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GSE3995
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- Homo sapiens
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
Dysregulated inflammation is implicated in the pathobiology of aging, yet platelet-leukocyte interactions and downstream inflammatory gene synthesis in older adults remains poorly understood. Highly-purified human platelets and monocytes were isolated from healthy younger (age<45, n=37) and older (age60, n=30) adults and incubated together under autologous and non-autologous conditions. Inflammatory gene synthesis by monocytes, basally and in the presence of platelets, was examined. Next-generation RNA-sequencing allowed for unbiased profiling of the platelet transcriptome in aging. Basal IL-8 and MCP-1 synthesis by monocytes alone did not differ between older and younger adults. However, in the presence of autologous platelets, monocytes from older adults synthesized greater IL-8 (415 vs. 92 ng/mL, p<0.0001) and MCP-1 (867150 vs. 21636 ng/mL, p<0.0001) than younger adults. Non-autologous experiments demonstrated that platelets from older adults were sufficient for upregulating inflammatory gene synthesis by monocytes. Using RNA-seq followed by validation via RT-PCR and immunoblot, we discovered that granzyme A (GrmA), a serine protease not previously identified in human platelets, is increased in aging (~9-fold vs. younger adults, p<0.05) and governs increased IL-8 and MCP-1 synthesis through TLR4 and caspase-1. Inhibiting GrmA reduced the excessive IL-8 and MCP-1 synthesis in older adults to levels similar to younger adults. In summary, human aging is associated with changes in the platelet transcriptome and proteome. GrmA is present and bioactive in human platelets, is higher in older adults, and controls inflammatory gene synthesis by monocytes. Alterations in the platelet molecular signature and downstream signaling to monocytes may contribute to dysregulated inflammatory syndromes and adverse outcomes in older adults.
Publication Title
Granzyme A in Human Platelets Regulates the Synthesis of Proinflammatory Cytokines by Monocytes in Aging.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The emergence of immune resistance variants during immunotherapy is poorly understood. We generated a highly immune resistant cell line (P3) from a susceptible cell line (P0) by subjecting it to 3 rounds of in vivo immune selection. Subsequently, microarray analysis of P0 and P3 was performed to identify genes that may contribute to the increase in immune resistance.
Publication Title
Ectopic expression of vascular cell adhesion molecule-1 as a new mechanism for tumor immune evasion.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- IlluminaHiSeq2000
Description
Background: Kawasaki Disease (KD) is a childhood illness of suspected infectious etiology that causes medium-sized muscular arteritis, most critically affecting the coronary arteries. No single diagnostic test exists, hampering early diagnosis and treatment. Approximately 25% of untreated patients develop coronary artery disease, and children who are treated with intravenous gammaglobulin but do not respond are also at high risk. Subacute/chronic arteritis and luminal myofibroblastic proliferation are the pathologic processes occurring in KD CA after the second week of illness, when neutrophilic necrotizing arteritis has subsided. The specific dysregulated immune pathways contributing to subacute/chronic arteritis have been unknown, hampering the development of effective immunomodulatory therapies for patients not responding to intravenous gammaglobulin therapy. Methods and Results: Deep RNA sequencing was performed on KD (n=8) and childhood control (n=7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Molecular pathways involving T helper cell, cytotoxic T lymphocyte, dendritic cells, and antigen presentation were the most significantly dysregulated. There was significant upregulation of immunoglobulin and type I interferon-stimulated genes. 80 upregulated extracellular genes encoding secreted proteins are candidate biomarkers of KD arteritis. Conclusions: The immune transcriptional profile in KD coronary artery tissues is primarily T helper and cytotoxic lymphocyte-mediated, and has features of an antiviral immune response such as type I interferon-stimulated gene expression. This first report of the KD coronary artery transcriptome identifies specific dysregulated immune response pathways that can inform the development of new therapies for and biomarkers of KD arteritis, and provide direction for future etiologic studies. Overall design: Primary analysis: 8 KD coronary arteries versus 7 childhood control coronary arteries. Subanalysis 1: 4 untreated KD coronary arteries versus 7 childhood control coronary arteries and subanalysis 2: 4 treated KD coronary arteries versus 7 childhood control coronary arteries
Publication Title
The transcriptional profile of coronary arteritis in Kawasaki disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- NextSeq 500
Description
Based on RNA-seq, we performed transcriptomic profiling to examine the differences between Orthotopic and IVBL (in vivo bone lesion). We found Calcium signalling is upregulated in IVBL and correlated to the expression of gap junctions. Overall design: Orthotopic tumors and Bone lesions, all developed by MCF-7, are subject to NGS and then analyzed.
Publication Title
The Osteogenic Niche Is a Calcium Reservoir of Bone Micrometastases and Confers Unexpected Therapeutic Vulnerability.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- NextSeq 500
Description
Based on next generation RNA-seq, we examed Arsenic trioxide treatment (ATO) effect on MSCs-interacting MCF7 cells in 3D cultures. We found gap junction protein Cx43 is dramatically downregulated after ATO treatment.. Overall design: human breast cancer cell line MCF-7 cells cocultured with mouse MSCs in 3D culture, with or without ATO treatment, are subject to NGS and then analyzed.
Publication Title
The Osteogenic Niche Is a Calcium Reservoir of Bone Micrometastases and Confers Unexpected Therapeutic Vulnerability.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 92 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Up-regulation of a HOXA-PBX3 homeobox-gene signature following down-regulation of miR-181 is associated with adverse prognosis in patients with cytogenetically abnormal AML.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 92 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Increased expression levels of miR-181 family members have been shown to be associated with favorable outcome in patients with cytogenetically normal acute myeloid leukemia. Here we show that increased expression of miR-181a and miR-181b is also significantly (P < .05; Cox regression) associated with favorable overall survival in cytogenetically abnormal AML (CA-AML) patients. We further show that up-regulation of a gene signature composed of 4 potential miR-181 targets (including HOXA7, HOXA9, HOXA11, and PBX3), associated with down-regulation of miR-181 family members, is an independent predictor of adverse overall survival on multivariable testing in analysis of 183 CA-AML patients. The independent prognostic impact of this 4-homeobox-gene signature was confirmed in a validation set of 271 CA-AML patients. Furthermore, our in vitro and in vivo studies indicated that ectopic expression of miR-181b significantly promoted apoptosis and inhibited viability/proliferation of leukemic cells and delayed leukemogenesis; such effects could be reversed by forced expression of PBX3. Thus, the up-regulation of the 4 homeobox genes resulting from the down-regulation of miR-181 family members probably contribute to the poor prognosis of patients with nonfavorable CA-AML. Restoring expression of miR-181b and/or targeting the HOXA/PBX3 pathways may provide new strategies to improve survival substantially.
Publication Title
Up-regulation of a HOXA-PBX3 homeobox-gene signature following down-regulation of miR-181 is associated with adverse prognosis in patients with cytogenetically abnormal AML.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
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