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GSE14024
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The insulin-like growth factor (IGF) axis is an important signaling pathway in the growth and survival of many cell types and has been implicated in multiple aspects of cancer progression from tumorigenesis to metastasis. The multiple roles of IGF signaling in cancer suggest that selective inhibition of the pathway might yield clinically effective therapeutics. Here we describe A-928605, a novel small molecule inhibitor of the receptor tyrosine kinase responsible for IGF signal transduction. This small molecule is able to abrogate activation of the pathway as shown by effects on the target and downstream effectors and is shown to be effective at inhibiting the proliferation of an oncogene addicted tumor model cell line (CD8-IGF1R 3T3) both in vitro and in vivo.
Publication Title
Reversal of oncogene transformation and suppression of tumor growth by the novel IGF1R kinase inhibitor A-928605.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Epigenetic code modifications by histone deacetylase inhibitors (HDACi) have recently been proposed as potential new therapies for hematological malignancies. Chronic Lymphocytic Leukemia (CLL) remains incurable despite the introduction of new treatments. CLL cells are characterized by an apoptosis defect rather than excessive proliferation, but proliferation centers have been found in organs such as bone marrow and lymph nodes.
Publication Title
Antileukemic activity of valproic acid in chronic lymphocytic leukemia B cells defined by microarray analysis.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
It is now well established that bone marrow (BM) constitutes a microenvironment required for differentiation. Bone marrow mesenchymal stromal cells (BM-MSCs) strongly support MM cell growth, by producing a high level of Interleukin-6 (IL-6), a major MM cell growth factor. BM-MSCs also support osteoclastogenesis and angiogenesis. Previous studies have suggested that the direct (VLA-4, VCAM-1, CD44, VLA-5, LFA-1, syndecan-1,) and indirect interactions (soluble factors) between MM plasma cells and BM-MSCs result in constitutive abnormalities in BM-MSCs. In particular, MM BM-MSCs express less CD106 and fibronectin and more DKK1, IL-1 and TNF- as compared with normal BM-MSCs. In order to gain a global view of the differences between BM-MSCs from MM patients and healthy donors, we used gene expression profiling to identify genes associated to the transformation of MM BM-MSCs.
Publication Title
Evidences of early senescence in multiple myeloma bone marrow mesenchymal stromal cells.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
Islets are known to respond to changes in ambient glucose. To quantify the transcriptome-wide changes in ambient glucose, we compared transcriptome of islets exposed to low and high glucose. Overall design: Isolated islets from wild type male mice. Islets from adult males were pooled, cultured overnight in RPMI containing 11 mM glucose. The next day, all islets were starved in RPMI containing 2.8 mM glucose for 2 hours before stimulation with 2.8 mM glucose or 16.8 mM glucose for 12 hours. Islets were lysed in Trizol for RNA isolation and library construction.
Publication Title
The transcriptional landscape of mouse beta cells compared to human beta cells reveals notable species differences in long non-coding RNA and protein-coding gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Comparison of Chronic Lymphocytic Leukemia patients expressing high or low levels of ZAP70 mRNA: prognostic factors and interaction with the microenvironment.
Publication Title
Gene expression profiling reveals differences in microenvironment interaction between patients with chronic lymphocytic leukemia expressing high versus low ZAP70 mRNA.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
Rodent models are widely used to study diabetes. Yet, significant gaps remain in our understanding of mouse islet physiology. We generated comprehensive transcriptomes of mouse delta, beta and alpha cells using two separate triple transgenic mouse models generated for this purpose. This enables systematic comparison across thousands of genes between the three major endocrine cell types of the islets of Langerhans whose principal hormones control nutrient homeostasis. Overall design: FACS purified delta or alpha cells and beta cells from the same islets. Islets were isolated from triple transgenic offspring of a cross between mIns1-H2b-mCherry (Jax # 028589) and either Sst-Cre (delta) or Gcg-cre (alpha) cells and a floxed YFP allele to label delta or alpha cells, respectively. Islets from replicate groups of 10 to 12 triple transgenic animals for each group were pooled by sex to obtain sufficient material. Pooled islets were dissociated, sorted and collect in Trizol for RNA isolation and library construction.
Publication Title
Comprehensive alpha, beta and delta cell transcriptomes reveal that ghrelin selectively activates delta cells and promotes somatostatin release from pancreatic islets.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Sus scrofa
- 18 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Enterotoxigenic Escherichia coli (ETEC) strains that produce both heat-stable (ST) and heat-labile (LT) enterotoxins cause severe post-weaning diarrhea in piglets. However, the relative importance of the individual enterotoxins to the pathogenesis of ETEC infection is poorly understood. In this study, we investigated the effect on virulence of an F4+ ETEC strain when removing some or all of its enterotoxins. Several isogenic mutant strains were constructed that lack the expression of LT in combination with one or both types of ST enterotoxins (STa and/or STb). Host early immune responses induced by these mutant strains 4h after infection were compared to the wild type strain GIS26 (O149:F4ac+, LT+ STa+ STb+). At the same time, the immune response of this wild type ETEC strain was compared to the mock-infected control, demonstrating the expression of porcine inflammatory response genes. For these purposes, the small intestinal segment perfusion (SISP) technique and microarray analysis were used and results were validated by qRT-PCR. We also measured net fluid absorption of pig small intestinal mucosa 4h after infection with wild type ETEC, the mutant strains and PBS (mock-infected). These data indicate an important role for STb in inducing small intestinal secretion early after infection. The microarray analysis of the different mutant strains also revealed an important role for STb in ETEC-induced immune response by the significant differential regulation of immune mediators like matrix metalloproteinase 3, interleukin 1 and interleukin 17. We conclude that STb can play a prominent role in ETEC-induced secretion and early immune response.
Publication Title
Role of heat-stable enterotoxins in the induction of early immune responses in piglets after infection with enterotoxigenic Escherichia coli.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Sus scrofa
- 48 Downloadable Samples
- Porcine Gene 1.1 ST Array (porgene11st)
Description
An early settlement of a complex gut microbiota can protect against gastro-intestinal dysbiosis, but the effects of neonatal microbiota colonization on the gut barrier upon the further encounter of favorable bacteria or not, are largely unknown.
Publication Title
Molecular networks affected by neonatal microbial colonization in porcine jejunum, luminally perfused with enterotoxigenic Escherichia coli, F4ac fimbria or Lactobacillus amylovorus.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina HiSeq 2000
Description
Reporter genes integrated into the genome are a powerful tool to reveal effects of regulatory elements and local chromatin context on gene expression. However, so far such reporter assays have been of low throughput. Here we describe a multiplexing approach for the parallel monitoring of transcriptional activity of thousands of randomly integrated reporters. More than 27,000 distinct reporter integrations in mouse embryonic stem cells, obtained with two different promoters, show ~1,000-fold variation in expression levels. Data analysis indicates that lamina-associated domains act as attenuators of transcription, likely by reducing access of transcription factors to binding sites. Furthermore, chromatin compaction is predictive of reporter activity. We also found evidence for cross-talk between neighboring genes, and estimate that enhancers can influence gene expression on average over ~20 kb. The multiplexed reporter assay is highly flexible in design and can be modified to query a wide range of aspects of gene regulation. Overall design: mRNA profiles of 11 mouse embryonic cell lines each harboring multiple barcoded reporter constructs with mouse PGK promoter integrated at random positions in the genome, single replicate.
Publication Title
Chromatin position effects assayed by thousands of reporters integrated in parallel.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Repair of injured muscle involves repair of injured myofibers through the involvement of dysferlin and its interacting partners, including annexin. Studies with mice and patients have established that dysferlin deficit leads to chronic inflammation and adipogenic replacement of the diseased muscle. However, longitudinal analysis of annexin deficit on muscle pathology and function is lacking. Here we show that unlike annexin A1, but similar to dysferlin, lack of annexin A2 (AnxA2) causes poor myofiber repair and progressive weakening with age. However, unlike dysferlin-deficient muscle, AnxA2-deficient muscles do not exhibit chronic inflammation or adipogenic replacement. Deletion of AnxA2 in dysferlin deficient mice reduces inflammation, adipogenic replacement, and loss in muscle function caused by dysferlin deficit. These results show that: a) AnxA2 facilitates myofiber repair, b) chronic inflammation and adipogenic replacement of dysferlinopathic muscle requires AnxA2, and c) inhibiting AnxA2-mediated inflammation is a novel therapeutic avenue for dysferlinopathy.
Publication Title
Annexin A2 links poor myofiber repair with inflammation and adipogenic replacement of the injured muscle.
Sample Metadata Fields
Age, Specimen part
View Samples