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SRP192094
Homo sapiens
12 Downloadable Samples
Illumina HiSeq 4000
Description
We generated a human EFTUD2 knockdown cell line using a CRISPR cas9 nickase strategy to investigate the effects of decreased expression of core spliceosome components on cell characteristics and global transcriptome expression/splicing patterns Overall design: 6 biological replicates of WT or CRISPR knock-down cells were generated and analysed by RNA-Seq
Publication Title
Disease modeling of core pre-mRNA splicing factor haploinsufficiency.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Ascending aortic aneurysms (AscAA) are a life-threatening disease whose molecular basis is poorly understood. Mutations in NOTCH1 have been linked to bicuspid aortic valve (BAV), which is associated with AscAA. Here, we describe a novel role for Notch1 in AscAA. We found that Notch1 haploinsufficiency exacerbated the aneurysmal aortic root dilation seen in the Marfan syndrome mouse model and that heterozygous deletion of Notch1 in the second heart field (SHF) lineage recapitulated this exacerbated phenotype. Lineage tracing analysis showed that loss of Notch1 in the SHF reduces the number of SHF-derived smooth muscle cells in the aortic root, and RNA-seq analysis demonstrated distinct in vivo expression patterns between lineage-specific regions of the ascending aorta. Finally, Notch1+/- mice in a predominantly 129S6 background develop aortic root dilation, indicating that loss of Notch1 independently predisposes to AscAA. These findings are the first to demonstrate a SHF lineage-specific role for Notch1 in AscAA and suggest that genes linked to the development of BAV may also contribute to the associated aortopathy. Overall design: To determine why dilation was localized to the aortic root in Notch1.129S6+/- mice, RNA-sequencing was performed on proximal and distal ascending aortic tissue from Notch1.129S6+/- mice and wildtype littermates at 2 months of age. Transcriptome analysis was utilized to better understand why the dilation was localized to the aortic root. Hierarchical cluster analysis grouped these samples based on location first and then genotype, and showed that cells of the proximal and distal ascending aorta have distinct gene expression patterns in vivo.
Publication Title
Notch1 haploinsufficiency causes ascending aortic aneurysms in mice.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 37 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Multi-omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in Type 2 diabetic obesity.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Analysis of skeletal muscle gene expression from type 2 diabetic volunteers before and after 16 weeks of chronic exercise training (two groups, one undergoing aerobic ecercise and the other resistance training exercise)
Publication Title
Multi-omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in Type 2 diabetic obesity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 348 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We aimed to identify the gene network and pathway biology associated with response to vaccine administration by determining genome-wide alterations in host RNA in children
Publication Title
Sex-Differential Non-Vaccine-Specific Immunological Effects of Diphtheria-Tetanus-Pertussis and Measles Vaccination.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Four Wnt-dependent and four Wnt-independent GSC cultures were grown in stem cell media and RNA expression between the two subsets evaluated Overall design: Four biological replicates each of Wnt-dependent and Wnt-independent GSC cultures
Publication Title
Wnt and Notch signaling govern self-renewal and differentiation in a subset of human glioblastoma stem cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
The spatial organization of chromosomes influences many nuclear processes including gene expression. The cohesin complex shapes the 3D genome by looping together CTCF sites along chromosomes. We show here that chromatin loop size can be increased, and that the duration with which cohesin embraces DNA determines the degree to which loops are enlarged. Cohesin's DNA release factor WAPL restricts the degree of this loop extension and also prevents looping between incorrectly oriented CTCF sites. We reveal that the SCC2/SCC4 complex promotes the extension of chromatin loops and the formation of topologically associated domains (TADs). Our data support the model that cohesin structures chromosomes through the processive enlargement of loops and that TADs reflect polyclonal collections of loops in the making. Finally, we find that whereas cohesin promotes chromosomal looping, it rather limits nuclear compartmentalization. We conclude that the balanced activity of SCC2/SCC4 and WAPL enables cohesin to correctly structure chromosomes. Overall design: RNAseq was performed in control, ?WAPL 3.3, ?WAPL 1.14, ?SCC4 and ?WAPL/?SCC4 cells in triplicate.
Publication Title
The Cohesin Release Factor WAPL Restricts Chromatin Loop Extension.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Glioblastomas grow in a rich neurochemical mileu, but targeting neurochemical signaling as a potential therapeutic avenue for these incurable tumors has been underexplored. Thus, we probed patient derived glioblastoma stem cells with a focused library of neurochemicals, to identify new therapeutic targets. Dopaminergic, serotonergic and cholinergic pathways were found to be active against glioblastoma. In particular, dopamine receptor D4 (DRD4) antagonists selectively inhibited glioblastoma growth in vitro and in vivo, in addition to showing synergistic effect with temozolomide. Small molecule or genetic antagonism of DRD4 suppressed ERK1/2 signaling and impaired autophagic flux causing accumulation of autophagic vacuoles and ubiquitinated proteins, associated with G0/G1 cell cycle arrest. These data suggest a new mechanism for treating glioblastoma through modulating dopamine DRD4 signaling.
Publication Title
Inhibition of Dopamine Receptor D4 Impedes Autophagic Flux, Proliferation, and Survival of Glioblastoma Stem Cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Our objective was to determine the nature and extent of androgen regulation of gene expression in the female lacrimal, meibomian,and submandibular glands, and to explore the degree to which this control is the same as in male glands.
Publication Title
Influence of testosterone on gene expression in the ovariectomized mouse submandibular gland.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In autoimmune diseases, accumulation of activated leukocytes correlates with inflammation and disease progression, and therefore, disruption of leukocyte trafficking is an active area of research. The protein kinase Tpl2 (MAP3K8) regulates leukocyte inflammatory responses and is also being investigated for therapeutic inhibition during autoimmunity. Herein, we addressed the contribution of Tpl2 to the regulation of macrophage chemokine and chemokine receptor expression and subsequent migration in vivo using a mouse model of Tpl2 ablation. We found that gene expression of the chemokine ligands CCL2, CCL7, CXCL2, and CXCL3 as well as the chemokine receptors CCR1 and CCR5 were reduced in macrophages from the bone marrow and peritoneal cavities of tpl2-/- mice following stimulation with LPS. LPS stimulation repressed chemokine receptor expression of CCR1, CCR2 and CCR5. Notably, LPS-induced repression of CCR1 and CCR5 was significantly enhanced in Tpl2-deficient macrophages and was observed to be dependent upon Erk activation and independent of PI3K and mTOR signaling. Consistent with alterations in chemokine and chemokine receptor expression, tpl2-/- macrophages were defective in trafficking to the peritoneal cavity following thioglycollate-induced inflammation. Overall, this study demonstrates a Tpl2-dependent mechanism for macrophage expression of both chemokine receptors and their ligands and provides further insight into how Tpl2 inhibition may disrupt inflammatory networks in vivo.
Publication Title
Tumor progression locus 2 (Tpl2) kinase promotes chemokine receptor expression and macrophage migration during acute inflammation.
Sample Metadata Fields
Treatment
View Samples