such as Burkitt lymphoma, and its expression in human cancer lines correlates with the activation of c-MYC gene signatures. Our findings point to the c-MYC-BPTF axis as a potential therapeutic target in cancer. Overall design: To assess whether BPTF is required for the transcriptional activity of c-MYC, human foreskin fibroblasts (HFF) were stably transduced with the chimeric MYC-ER cDNA (HFF MYC-ER) and infected with lentiviruses coding for either control (shNt) or BPTF-targeting shRNAs. Cells were serum-starved for 2 days to achieve quiescence and then treated with 4-hydroxytamoxifen (4-OHT)
Publication Title
BPTF is required for c-MYC transcriptional activity and in vivo tumorigenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Aim: To determine the role of NOTCH during the response-to-injury and subsequent chronic inflammatory process of the arterial wall underlying atherosclerosis. Methods and results: We have generated an endothelial-specific RBPJK depleted mice using the Cdh5 cadherin promoter (ApoE-/-;RBPJflox/flox;Cdh5- CreERT). Endothelial-specific deletion of the Notch effector RBPJK or systemic deletion of the Notch1 receptor in athero-susceptible ApoE-/- mice fed a HC diet for 6 weeks resulted in reduced atherosclerosis in the aortic arch and sinus. Intravital microscopy revealed decreased leukocyte rolling on the endothelium of ApoE-/-;RBPJflox/flox;Cdh5- CreERT, that correlated with the lesser presence of leukocyts and macrophages in the vascular wall. Consistent with this, transcriptome analysis revealed that proinflammatory and endothelial activation pathways were downregulated in atherosclerotic tissue of RBPJk-mutant mice.. Jagged1 signaling upregulation in endothelial cells promotes the physical interaction and nuclear translocation of the intracellular domain of the Notch1 receptor (N1ICD) with NF-kB,. This N1ICD and NF-kB interaction is required for reciprocal transactivation of target genes including vascular cell adhesion molecule-1 (Vcam1). Conclusions: Notch signaling pathway inactivation decreases leukocyte rolling, thereby preventing endothelial dysfunction and vascular inflammation. Thus attenuating Notch signaling may constitute a useful therapeutic strategy for atherosclerosis. Key words: atherosclerosis, endothelium, signaling pathways, Notch, NF-kB, transcriptional regulation Overall design: RNA was isolated from the aortic arches of three ApoE-/-;RBPJflox/flox and three ApoE-/-; RBPJflox/flox;Cdh5-CreERTmice
Publication Title
Endothelial Jag1-RBPJ signalling promotes inflammatory leucocyte recruitment and atherosclerosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Effect of FGF2 on the transcriptional profile of microvascular endothelial cells
Publication Title
A pro-inflammatory signature mediates FGF2-induced angiogenesis.
Sample Metadata Fields
Specimen part, Cell line, Compound
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Elimination of peripheral retinal axons leads to changes in gene expression in both visual and somatosensory thalamic neurons.
Publication Title
Prenatal thalamic waves regulate cortical area size prior to sensory processing.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
We examined the effect of ablation of Tet2, an epigenetic regulator of gene transcription, in the global programme of gene expression at baseline, without pro-inflammatory activation, in macrophages.
Publication Title
Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
We examined the effect of ablation of Tet2, an epigenetic regulator of gene transcription, in the global programme of gene expression underlying pro-inflammatory activation of macrophage.
Publication Title
Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Hutchinson-Gilford Progeria Syndrome (HGPS) is caused by a point mutation in the LMNA gene that activates a cryptic donor splice site and yields a truncated form of prelamin A called progerin. Small amounts of progerin are also produced during normal aging. Studies with mouse models of HGPS have allowed the recent development of the first therapeutic approaches for this disease. However, none of these earlier works have addressed the aberrant and pathogenic LMNA splicing observed in HGPS patients because of the lack of an appropriate mouse model. We report herein a genetically modified mouse strain that carries the HGPS mutation. These mice accumulate progerin, present histological and transcriptional alterations characteristic of progeroid models, and phenocopy the main clinical manifestations of human HGPS, including shortened life span and bone and cardiovascular aberrations. By using this animal model, we have developed an antisense morpholinobased therapy that prevents the pathogenic Lmna splicing, dramatically reducing the accumulation of progerin and its associated nuclear defects. Treatment of mutant mice with these morpholinos led to a marked amelioration of their progeroid phenotype and substantially extended their life span, supporting the effectiveness of antisense oligonucleotidebased therapies for treating human diseases of accelerated aging.
Publication Title
Splicing-directed therapy in a new mouse model of human accelerated aging.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This experiment investigates differences in global gene expression between ACC and NSG.
Publication Title
Targeting the Oncogenic Transcriptional Regulator MYB in Adenoid Cystic Carcinoma by Inhibition of IGF1R/AKT Signaling.
Sample Metadata Fields
Specimen part
View Samples