Filters
Technology
Platform
GSE73911
Mus musculus
16 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The tumor suppressor gene RASSF1A (Ras association domain family protein 1A) coding for a microtubule stabilizing protein is epigenetically silenced in most human cancers. As a binding partner of the kinases MST1 and MST2, the mammalian orthologues of the Drosophila Hippo kinase, RASSF1A is a potential regulator of the Hippo tumor suppressor pathway. RASSF1A shares these properties with the scaffold protein SAV1. The role of this pathway in human cancer has remained enigmatic because Hippo pathway components are rarely mutated. Rassf1a homozygous knockout mice developed liver tumors. However, heterozygous deletion of Sav1 or co-deletion of Rassf1a and Sav1 produced liver tumors with much higher efficiency than single deletion of Rassf1a. Analysis of RASSF1A binding partners by mass spectrometry identified the Hippo kinases MST1, MST2 and the oncogenic IkB kinase TBK1 as the most significantly enriched RASSF1A-interacting proteins. The transcriptome of Rassf1a-/- livers was more deregulated than that of Sav1+/- livers and the transcriptome of Rassf1a-/-, Sav1+/- livers was similar to that of Rassf1a-/- mice. We found that the levels of Tbk1 protein were substantially upregulated in livers lacking Rassf1a, and at the transcript level, factors regulating Tbk1 stability, including Usp2 and Dtx4, were also dysregulated. Furthermore, transcripts of several beta tubulin isoforms were increased in the Rassf1a-deficient liver genotypes presumably reflecting a role of Rassf1a as a tubulin-binding and microtubule-stabilizing protein. Our data suggest a multifactorial role of Rassf1a in suppression of liver carcinogenesis.
Publication Title
Analysis of Liver Tumor-Prone Mouse Models of the Hippo Kinase Scaffold Proteins RASSF1A and SAV1.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 33 Downloadable Samples
IonTorrentProton
Description
The type I JAK inhibitor ruxolitinib is approved for therapy of MPN patients but evokes resistance with longer exposure. Several novel type I JAK inhibitors were studied and we show that they uniformly induce resistance via a shared mechanism of JAK family heterodimer formation.Here we studied the expression profiles of SET2 cell lines persistent to several different type I JAK inhibitors in comparison to naive SET2 cells or in comparison to SET2 cells with acute exposure to ruxolitinib. Overall design: Analysis of RNA isolated from several type I JAK inhibitor SET2 cell lines in comparison to naïve SET2 cells
Publication Title
CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To determine a gene/molecular fingerprint of multiple myeloma (MM) endothelial cells (MMECs), also identifying some of the vascular mechanisms that govern the malignant progression from quiescent monoclonal gammopathy of undetermined significance (MGUS). A comparative gene expression profiling (GEP) was carried out on patient-derived MMECs and MGUS endothelial cells (MGECs) using the Affymetrix U133A Arrays. Expression of selective vascular markers were also validated by RT-PCR and immunoblotting analysis in primary cultures of ECs isolated from total bone marrow (BM)-mononuclear cells. Twenty-two genes were found differently expressed in MMECs compared to MGECs (with 14 down-regulated and 8 up-regulated), thus proving that molecular differences were maintained in vitro. Specific pathways analysis revealed transcriptional and protein expression changes for key regulators of extracellular matrix formation and bone remodeling, cell-adhesion, chemotaxis, angiogenesis, resistance to apoptosis, and cell-cycle regulation. Specifically, we focused on six of these genes (DIRAS3, SERPINF1, SRPX, BNIP3, IER3 and SEPW1), which were not previously functionally correlated to the overangiogenic phenotype of MMECs and disease activity. These data identified distinct EC gene expression profiles and some vascular phenotypes that could influence the remodeling of the BM-microenvironment in patients with active MM. A better understanding of the linkage between genetic and epigenetic events in MM tumor/ECs may contribute to the molecular classification of the disease, thereby identifying selective targets of more effective anti-vessel/stroma therapeutic strategies.
Publication Title
Gene expression profiling of bone marrow endothelial cells in patients with multiple myeloma.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 554 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Background: Strategies to improve long term renal allograft survival have been directed to recipient dependent mechanisms of renal allograft injury. In contrast, no such efforts have been made to optimize organ quality in the donor. In order to get insight into the deleterious gene pathways expressed at different time points during deceased kidney transplantation, transcriptomics was performed on kidney biopsies from a large cohort of deceased kidney transplants.
Publication Title
Hypoxia and Complement-and-Coagulation Pathways in the Deceased Organ Donor as the Major Target for Intervention to Improve Renal Allograft Outcome.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
RNA from two murine mesothelioma cell lines (AC29 and AB1) was extracted and hybridized to Affymetrix Microarrays to compare gene expression. Both mesothelioma cell lines were established following intraperitoneal introduction of crocidolite (asbestos) fibers (Davis et al. 1992) in CBA mice (AC29 cell line), and BALB/c mice (AB1).
Publication Title
Depletion of Tumor-Associated Macrophages with a CSF-1R Kinase Inhibitor Enhances Antitumor Immunity and Survival Induced by DC Immunotherapy.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Interactions between Chronic Lymphocytic Leukemia B-cells (CLL B-cells) and the microenvironment (ME) play a major function in the physiopathology of CLL. Extracellular vesicles (EVs) (composed of exosomes and microparticles) have been shown to play an important role in cell communication. EVs, purified by ultracentrifugation from bone marrow mesenchymal stromal cells (BM-MSC) culture, were added to CLL B-cells. Microarray study highlighted 805 differentially expressed genes between CLL-B-cells cultured with and without EVs. Of these, CCL3/4, EGR1/2/3, MYC (involved in BCR pathway) were increased while pro-apoptotic genes like HRK were decreased. We showed for the first time the potential of EVs alone to induce gene expression modifications in CLL B-cell, notably in BCR and apoptosis pathways. We concluded that a substantial part of communication between CLL B-cells and BM-ME is mediated through EV.
Publication Title
Extracellular vesicles of bone marrow stromal cells rescue chronic lymphocytic leukemia B cells from apoptosis, enhance their migration and induce gene expression modifications.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 659 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
PDX tumors at various passages post first implantation in nude mice
Publication Title
High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
To understand how haploinsufficiency of progranulin (PGRN) protein causes frontotemporal dementia (FTD), we created induced pluripotent stem cells (iPSC) from patients carrying the GRNIVS1+5G>C mutation (FTD-iPSCs). FTD-iPSCs were fated to cortical neurons, the cells most affected in FTD and known to express PGRN. Although generation of neuroprogenitors was unaffected, their further differentiation into neurons, especially CTIP2-, FOXP2- or TBR1-TUJ1 double positive cortical neurons, was significantly decreased in FTD-neural progeny. Zinc finger nuclease-mediated introduction of PGRN cDNA into the AAVS1 locus corrected defects in cortical neurogenesis, demonstrating that PGRN haploinsufficiency causes inefficient cortical neuron generation. RNAseq analysis confirmed reversal of altered gene expression profile following genetic correction. Wnt signaling pathway, one of the top defective pathways in FTD-iPSC-derived neurons coupled with its reversal following genetic correction, makes it an important candidate. Therefore, we demonstrate for the first time that PGRN haploinsufficiency hampers corticogenesis in vitro. Overall design: We profiled 6 samples: two biological replicates for 3 conditions. Condition 1 consists of neuronal progeny derived from human Embryonic Stem Cells. Condition 2 consists of neuronal progeny derived from induced pluripotent stem cells generated from patients carrying PGRN mutation. Condition 3 consists of neuronal progeny derived from induced pluripotent stem cells generated from patients carrying PGRN mutation, genetically modified to correct the PGRN defect.
Publication Title
Restoration of progranulin expression rescues cortical neuron generation in an induced pluripotent stem cell model of frontotemporal dementia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To identify the CAR-, PXR- and PPAR-specific genome-wide expression changes, hepatocyte cultures from six individual donors were treated with the prototypical ligands for
Publication Title
Genomewide comparison of the inducible transcriptomes of nuclear receptors CAR, PXR and PPARα in primary human hepatocytes.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide promoter methylation analysis in neuroblastoma identifies prognostic methylation biomarkers.
Sample Metadata Fields
Treatment
View Samples