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GSE17354
Homo sapiens
13 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene transfer into HSCs by gammaretroviral vectors (RV) is an effective treatment for inherited blood disorders, although potentially limited by the risk of insertional mutagenesis. We evaluated the genomic impact of RV integration in T-lymphocytes from adenosine deaminase (ADA)-Severe combined immunodeficiency (SCID) patients 10 to 30 months after infusion of autologous, genetically-corrected CD34+ cells. Expression profiling on ex vivo T-cell bulk population revealed no difference with respect to healthy controls. To assess the effect of vector integration on gene expression at the single cell level, primary T-cell clones were isolated from two patients. T-cell clones harboured either one or two vector copies per cell and displayed partial to full correction of ADA expression, purine metabolism and TCR-driven functions. Analysis of retroviral integration sites (RIS) indicated a high diversity in T-cell origin, consistent with the polyclonal TCR-Vbeta repertoire. Quantitative transcript analysis of 120 genes within a 200kb-window around RIS showed modest (2.8- to 5.2-fold) disregulation of 5.8% genes in 18.6% of the T-cell clones compared to controls. Nonetheless, affected clones maintained a stable phenotype and normal functions in vitro. These results confirm that RV-mediated gene transfer for ADA-SCID is safe, and provide crucial information for the development of future gene therapy protocols.
Publication Title
Integration of retroviral vectors induces minor changes in the transcriptional activity of T cells from ADA-SCID patients treated with gene therapy.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
17-estradiol (E2) exerts complex and context-dependent effects in pulmonary hypertension. In hypoxia-induced pulmonary hypertension (HPH), E2 attenuates lung vascular remodeling through estrogen receptor (ER)-dependent effects; however, ER target genes in the hypoxic lung remain unknown. In order to identify the genome regulated by the E2-ER axis in the hypoxic lung, we performed a microarray analysis in lungs from HPH rats treated with E2 (75 mcg/kg/d) ER-antagonist ICI182,780 (3 mg/kg/d). Untreated HPH rats and normoxic rats served as controls. Using a false discovery rate of 10%, we identified a significantly differentially regulated genome in E2-treated vs. untreated hypoxia rats. Genes most up-regulated by E2 encoded matrix metalloproteinase 8, S100 calcium binding protein A8, and IgA Fc receptor; genes most down-regulated by E2 encoded olfactory receptor 63, secreted frizzled-related protein 2, and thrombospondin 2. Several genes affected by E2 changed in the opposite direction after ICI182,780 co-treatment, indicating an ER-regulated genome in HPH lungs. The bone morphogenetic protein antagonist Grem1 (gremlin 1) was up-regulated by hypoxia, but found to be among the most down-regulated genes after E2 treatment. Gremlin 1 protein was reduced in E2-treated vs. untreated hypoxic animals, and ER-blockade abolished the inhibitory effect of E2 on Grem1 mRNA and protein. In conclusion, E2 ER-dependently regulates several genes involved in proliferative and inflammatory processes during hypoxia. Gremlin 1 is a novel target of the E2-ER axis in HPH. Understanding the mechanisms of E2 gene regulation in HPH may allow for selectively harnessing beneficial transcriptional activities of E2 for therapeutic purposes.
Publication Title
Estrogen receptor-dependent attenuation of hypoxia-induced changes in the lung genome of pulmonary hypertension rats.
Sample Metadata Fields
Treatment
View Samples- Gallus gallus
- 9 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
Basilar papillae (i.e.auditory epithelia) were isolated from 4-day-old chickens and sectioned into low, middle, and high frequency segments. RNA was isolated from each segment separately, amplified using a two-cycle approach, biotinylated, and hybridized to Affymetrix chicken whole-genome arrays.
Publication Title
Gene expression gradients along the tonotopic axis of the chicken auditory epithelium.
Sample Metadata Fields
Specimen part
View Samples- Gallus gallus
- 12 Downloadable Samples
- Affymetrix Chicken Gene 1.0 ST Array (chigene10st)
Description
Development of Pectoralis major has been investigated through gene expression analysis in comparing animals receiving a restricted diet in P and Ca (NC), a normal diet with sufficient level of P and Ca (PC), and a restricted diet supplemented with phytase (Phy1000).
Publication Title
Exploratory transcriptomic analysis in muscle tissue of broilers fed a phytase-supplemented diet.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 15 Downloadable Samples
- Bovine Gene 1.0 ST Array (bovgene10st)
Description
The aim of this study was to compare the transcriptome of the different regions of the oviduct between pregnant and cyclic heifers. After synchronizing crossbred beef heifers, those in standing oestrus (=Day 0) were randomly assigned to cyclic (non bred, n=6), or pregnant (artificially inseminated, n=11) groups. They were slaughtered on Day 3 and both oviducts from each animal were isolated and cut in half to separate ampulla and isthmus. Each portion was flushed to confirm the presence of an oocyte/embryo and was then opened longitudinally and scraped to obtain epithelial cells which were snap-frozen. Oocytes and embryos were located in the isthmus of the oviduct ipsilateral to the corpus luteum. Microarray analysis of oviductal cells revealed that proximity to the corpus luteum did not affect the transcriptome of the isthmus, irrespective of pregnancy status. However, 2287 genes were differentially expressed (P<0.01) between the ampulla and isthmus of the oviduct ipsilateral to the corpus luteum. Gene ontology revealed that the main biological processes overrepresented in the isthmus were synthesis of nitrogen, lipids, nucleotides, steroids and cholesterol as well as vesicle-mediated transport, cell cycle, apoptosis, endocytosis and exocytosis, whereas cell motion, motility and migration, DNA repair, calcium ion homeostasis, carbohydrate biosynthesis and regulation of cilium movement and beat frequency were overrepresented in the ampulla. In conclusion, large differences in gene expression were observed between the isthmus and ampulla that reflect morphological and functional characteristics of each segment.
Publication Title
Spatial differences in gene expression in the bovine oviduct.
Sample Metadata Fields
Specimen part
View Samples- Gallus gallus
- 41 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
This study aimed to characterize the transcriptomes of developing neurons from the chicken retina.
Publication Title
Single cell transcriptome profiling of developing chick retinal cells.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to detail the global programme of gene expression by circulating TCRVgamma9+ gamma delta T cells isolated from healthy individuals,tested either as resting cells or cells activated by phosphoantigen BrHPP and IL-2at an early(+6hrs) and a late (+7days) timepoint.
Publication Title
The gene expression profile of phosphoantigen-specific human γδ T lymphocytes is a blend of αβ T-cell and NK-cell signatures.
Sample Metadata Fields
Specimen part, Disease, Treatment, Subject, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Targeting protein kinase C (PKC) isoforms by the small molecule inhibitor enzastaurin has shown promising pre-clinical activity in a wide range of tumor cells. In this study, we further delineated its mechanism of action in multiple myeloma (MM) cells and found a novel role of b-catenin in regulating growth and survival of tumor cells. Specifically, inhibition of PKC leads to rapid accumulation of b-catenin by preventing the phosphorylation required for its proteasomal degradation. Microarray analysis and siRNA-mediated gene silencing in MM cells revealed that accumulated b-catenin activates early ER stress signaling via eIF2a, CHOP and p21, leading to immediate growth inhibition. Furthermore, accumulated b-catenin contributes to enzastaurin-induced cell death. Both sequential knock-down of b-catenin, c-Jun, and p73, as well as overexpression of b-catenin or p73 confirmed that accumulated b-catenin triggers c-Jun-dependent induction of p73, thereby conferring MM cell apoptosis. In summary, our data reveal a novel role of b-catenin in ER stress-mediated growth inhibition, and a new pro-apoptotic mechanism triggered by b-catenin upon inhibition of PKC isoforms. Moreover, we identify p73 as a potential novel therapeutic target in MM. Based on these and previous data, enzastaurin is currently under clinical investigation in a variety of hematologic malignancies including MM.
Publication Title
Targeting PKC: a novel role for beta-catenin in ER stress and apoptotic signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
mRNA expression in colon cancer tumores
Publication Title
Mice that express human interleukin-8 have increased mobilization of immature myeloid cells, which exacerbates inflammation and accelerates colon carcinogenesis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 82 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples