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GSE50851
Mus musculus
39 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
ABSTRACT: The human growth hormone (hGH) minigene is frequently used in the derivation of transgenic mouse lines to enhance transgene expression. Although this minigene is present in the transgenes as a secondcistron, and thus not thought to be expressed, we found that three commonly used lines, Pdx1-CreLate, RIP-Cre, and MIP-GFP, each expressed significant amounts of hGH in pancreatic islets. Locally secreted hGH binds to prolactin receptors on cells, activates STAT5 signaling, and induces pregnancy-like changes in gene expression, thereby augmenting pancreatic cell mass and insulin content. In addition, islets of Pdx1-CreLate mice have lower GLUT2 expression and reduced glucose-induced insulin release and are protected against the cell toxin streptozotocin. These findings may be important when interpreting results obtained when these and other hGH minigene-containing transgenic mice are used.
Publication Title
Impaired islet function in commonly used transgenic mouse lines due to human growth hormone minigene expression.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 43 Downloadable Samples
NextSeq 500
Description
Metformin, the most widely administered diabetes drug, has been proposed as a candidate for host directed therapy for tuberculosis although very little is known about its effects on human host responses to Mycobacterium tuberculosis. When added in vitro to PBMCs isolated from healthy non-diabetic volunteers, metformin increased glycolysis, inhibited the mTOR targets, strongly reduced M. tuberculosis induced production of TNF-alpha (-58%), IFN-gamma (-47%) and IL-beta (-20%), while increasing phagocytosis. In healthy subjects, in vivo metformin intake induced significant transcriptional changes in whole blood and isolated PBMCs, with substantial down-regulation of genes related to inflammation and the type 1 interferon response. Metformin intake also increased monocyte phagocytosis (by 1.5 to 2 fold) and ROS production (+20%). These results show that metformin in humans has a range of potentially beneficial effects on cellular metabolism, immune function and gene-transcriptional level, that affect innate host responses to M. tuberculosis. This underlines the importance of cellular metabolism for host immunity and supports a role for metformin as host-directed therapy for tuberculosis. Overall design: Peripheral Mononuclear Cells taken from 11 healthy donors, prior to administration of metformin and after 5 days of metformin. Samples were stimulated with Mycobacterium tuberculosis lysate or cultured unstimulated for 4 hours. Total 88 samples, with 11 clinical replicates.
Publication Title
Metformin Alters Human Host Responses to Mycobacterium tuberculosis in Healthy Subjects.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
- NextSeq 500
Description
Metformin, the most widely administered diabetes drug, has been proposed as a candidate for host directed therapy for tuberculosis although very little is known about its effects on human host responses to Mycobacterium tuberculosis. When added in vitro to PBMCs isolated from healthy non-diabetic volunteers, metformin increased glycolysis, inhibited the mTOR targets, strongly reduced M. tuberculosis induced production of TNF-a (-58%), IFN-gamma (-47%) and IL-1ß (-20%), while increasing phagocytosis. In healthy subjects, in vivo metformin intake induced significant transcriptional changes in whole blood and isolated PBMCs, with substantial down-regulation of genes related to inflammation and the type 1 interferon response. Metformin intake also increased monocyte phagocytosis (by 1.5 to 2 fold) and ROS production (+20%). These results show that metformin in humans has a range of potentially beneficial effects on cellular metabolism, immune function and gene-transcriptional level, that affect innate host responses to M. tuberculosis. This underlines the importance of cellular metabolism for host immunity and supports a role for metformin as host-directed therapy for tuberculosis. Overall design: Ex vivo blood RNA samples analyzed from 11 healthy donors, prior to administration of metformin (control) and after 5 days of metformin (test). Total 22 samples, with 11 clinical replicates.
Publication Title
Metformin Alters Human Host Responses to Mycobacterium tuberculosis in Healthy Subjects.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
YAP is an oncogene and an inducer of Epithelial-to-Mesenchymal Transition (EMT).
Publication Title
Negative regulation of YAP by LATS1 underscores evolutionary conservation of the Drosophila Hippo pathway.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Establishment of a transcriptomic profile of human cells treated with genistein with particular emphasis on the assessment of the role of this isoflavone in regulation of expression of psoriasis-related genes stands for the present study. The hypothesis tested was that genistein modulates activity of psoriasis-related genes, by reducing the expression efficiency of genes revealing enhanced activity in psoriatic cells, and by stimulating the expression efficiency of genes revealing decreased activity in psoriatic cells. Results provide important information concerning the extent of action of genistein at the molecular level in terms of modulation of gene expression by this substance.
Publication Title
Molecular action of isoflavone genistein in the human epithelial cell line HaCaT.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 48 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Establishment of a transcriptomic profile of human cells treated with kaemferol, daidzein, kaemferol/genistein, or daidzein/genistein with particular emphasis on signature of genes coding for enzymes involved in glycosaminoglycan synthesis stands for the present study. The hypothesis tested was that kaemferol, daidzein, kaemferol/genistein, and daidzein/genistein influence expression of some genes, among which are those coding for enzymes required for the synthesis of different GAGs being pathologically accumulated in mucopolysaccharidoses. Results provide important information concerning the extent of action of kaemferol, daidzein, kaemferol/genistein, and daidzein/genistein at the molecular level in terms of modulation of gene expression.
Publication Title
Modulation of expression of genes involved in glycosaminoglycan metabolism and lysosome biogenesis by flavonoids.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Oxidative stress is a hallmark of inflammation in infection or sterile tissue injury. We show that partially oxidized phospholipids of microvesicles (MVs) from plasma of patients with rheumatoid arthritis or cells exposed to oxidative stress induce activation of TLR4. MVs from healthy donors or reconstituted synthetic MVs can be converted to TLR4 agonists by limited oxidation, while prolonged oxidation abrogates the activity. Activation by MVs mimics the mechanism of TLR4 activation by LPS. However, LPS and MVs induce significantly different transcriptional response profile in mouse BMDMs with a strong inflammation-resolving component induced by the endogenous signals. MVs thus represent a ubiquitous endogenous danger signal released under the oxidative stress, which underlies the pervasive role of TLR4 signaling in inflammation.
Publication Title
Toll-like receptor 4 senses oxidative stress mediated by the oxidation of phospholipids in extracellular vesicles.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
The biological features of ovarian cancer stem cells (OCSC) remain elusive, mainly because 1) most studies so far have focused on cell lines that recapitulate the human disease only to a limited extend; and 2) because the identification of OCSC has relied on markers inferred from different and unrelated tumor types. Our study has harnessed the intrinsic, stemness-related properties of OCSC to identify and isolate this cell subpopulation from primary cultures freshly established from high-grade serous ovarian cancer (HGSOC), the most common and aggressive from of the disease. In addition, OCSC were compared to stem cell-enriched cultures from fallopian tube epithelium, which is the most accredited tissue of origin for HGSOC. The transcriptomes of the two cell types were compared to infer genes differentially regulated in OCSC.
Publication Title
CD73 Regulates Stemness and Epithelial-Mesenchymal Transition in Ovarian Cancer-Initiating Cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Complex three-dimensional (3D) in vitro model systems that recapitulate human tumor biology are essential to better understand the pathophysiology of the disease and to aid in the discovery of novel anti-cancer therapies. 3D organotypic cultures exhibit intercellula communication, nutrient and oxygen gradients, and cell polarity that is lacking in traditional two-dimensional (2D) monolayer cultures. In the present study, we could demonstrate that 2D and 3D cancer models exhibit different drug sensitivities towards both targeted inhibitors of EGFR signaling and broad acting cytotoxic agents. Changes in the kinase activities of Erb family members and differential expression of apoptosis- and survival-associated genes before and after drug treatment may account for the differential drug sensitivities. Importantly, EGFR oncoprotein addiction was evident only in the 3D cultures mirroring the effect of EGFR inhibition in the clinic. Furthermore, targeted drug efficacy was strongly increased when incorporating cancer-associated fibroblasts into the 3D cultures. Taken together, we could provide conclusive evidence that complex 3D cultures are more predictive of the clinical outcome than their 2D counterparts. In the future, 3D cultures will be instrumental for understanding the mode of action of drugs, identifying genotype-drug response relationships and developing patient-specific and personalized cancer treatments.
Publication Title
Organotypic three-dimensional cancer cell cultures mirror drug responses <i>in vivo</i>: lessons learned from the inhibition of EGFR signaling.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Hypoxia triggers aggressive cancer growth and contributes to chemotherapy resistance. Novel therapeutic strategies aim at targeting hypoxia activated signaling pathways. Tumor hypoxia not only affects neoplastic tumor cells but also the surrounding stroma cells. Therefore, a novel ex vivo model was established, which allows the study of hypoxia effects in fragments of non-small cell lung cancer (NSCLC) with preserved tumor microenvironment and 3D-structure. Microarray analysis identified 107 significantly regulated genes with at least two-fold expression change in hypoxic compared to normoxic fragments. However, only four genes were significantly regulated in both subtypes, adenocarcinoma and squamous cell carcinoma. The hypoxic regulation of these four genes was verified in an independent set using quantitative PCR.
Publication Title
Hypoxia increases membrane metallo-endopeptidase expression in a novel lung cancer ex vivo model - role of tumor stroma cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples