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GSE17172
Homo sapiens
18 Downloadable Samples
Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Human Burkitt's lymphoma ST486 cells were transduced with non-target control shRNA lentiviral vectors, FOXM1 shRNA, and MYB shRNA lentiviral vectors. Total RNA was isolated 24h later. cRNA was produced with the standard one-step IVT protocol (Affymetix) and hybridized in U95Av2 gene chips (Affymetrix).
Publication Title
Correlating measurements across samples improves accuracy of large-scale expression profile experiments.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
ChIP-on-chip has emerged as a powerful tool to dissect the complex network of regulatory interactions between transcription factors and their targets. However, most ChIP-on-chip analysis methods use conservative approaches aimed to minimize false-positive transcription factor targets. We present a model with improved sensitivity in detecting binding events from ChIP-on-chip data. Its application to human T-cells, followed by extensive biochemical validation, reveals that three transcription factor oncogenes, NOTCH1, MYC, and HES1, bind to several thousands target gene promoters, up to an order of magnitude increase over conventional analysis methods. Gene expression profiling upon NOTCH1 inhibition shows broad-scale functional regulation across the entire range of predicted target genes, establishing a closer link between occupancy and regulation. Finally, the increased sensitivity reveals a combinatorial regulatory program in which MYC co-binds to virtually all NOTCH1-bound promoters. Overall, these results suggest an unappreciated complexity of transcriptional regulatory networks and highlight the fundamental importance of genome-scale analysis to represent transcriptional programs.
Publication Title
ChIP-on-chip significance analysis reveals large-scale binding and regulation by human transcription factor oncogenes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Sequencing studies from several model systems have suggested that diverse and abundant small RNAs may derive from tRNA, but the function of these molecules remains undefined. Here we demonstrate that one such tRNA fragment, cloned from human B cells and designated CU1276, in fact possesses the functional characteristics of a microRNA, including a DICER1-dependent biogenesis, physical association with Argonaute proteins, and the ability to repress mRNA transcripts in a sequence-specific manner. The gene expression profiling undertaken for this study was done in order to assay mRNA-level changes in 293T cells upon modulation of CU1276 levels, and thereby to identify direct targets of this sequence. Ultimately, we fully validated the endogenous gene RPA1 as a CU1276 target.
Publication Title
tRNA-derived microRNA modulates proliferation and the DNA damage response and is down-regulated in B cell lymphoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Systemic hypertension increases cardiac workload and subsequently induces signaling networks in heart that underlie myocyte growth (hypertrophic response) through expansion of sarcomeres with the aim to increase contractility. However, conditions of increased workload can induce both adaptive and maladaptive growth of heart muscle. Previous studies implicate two members of the AP-1 transcription factor family, junD and fra-1, in regulation of heart growth during hypertrophic response. In this study, we investigate the function of the AP-1 transcription factors, c-jun and c-fos, in heart growth. Using pressure overload-induced cardiac hypertrophy in mice and targeted deletion of Jun or Fos in cardiomyocytes, we show that c-jun is required for adaptive cardiac hyphertrophy, while c-fos is dispensable in this context. c-jun promotes expression of sarcomere proteins and suppresses expression of extracellular matrix proteins. Capacity of cardiac muscle to contract depends on organization of principal thick and thin filaments, myosin and actin, within the sarcomere. In line with decreased expression of sarcomere-associated proteins, Jun-deficient cardiomyocytes present disarrangement of filaments in sarcomeres and actin cytoskeleton disorganization. Moreover, Jun-deficient hearts subjected to pressure overload display pronounced fibrosis and increased myocyte apoptosis finally resulting in dilated cardiomyopathy. In conclusion, c-jun but not c-fos is required to induce a transcriptional program aimed at adapting heart growth upon increased workload.
Publication Title
The AP-1 transcription factor c-Jun prevents stress-imposed maladaptive remodeling of the heart.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Analysis of gene expression at RNA level by 4 different cell sorted Vg9Vd2 subsets (Subset 1=CD28+CD27+, Subset2=CD28-CD27+, Subset 3=CD28-CD7-CD16-, Subset 4 = CD28-CD27-CD16+). Results highlight differences in RNA expression characterising these four cell populations into distinct phenotypic subsets with distinct functional potential
Publication Title
Heterogeneous yet stable Vδ2(+) T-cell profiles define distinct cytotoxic effector potentials in healthy human individuals.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The overarching goal of this study was to explore the antitumor activity of Z-endoxifen, a tamoxifen metabolite, with first-line endocrine therapies tamoxifen and letrozole in the letrozole-sensitive MCF7 aromatase expressing model (MCF7AC1), and with second-line endocrine therapies including tamoxifen, fulvestrant, exemestane, and exemestane plus everolimus, in letrozole-resistant MCF7 model (MCF7LR) in vivo.
Publication Title
Antitumor activity of Z-endoxifen in aromatase inhibitor-sensitive and aromatase inhibitor-resistant estrogen receptor-positive breast cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
A lactobacilli dominated microbiota in most pre and post-menopausal women is an indicator of vaginal health. A Nugent scoring system serves as a proxy for determining the ratio of lactobacilli to other vaginal inhabitants where a high score usually represents a diseased state, whilst an intermediate score represents a warning zone. The objective of this double blinded, placebo-controlled crossover study was to evaluate in 14 post-menopausal women with an intermediate score, the effect of vaginal administration of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 on the microbiota and host response. The probiotic treatment did not result in changes to clinical parameters such as dryness, irritation and comfort, compared to when placebo was applied. Analysis using 16S rRNA sequencing and metabolomics profiling revealed that the proportional abundance of Lactobacillus was increased following probiotic administration as compared to placebo, which was weakly associated with an increase in lactate levels. Analysis of host responses by microarray showed the probiotics had an immune-modulatory response and multiplex cytokine analysis showed up-regulation of IL-5. This is the first study to use an interactomic approach for the study of vaginal probiotic administration in post-menopausal women. It shows that in some cases multifaceted approaches are required to detect the subtle trigger molecular changes induced by the host to instillation of probiotic strains.
Publication Title
A systems biology approach investigating the effect of probiotics on the vaginal microbiome and host responses in a double blind, placebo-controlled clinical trial of post-menopausal women.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 222 Downloadable Samples
IlluminaHiSeq2000
Description
Dendritic cells (DCs) are antigen sensing and presenting cells that are essential for effective immunity. Existing as a multi-subset population, divided by distinct developmental and functional characteristics1,2, DC subsets play important and unique roles in responses to pathogens, vaccines and cancer therapies, as well as during immune-pathologies. Therefore therapeutic manipulation of the DC compartment is an attractive strategy. However, our incomplete knowledge of the inter-relationship between DC subsets and how they develop from progenitors in the bone marrow (BM) has so far limited the realization of their therapeutic potential. DCs arise from a cascade of progenitors that gradually differentiate in the BM; first, the macrophage DC progenitor (MDP), then common DC progenitor (CDP), and lastly the Pre-DC, which will leave the BM to seed peripheral tissues before differentiating into mature DCs3,4. While the basic outline of this process is known, how subset commitment and development is regulated at the molecular level remains poorly understood. Here we reveal that the Pre-DC population in mice is heterogeneous, containing uncommitted Ly6c+/-Siglec-H+ cells as well as Ly6c+Siglec-H- and Ly6c-Siglec-H- sub-populations that are developmentally fated to become Th2/17-inducing CD11b+ DCs and Th1-inducing CD8a+ DCs, respectively. Using single cell analysis by microfluidic RNA sequencing, we found that DC subset imprinting occurred at the mRNA level from the CDP stage, revealing that subset fate is defined in the BM and not in peripheral tissues. Single cell transcriptome analysis allowed identification of the molecular checkpoints between progenitor stages and revealed new regulators of DC-poiesis, shedding light on the role of cell cycle control and specific transcription factors in DC lineage development. These data advance our knowledge of the steady-state regulation of DC populations and open promising new avenues for investigation of the therapeutic potential of DC subset-specific targeting in vivo to improve vaccine-based and immunotherapeutic strategies. Overall design: Single cell mRNA sequencing was used to investigate the transcriptomic relationships within the Dendritic cell precursor compartment within the BM as well as between single Dendritic cell precursors
Publication Title
Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 57 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Calcineurin/NFAT/IL-2 signaling pathway is activated in dendritic cells (DC) upon encounter of glucan, the main component of the fungal cell wall, raising the question about the role of NFAT-regulated genes in DC biology in vivo. To directly assess the function of IL-2 secreted by DC, we analyzed mice lacking of IL-2 in the DC lineage, CD4-expressing cells and with complete deletion of IL-2 in the germ line in a mouse model of pulmonary fungal infection. Here we found that specifically the loss of IL-2 in DC resulted in increased mice mortality upon the fungus Aspergillus fumigatus challenge and expansion of Th17 cells in the lung. We demonstrated that only CD103+DC were able to release IL-2 in acute phase of pulmonary Aspergillosis through the Ca2+-Calcineurin-NFAT signaling. We also found that NFAT mediates IL-23 transcription in lung DC, where IL-2 results essential in restraining the priming of a pathogenic infiltrating IL-17+Sca1+CD90+CD4+ cell with stem cell like properties. Thus, IL-2 and IL-23 secreted by DC in the lung have an antagonistic relationship on the Th17 differentiation program with IL-2 inducing T cell differentiation and IL-23 inducing a stem cell like molecular signature to Th17 cells upon Aspergillus challenge. DC-Il2-/- then confer the Th17 stemness, releasing IL-23 in response to the fungus contributing to the development of a Th17 cell effector population, particularly pathogenic in infection.
Publication Title
CD103(+) Dendritic Cells Control Th17 Cell Function in the Lung.
Sample Metadata Fields
Cell line, Treatment
View Samples