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GSE56583
Homo sapiens
43 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
The objective of the overall study was to determine the effects of oral vitamin D supplementation on alveolar macrophages from human subjects. In this substudy, subjects treated with vitamin D (intervention group) in paired analysis had small, but significant effects on immune-related differential gene expression pre versus post supplementation.
Publication Title
Effects of vitamin D supplementation on alveolar macrophage gene expression: preliminary results of a randomized, controlled trial.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
CD90+ prostate cancer-associated (CP) stromal cells represent a disease cell type found only in tumor tissue. Genetic reprogramming by induced pluripotent stem (iPS) cell technology might be used to normal gene expression of diseased cells thereby providing a cure. The resultant iPS cells would no longer express the disease program, and, like stem cells, might respond to normal differentiative signaling. Thus, CP stromal cells, isolated from tumor tissue and cultured in vitro, were transfected with POU5F1/LIN28/NANOG/SOX2 lentiviral vectors. iPS cells were obtained at a frequency of 10^4. Transcriptome analysis showed an almost complete match in gene expression between the iPS cells and human embryonic stem cells. Genes of CP stromal cells were fully inactivated.
Publication Title
Reprogramming of prostate cancer-associated stromal cells to embryonic stem-like.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 4000
Description
Definitive hematopoietic cells arise from hemogenic endothelium during mid-gestation, indicating a direct link between blood and the endothelial-lined vessels. We sought to determine whether mutations initiated in the hemogenic endothelium would yield hematopoietic abnormalities or malignancies. Here we demonstrate that transposon mutagenesis targeting endothelial cells in mice promotes the development of hematopoietic pathologies that are both myeloid and lymphoid in nature. Sequencing of the disrupted genes identified several previously recognized candidate cancer drivers and furthermore revealed that mutations in the lipid kinase Pi4ka can result in myeloid and erythroid dysfunction. Subsequent validation experiments showed that targeted inactivation of the Pi4ka catalytic domain or reduction in mRNA expression inhibited myeloid and erythroid cell differentiation in vitro and promoted anemia in vivo through a mechanism that includes, but it is not limited to deregulation of Akt signaling. Finally, we provide evidence linking PI4KAP2, previously considered a “pseudogene”, with human myeloid and erythroid leukemia. Overall design: mRNA transcriptional comparison between two pieces of spleen from three SBxVEC-Cre+ animals and three control animals to assess clonality of each spleen as a whole.
Publication Title
A Forward Genetic Screen Targeting the Endothelium Reveals a Regulatory Role for the Lipid Kinase Pi4ka in Myelo- and Erythropoiesis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
We analyze the contribution of alternative splicing to the transcriptional complexity in adipose tissue and the development of diet-induced obesity. Overall design: We use Next generation sequencing analysis of eWAT from control and Nova1 and Nova2-deficient mice fed with a control diet
Publication Title
An alternative splicing program promotes adipose tissue thermogenesis.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- NextSeq 500
Description
To establish effective multitargeted KRAS pathway therapy, we analyzed mediators of acquired resistance to chronic momelotinib and MEK inhibitor exposure in A549 cells. Since inhibitor resistance was completely reversible after drug withdrawal for several passages, suggesting epigenetic reprogramming, we investigated whole mRNA expression profiles in A549, momelotinib and selumetinib resistant (MSR)-A549 cells and MSR-A549 cells following drug withdrawal for 10 days. In parallel, we also examined mRNA expression profiles of MSR-A549 cells treated with the BET inhibitor JQ1, to identify specific targets regulated by H3K27 acetylation. Overall design: mRNA profile of MSR-A549 cells with or without JQ1 treatment.
Publication Title
Overcoming Resistance to Dual Innate Immune and MEK Inhibition Downstream of KRAS.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 56 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Defective T Memory Cell Differentiation after Varicella Zoster Vaccination in Older Individuals.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 56 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
To identify host factors that influence the immunogenicity of the attenuated VZV pOka vaccine strain and the efficacy of VZV vaccination, we immunized 39 individuals aged 50 to 75 years, including 9 monozygotic twin pairs. We measured VZV-specific T cell frequencies by IFN-specific ELISpot, and VZV-specific antibody titers by ELISA. Whole gene expression arrays were performed on vaccinees before (n=28) and one (n=18) or three days (n=10) after vaccination. Cell-specific gene expression profiles were generated by deconvolution using previously described algorithms. Only very few neutrophil- and lymphocyte-related genes changed in expression from day 0 to 1. Significant changes for monocyte-related genes were found, but even here the number of probes with a significant change was low after adjusting for false discovery. When expression changes in monocyte-derived genes were analyzed for their correlation with T cell responses, we identified 493 probes corresponding to 479 genes that correlated with generation of VZV-specific effector T cells and 641 probes corresponding to 621 genes that correlated with the subsequent contraction phase with p<0.05. Interestingly, these two sets of genes were significantly overlapping, i.e., the same changes that were positively or negatively correlated with expansion inversely predicted contraction; their effects therefore cancelled out in determining net benefit in memory cell generation.
Publication Title
Defective T Memory Cell Differentiation after Varicella Zoster Vaccination in Older Individuals.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
CpG 1826 binds to Toll-like receptor (TLR)9, whereas influenza virus PR8 activates pDC via TLR7. Differential stimulation of pDCs is expected to result in unique activation mechanism(s) leading to a different phenotypically and functionally matured pDC
Publication Title
Two distinct activation states of plasmacytoid dendritic cells induced by influenza virus and CpG 1826 oligonucleotide.
Sample Metadata Fields
No sample metadata fields
View Samples- Gallus gallus
- 12 Downloadable Samples
- Affymetrix Chicken Gene 1.1 ST Array (chigene11st)
Description
White Striping and Wooden Breast (WS/WB) are abnormalities increasingly occurring in the fillets of high breast yield and growth rate chicken hybrids. These defects lead to consistent economic losses for poultry meat industry, as affected broilers fillets present an impaired visual appearance that negatively affects consumers acceptability. Previous studies have highlighted in affected fillets a deeply damaged muscle, showing profound inflammation, fibrosis and lipidosis. The present study investigated the differentially expressed genes and pathways linked to the compositional changes observed in WS/WB breast muscles, in order to outline a more complete framework of the gene networks related to the occurrence of this complex pathological picture. The biochemical composition was performed on 20 Pectoralis major samples obtained from high breast yield and growth rate broilers (10 affected vs. 10 normal) and 12 out of the 20 samples were used for the microarray gene expression profiling (6 affected vs. 6 normal). The obtained results indicate strong changes in muscle mineral composition, coupled to an increased deposition of fat. In addition, 204 differentially expressed genes (DEG) were found: 102 up-regulated and 102 down-regulated in affected breasts. The gene expression pathways found more altered in WS/WB muscles are those related to muscle development, polysaccharide metabolic processes, proteoglycans synthesis, inflammation and calcium signaling pathway. On the whole, the findings suggest that a multifactorial and complex etiology is associated with the occurrence of WS/WB muscle abnormalities, contributing to further define the transcription patterns associated to these myopathies.
Publication Title
Detection of differentially expressed genes in broiler pectoralis major muscle affected by White Striping - Wooden Breast myopathies.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 384 Downloadable Samples
- NextSeq 500
Description
Immune checkpoint blockade has shown tremendous anti-tumor potential in the clinic. However, these therapies are only effective in a subset of patients, so identification of additional immunomodulatory molecules that enhance the anti-tumor activity of these treatments may expand their clinical utility. In particular, identifying small molecules that complement existing immunotherapies has been relatively unexplored, so we performed a small molecule screen to identify compounds that can enhance co-inhibitory molecule blockade, to improve the anti-tumor adaptive immune response. Our unbiased screen identified inhibitors of cyclin-dependent kinase 4 and 6 (CDK4/6), including the FDA-approved palbociclib, as a class of small molecule compounds that exhibited significant immunostimulatory activity in vitro. In accordance with our in vitro finding of enhanced NFAT signaling, single-cell RNA-sequencing confirmed that in vivo exposure to CDK4/6 inhibitors enhanced NFAT signaling in tumor infiltrating T cells. Moreover, our results revealed that CDK4/6 inhibition up-regulated activation molecules and down-regulated suppressive molecules in these cells. CDK4/6 inhibition also increased the number of T cells with activated TCR (T cell receptor) signaling, as well as factors that are important for signal transduction downstream of TCR signaling. In summary, the impact of CDK4/6i on cell cycle progression and T cell proliferation are balanced favorably towards increased T cell recruitment and enhanced effector cell function, mediated in part by activation of the NFAT family of transcription factors. Further, our results demonstrate that CDK4/6i enhances PD-1 blockade through increased T-cell effector function and inhibition of immune suppressive cytokine production. While prolonged CDK4/6i treatment could be immunosuppressive due to adverse effects on lymphocyte proliferation, properly timed/sequenced CDK4/6i may potentiate the clinical impact of anti-PD-1/PD-L1 antibodies. As palbociclib is FDA-approved and multiple other CDK4/6 inhibitors are in clinical trials, we expect that this hypothesis will undergo rapid testing in humans. Overall design: Single-cell comparison of control and CDK4/6 inhibitor treated tumor infiltrating T cells
Publication Title
CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples