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GSE140145
Homo sapiens
12 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Anaplastic lymphoma kinase (ALK) is expressed in around 60% of glioblastomas and conveys tumorigenic function. Therefore, ALK inhibitory strategies with alectinib were investigated in glioblastoma cells. We demonstrated that alectinib inhibited proliferation and clonogenicity of ALK expressing glioblastoma initiating cells, whereas cells without ALK expression or after ALK depletion via knockdown showed primary resistance against alectinib. The aim of this analysis was to investigate molecular mechanisms of alectinib mediated treatment effects in the ALK expressing S24 cells, which represent a primary glioblastoma cell culture, and after knockdown of ALK.
Publication Title
cMyc and ERK activity are associated with resistance to ALK inhibitory treatment in glioblastoma.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The alarmins myeloid-related protein (MRP) 8 and MRP14 are the dominant cytoplasmic proteins in phagocytes. After release by activated phagocytes extracellular MRP8/MRP14 complexes promote inflammation in many diseases, including infections, allergies, autoimmune diseases, rheumatoid arthritis or inflammatory bowel disease. As receptors for the pro-inflammatory effects of human MRP8, the active component of the MRP8/MRP14-complex, Toll-like receptor (TLR) 4 and the multi-ligand receptor of advanced glycation end products (RAGE) are controversial discussed. Using a comparative bioinformatics analysis between genome-wide response patterns of monocytes to MRP8, endotoxin and different cytokines we demonstrated a dominant role of TLR4 during MRP8-mediated phagocyte activation. The relevance of this signaling pathway could be confirmed in independent cell models for TLR4 and RAGE dependent signaling in mouse and man. In addition to well-known proinflammatory functions of MRP8 our systems biology approach unraveled a novel anti-apoptotic effect of MRP8 on monocytes which was confirmed in independent functional experiments. Our data define the dominance of the TLR4-MRP8 axis in activation of human phagocytes which represents a novel attractive target for modulation of overwhelming innate immune responses.
Publication Title
Transcriptome assessment reveals a dominant role for TLR4 in the activation of human monocytes by the alarmin MRP8.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 186 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptome-based network analysis reveals a spectrum model of human macrophage activation.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 186 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Macrophage activation is associated with profound transcriptional reprogramming. Although much progress has been made in the understanding of macrophage activation, polarization and function, the transcriptional programs regulating these processes remain poorly characterized. We stimulated human macrophages with diverse activation signals, acquiring a dataset of 299 macrophage transcriptomes. Analysis of this dataset revealed a spectrum of macrophage activation states extending the current M1 versus M2-polarization model. Network analyses identified central transcriptional regulators associated with all macrophage activation complemented by regulators related to stimulus-specific programs. Applying these transcriptional programs to human alveolar macrophages from smokers and patients with chronic obstructive pulmonary disease (COPD) revealed an unexpected loss of inflammatory signatures in COPD patients. Finally, by integrating murine data from the ImmGen project we propose a refined, activation-independent core signature for human and murine macrophages. This resource serves as a framework for future research into regulation of macrophage activation in health and disease.
Publication Title
Transcriptome-based network analysis reveals a spectrum model of human macrophage activation.
Sample Metadata Fields
Subject, Time
View Samples- Homo sapiens
- 20 Downloadable Samples
Illumina HiScanSQ
Description
Macrophage activation is associated with profound transcriptional reprogramming. Although much progress has been made in the understanding of macrophage activation, polarization and function, the transcriptional programs regulating these processes remain poorly characterized. We stimulated human macrophages with diverse activation signals, acquiring a dataset of 299 macrophage transcriptomes. Analysis of this dataset revealed a spectrum of macrophage activation states extending the current M1 versus M2-polarization model. Network analyses identified central transcriptional regulators associated with all macrophage activation complemented by regulators related to stimulus-specific programs. Applying these transcriptional programs to human alveolar macrophages from smokers and patients with chronic obstructive pulmonary disease (COPD) revealed an unexpected loss of inflammatory signatures in COPD patients. Finally, by integrating murine data from the ImmGen project we propose a refined, activation-independent core signature for human and murine macrophages. This resource serves as a framework for future research into regulation of macrophage activation in health and disease. Overall design: Since transcriptional programs are further modulated on several levels including miRNAs we assessed the global spectrum of miRNA expression by miRNA-Seq in macrophages stimulated with IFN?, IL4 or with the combination of TNFa, PGE2 and P3C
Publication Title
Transcriptome-based network analysis reveals a spectrum model of human macrophage activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
siRNA-mediated inhibition compared to untreated cells and cells transfected with nonsense siRNA.
Publication Title
Yes-associated protein up-regulates Jagged-1 and activates the Notch pathway in human hepatocellular carcinoma.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Background: Ion channels are key determinants for the function of excitable cells but little is known about their role and involvement during cardiac development. Earlier work identified Ca2+-activated potassium channels of small and intermediate conductance (SKCas) as important regulators of neural stem cell fate. Here, we have investigated their impact on the differentiation of pluripotent cells towards the cardiac lineage. Methods and Results: We have applied the SKCa-activator EBIO on embryonic stem cells and identified this particular ion channel family as a new critical target involved in the generation of cardiac pacemaker-like cells: SKCa-activation led to rapid remodeling of the actin cytoskeleton, inhibition of proliferation, induction of differentiation and diminished teratoma formation. Time-restricted SKCa-activation induced cardiac mesoderm and commitment to the cardiac lineage as shown by gene regulation, protein and functional electrophysiological studies. In addition, the differentiation into cardiomyocytes was modulated in a qualitative fashion, resulting in a strong enrichment of pacemaker-like cells. This was accompanied by induction of the sino-atrial gene program and in parallel by a loss of the chamber-specific myocardium. In addition, SKCa activity induced activation of the Ras-Mek-Erk signaling cascade, a signaling pathway involved in the EBIO-induced effects.
Publication Title
Modulation of calcium-activated potassium channels induces cardiogenesis of pluripotent stem cells and enrichment of pacemaker-like cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 1500
Description
Here we investigated whether sterile triggers of inflammation induce trained immunity and thereby influence innate immune responses. Western diet (WD) feeding of Ldlr-/- mice induced systemic inflammation, which was undectable in serum soon after mice were shifted back to chow diet (CD). In contrast, myeloid cell responses towards innate stimuli remained broadly augmented. WD induced transcriptomic and epigenomic reprogramming of myeloid progenitor cells, leading to increased proliferation as well as enhanced innate immune and interferon responses towards in vivo LPS challenge. QTL analysis in human monocytes trained with oxidized low-density lipoprotein (oxLDL) and stimulated with LPS suggested inflammasome-mediated trained immunity. Consistently, Nlrp3-/-/Ldlr-/--deficient mice lacked WD-induced systemic inflammation or myeloid progenitor proliferation and reprogramming. Hence, NLRP3 mediates trained immunity following WD and could thereby arbitrate the potentially deleterious effects of trained immunity in inflammatory diseases. Overall design: Examination of GMPs in six different conditions by RNA-seq
Publication Title
Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 19 Downloadable Samples
- Illumina HiSeq 1500
Description
Here we investigated whether sterile triggers of inflammation induce trained immunity and thereby influence innate immune responses. Western diet (WD) feeding of Ldlr-/- mice induced systemic inflammation, which was undectable in serum soon after mice were shifted back to chow diet (CD). In contrast, myeloid cell responses towards innate stimuli remained broadly augmented. WD induced transcriptomic and epigenomic reprogramming of myeloid progenitor cells, leading to increased proliferation as well as enhanced innate immune and interferon responses towards in vivo LPS challenge. QTL analysis in human monocytes trained with oxidized low-density lipoprotein (oxLDL) and stimulated with LPS suggested inflammasome-mediated trained immunity. Consistently, Nlrp3-/-/Ldlr-/--deficient mice lacked WD-induced systemic inflammation or myeloid progenitor proliferation and reprogramming. Hence, NLRP3 mediates trained immunity following WD and could thereby arbitrate the potentially deleterious effects of trained immunity in inflammatory diseases. Overall design: Examination of GMPs in six different conditions by RNA-seq
Publication Title
Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming.
Sample Metadata Fields
Specimen part, Subject
View Samples- Macaca mulatta
- 8 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
In vitro oocyte maturation (IVM) holds great promise as a tool for enhancing clinical treatment of infertility, enhancing availability of non human primates for development of disease models, and facilitating endangered species preservation. However, IVM outcomes have remained significantly below success rates obtained using in vivo matured (VVM) oocytes from humans and non human primates. A cDNA array based analysis is presented, comparing the transcriptomes of VVM oocytes with IVM oocytes. We observe a small set of just 59 mRNAs that are differentially expressed between the two cell types. These mRNAs are related to cellular homeostasis, cell-cell interactions including growth factor and hormone stimulation and cell adhesion, and other functions such as mRNA stability and translation. Additionally, we observe in IVM oocytes overexpression of PLAGL1 and MEST, two maternally imprinted genes, indicating a possible interruption or loss of correct epigenetic programming. These results indicate that, under certain IVM conditions, oocytes that are molecularly highly similar to VVM oocytes can be obtained, however the interruption of normal oocyte-somatic cell interactions during the final hours of oocyte maturation may preclude the establishment of full developmental competence.
Publication Title
Effects of in vitro maturation on gene expression in rhesus monkey oocytes.
Sample Metadata Fields
No sample metadata fields
View Samples