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GSE63457
Mus musculus
20 Downloadable Samples
Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
The transcription factor farnesoid X receptor (FXR) governs bile acid and energy homeostasis, is involved in inflammation, and has protective functions in the liver. In the present study we investigated the effect of Fxr deficiency in mouse precision cut liver slices (PCLS) exposed to a model hepatotoxicant cyclosporin A (CsA). It was anticipated that Fxr deficiency could aggravate toxicity of CsA in PCLS and pinpoint to novel genes/processes regulated by FXR.
Publication Title
Cyclosporin A induced toxicity in mouse liver slices is only slightly aggravated by Fxr-deficiency and co-occurs with upregulation of pro-inflammatory genes and downregulation of genes involved in mitochondrial functions.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Background: Studies in mice have shown that PPAR is an important regulator of lipid metabolism in liver and a key transcription factor involved in the adaptive response to fasting. However, much less is known about the role of PPAR in human liver. Here we set out to study the function of PPAR in human liver via analysis of whole genome gene regulation in human liver slices treated with the PPAR agonist Wy14643.
Publication Title
The impact of PPARα activation on whole genome gene expression in human precision cut liver slices.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject, Time
View Samples- Homo sapiens
- 127 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Compounds with direct immunotoxic properties, including metals, mycotoxins, agricultural pesticides and industrial chemicals, form potential human health risks due to exposure through food, drinking water, and the environment. Insights into the mechanisms of action are currently lacking for the majority of these direct immunotoxicants. Therefore, the present work aimed to gain insights into the molecular mechanisms underlying direct immunotoxicity. To this end, we assessed in vitro the effects of 31 test compounds on the transcriptome of the human Jurkat T cell line. These compounds included direct immunotoxicants, immunosuppressive drugs with different mode of actions, and non-immunotoxic control chemicals. Pathway analysis of the microarray data allowed us to identify canonical pathways and Gene Ontology processes that were transcriptionally regulated in common by immunotoxicants (i) with structural similarities, such as the tributyltins TBTC and TBTO that activated the retinoic acid / X receptor (RAR / RXR) signaling pathway, and (ii) without structural similarities, such as As2O3, DBTC, diazinon, MeHg, ochratoxin A, S9 treated ochratoxin A, S9 treated cyclophosphamide, and S9 treated benzo[a]pyrene, that activated unfolded protein response, and FTY720, lindane, and propanil, that activated the cholesterol biosynthesis pathway. In addition, processes uniquely affected by individual immunotoxicants were identified, such as the induction of Notch receptor signaling and the down regulation of acute phase response genes by ochratoxin A. These findings were validated by quantitative Real-Time PCR (Q-RT-PCR) analysis of genes involved in these processes. Our study indicated that diverse modes of action are involved in direct immunotoxicity and that a set of pathways or genes, rather than one single gene can be used to screen compounds for direct immunotoxicity.
Publication Title
Toxicogenomics-based identification of mechanisms for direct immunotoxicity.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Osteoarthritis (OA) of the hand is a common disease resulting in pain and impaired function. The pathogenesis of hand OA (HOA) is elusive and models to study it have not been described so far. Culture of chondrocytes is a model to study the development of cartilage degeneration, which is a hallmark of OA and well established in OA of the knee and hip. In the current study we investigated the feasibility human chondrocyte culture derived from proximal interphalangeal (PIP) finger joints of dissecting room cadavers. Index and middle fingers without signs of osteoarthritis were obtained from 30 cadavers using two different protocols. Hyaline cartilage from both articulating surfaces of the proximal interphalangeal (PIP) joint was harvested and digested in collagenase. Cultured chondrocytes were monitored for contamination, viability, and expression of chondrocyte specific genes. Chondrocytes derived from knee joints of the cadavers were cultured under identical conditions. Gene expression comparing chondrocytes from PIP and knee joints was carried out using Affymetrix GeneChip Human 2.0 ST arrays. The resulting differentially expressed genes were validated by real-time PCR and immunohistochemistry.Chondrocytes harvested up to 101 hours after death of the donors were viable. mRNA expression of collagen 2A1, aggrecan and Sox9 was significantly higher in chondrocytes as compared to cultured fibroblasts. Comparison of gene expression by chondrocytes from PIP and knee joints yielded 528 differentially expressed genes. Chondrocytes from the same joint region had a higher grade of similarity than chondrocytes of the same individual. These results were validated using real-time PCR and immunohistochemistry.We demonstrate for the first time a reliable method for culture of chondrocytes derived from PIP joints. PIP chondrocytes show a specific gene expression pattern and could be used as tool to study cartilage degeneration in HOA.
Publication Title
Chondrocyte cultures from human proximal interphalangeal finger joints.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 2000
Description
Somatic mutations in calreticulin (CALR) are present in approximately 40% of patients with myeloproliferative neoplasms (MPN). However, the mechanism by which mutant CALR is oncogenic is unknown. Here, we demonstrate that a megakaryocytic-specific MPN phenotype is induced when mutant CALR is over-expressed in mice and that the thrombopoietin receptor, MPL is required for mutant CALR driven transformation. Whole transcriptome analysis reveals enrichment of STAT signatures in mutant CALR transformed cells and JAK2 inhibitor treatment abrogates STAT activation. Employing extensive mutagenesis-based structure-function analysis we demonstrate that the positively charged amino acids within the mutant CALR C-terminus are required for cellular transformation through facilitating physical interaction between mutant CALR and MPL. Together, our findings elucidate a novel mechanism of cancer pathogenesis. Overall design: Transcriptomes derived from BA/F3-MPL cells transformed with human wild-type CALR, human mutant CALR 52bp del, or Empty vector, at time zero (t0) and 24 hours (t24) after IL3-withdrawal culture were generated by deep sequencing, two replicas, by HiSeq2000.
Publication Title
Mutant Calreticulin Requires Both Its Mutant C-terminus and the Thrombopoietin Receptor for Oncogenic Transformation.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
ERRa and ERRg are essential transcriptional regulators of cardiac metabolism and functions. Here we extend our previous studies by analyzing the transcriptome changes in ERRa/ERRg KO hearts Overall design: RNA from 16-day-old mouse hearts were used. 2-3 mice per sample, 2 samples per genotype, 4 genotypes (aHetgWT, aHetgKO, aKOgWT, aKOgKO)
Publication Title
Single-nucleus transcriptomic survey of cell diversity and functional maturation in postnatal mammalian hearts.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A summary of the work associated to these microarrays is the following:
Publication Title
Role of caveolin 1, E-cadherin, Enolase 2 and PKCalpha on resistance to methotrexate in human HT29 colon cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To elucidate the molecular pathways that modulate renal cyst growth in autosomal dominant polycystic kidney disease (ADPKD)
Publication Title
Systems biology of autosomal dominant polycystic kidney disease (ADPKD): computational identification of gene expression pathways and integrated regulatory networks.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Pyrazinamide (PZA) is one of the first line antibiotics used for the treatment of tuberculosis (TB). we have used human monocyte and a mouse model of pulmonary TB to investigate whether treatment with PZA, in addition to its known anti-mycobacterial properties, modulate the host immune response during Mycobacterium tuberculosis (Mtb) infection.
Publication Title
Host targeted activity of pyrazinamide in Mycobacterium tuberculosis infection.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The receptor-interacting protein-associated ICH-1/CED-3 homologous protein with a death domain (Raidd) functions as a dual adaptor protein due to its bipartite nature, and is therefore thought to be a constituent of different multiprotein complexes including the PIDDosome, where it connects the cell death-related protease, Caspase-2, with the p53-induced protein with a death domain 1 (Pidd1). As such, Raidd has been implicated in DNA-damage-induced apoptosis as well as in tumor suppression, the latter based on its role as a direct activator of Caspase-2, known to delay lymphomagenesis caused by overexpression of c-Myc or loss of ATM kinase. As loss of Caspase-2 leads to an acceleration of tumor onset in the E-Myc mouse model we set out to interrogate the role of Raidd in this process in more detail. Our data obtained analyzing E-Myc/Raidd-/- mice indicate that Raidd is unable to protect from c-MYC-driven lymphomagenesis. Similarly, we failed to observe an effect of Raidd-deficiency on thymic lymphomagenesis induced by y-irradiation or fibrosarcoma development driven by 3-methylcholanthrene. The role of Caspase-2 as a tumor suppressor can therefore be uncoupled from its ability to interact and auto-activate upon binding to Raidd. Further, we provide supportive evidence that the tumor suppressive role of Caspase-2 is related to maintaining genomic integrity and allowing efficient p53-mediated signaling. Overall, our findings suggest that Raidd, although described to be the key-adapter allowing activation of the tumor suppressor Caspase-2, fails to suppress tumorigenesis in vivo.
Publication Title
The tumor-modulatory effects of Caspase-2 and Pidd1 do not require the scaffold protein Raidd.
Sample Metadata Fields
No sample metadata fields
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