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GSE43891
Mus musculus
14 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Impaired neutrophil function in 24p3 null mice contributes to enhanced susceptibility to bacterial infections.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Lipocalin 24p3 (24p3) is a neutrophil secondary granule protein. 24p3 is also a siderocalin, which binds several bacterial siderophores. It was therefore proposed that synthesis and secretion of 24p3 by stimulated macrophages or release of 24p3 upon neutrophil degranulation sequesters iron-laden siderophores to attenuate bacterial growth. Accordingly, 24p3-deficient mice are susceptible to bacterial pathogens whose siderophores would normally be chelated by 24p3. Specific granule deficiency (SGD) is a rare congenital disorder characterized by complete absence of proteins in secondary granules. Neutrophils from SGD patients, who are prone to bacterial infections, lack normal functions but the potential role of 24p3 in neutrophil dysfunction in SGD is not known. Here we show that neutrophils from 24p3-deficient mice are defective in many neutrophil functions. Specifically, neutrophils in 24p3-deficient mice do not extravasate to sites of infection and are defective for chemotaxis. A transcriptome analysis revealed that genes that control cytoskeletal reorganization are selectively suppressed in 24p3-deficient neutrophils. Additionally, small regulatory RNAs (miRNAs) that control upstream regulators of cytoskeletal proteins are also increased in 24p3-deficient neutrophils. Further, 24p3-deficient neutrophils failed to phagocytose bacteria, which may account for the enhanced sensitivity of 24p3-deficient mice to both intracellular (Listeria monocytogenes) and extracellular (Candida albicans, Staphylococcus aureus) pathogens. Interestingly, Listeria does not secrete siderophores and additionally, the siderophore secreted by Candida is not sequestered by 24p3. Therefore, the heightened sensitivity of 24p3-deficient mice to these pathogens is not due to sequestration of siderophores limiting iron availability, but is a consequence of impaired neutrophil function.
Publication Title
Impaired neutrophil function in 24p3 null mice contributes to enhanced susceptibility to bacterial infections.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Many symptoms associated with allergic asthma result from the sequelae of type 2 inflammation. Interleukin (IL)-25 promotes type 2 inflammatory responses, and T2M cells represent an IL-4 and IL-13 producing granulocytic IL-25 responsive population.
Publication Title
Interleukin-25 induces type 2 cytokine production in a steroid-resistant interleukin-17RB+ myeloid population that exacerbates asthmatic pathology.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Biliary atresia (BA) is a rare cholestatic disease of unknown etiology that affects infants and shows an incidence of 1 out of 18,000 live births in Europe (1). The first therapeutic option is a timely performed portoenterostomy. However, the majority of patients suffer from a progressive inflammatory process, which leads to complete destruction of the extra- and intrahepatic biliary system followed by end-stage liver cirrhosis. Hence, BA is the leading indication for pediatric liver transplantation worldwide (2, 3). To understand the pathogenesis of the disease and improve theoutcome of BA patients, research has focused on the inflammatory process in liver and bile ducts, in which several factors are remarkably elevated, such as activated CD4 and CD8 T-cells, TNF alpha,IFN alpha and other proinflammatory TH1 cytokines (3-8). By the time of diagnosis, however, the disease has already reached an advanced state, characterized by the complete obstruction of the extrahepatic bile ducts with impaired bile flow and fibrosis or cirrhosis of the liver. Therefore, studies in humans focusing on the trigger mechanism of BA are limited due to the paucity of liver and availability of bile duct tissue for research. One infectious animal model has been developed, in which newborn Balb/c mice exclusively show the experimental BA phenotype after infection with rhesus rotavirus (RRV) (9, 10). This model allows the analysis of the inflammatory reactions in liver and bile ducts at early steps in the development of bile duct atresia (11-20). Furthermore, inbred mouse strains have been shown to have a different susceptibility for the development of experimental BA, suggesting that Balb/c mice have an immunological gap responsible for disease progression (10, 12). The aim of this study was to identify key genes responsible for the BA phenotype by comparing the transcriptomes at an early time point after virus infection, i.e. before bile duct atresia, between two mouse strains with different susceptibilities to BA. Differences in the virus titration and the clinical course of infected mice were analyzed, and variations in the hepatic gene response assessed by comparative microarray assays were correlated to variances in the hepatic inflammatory reaction.
Publication Title
Susceptibility to experimental biliary atresia linked to different hepatic gene expression profiles in two mouse strains.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 24 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Exposure to environmental contaminants can disrupt normal development of the early vertebrate skeleton. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) impairs craniofacial skeletal development across many vertebrate species and its effects are especially prominent in early life stages of fish. TCDD activates the aryl hydrocarbon receptor (AHR), a transcription factor that mediates most if not all TCDD responses. We investigated the transcriptional response in the developing zebrafish jaw following TCDD exposure using DNA microarrays. Zebrafish larvae were exposed to TCDD at 96 h postfertilization (hpf) and jaw cartilage tissue was harvested for microarray analysis at 1, 2, 4 and 12 h postexposure (hpe). Numerous chondrogenic transcripts were misregulated by TCDD in the jaw. Comparison of transcripts altered by TCDD in jaw with transcripts altered in embryonic heart showed that the transcriptional responses in the jaw and the heart were strikingly different. Sox9b, a critical chondrogenic transcription factor, was the most significantly reduced transcript in the jaw. We hypothesized that the TCDD reduction of sox9b expression plays an integral role in affecting formation of the embryonic jaw. Morpholino knock down of sox9b expression demonstrated that partial reduction of sox9b expression alone was sufficient to produce a TCDD-like jaw phenotype. Heterozygous sox9b deletion mutant embryos were sensitized to TCDD. Lastly, embryos injected with sox9b mRNA and then exposed to TCDD blocked TCDD-induced jaw toxicity in approximately 14% of sox9b-injected embryos. These results suggest that reduced sox9b expression in TCDD-exposed zebrafish embryos contributes to jaw malformation.
Publication Title
Aryl hydrocarbon receptor-mediated down-regulation of sox9b causes jaw malformation in zebrafish embryos.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Retinal detachment is a major cause of blindness due to penetrating trauma and ocular inflammation, and is often observed in many patients following cataract extraction surgery. When the retinal photoreceptors detach from their epithelium, stress signals and apoptotic pathways are initiated that will lead to loss of vision, however accelerating the reattachment of these cells can prevent photoreceptor death and subsequent vision loss. To determine the genes involved in this process, we performed a microarray screen using a mouse model or retinal detachment in conjunction with a P2Y2 agonist previously demonstrated to hasten retinal reattachment.
Publication Title
Expression profiling after retinal detachment and reattachment: a possible role for aquaporin-0.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Irritant contact dermatitis (ICD) pathogenesis is not completely understood and the genes participating in the epidermal response towards chemical irritants are only partly known. It is commonly accepted that different irritants have different mechanisms of action in the development of ICD. To define the differential molecular events induced in the epidermis by different irritants, we collected sequential biopsies (, 4 and 24 hours after a single exposure and at day 11 after repeated exposure) from human volunteers exposed to sodium lauryl sulphate (SLS) or nonanoic acid (NON). Gene expression analysis using high-density oligonucleotide microarrays revealed essentially different pathway responses h after exposure: NON transiently induced the IL-6 pathway as well as a number of mitogen activated signalling cascades including ERK and growth factor receptor signalling, whereas SLS transiently downregulated cellular energy metabolism pathways. Differential expression of the cyclooxygenase-2 and matrix metalloproteinase 3 transcripts was confirmed immunohistochemically. After cumulative exposure, 883 genes were differentially expressed while 26 suggested common biomarkers were identified . In conclusion, we bring new insights into two hitherto less well elucidated phases of skin irritancy: the very initial as well as the late phase after single and cumulative exposure, respectively.
Publication Title
Genome-wide expression analysis of human in vivo irritated epidermis: differential profiles induced by sodium lauryl sulfate and nonanoic acid.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Background: The terminal duct lobular unit (TDLU) is the most dynamic structure in the human breast and the putative site of origin of human breast cancer. Although stromal cells contribute to a specialized microenvironment in many organs, this component remains largely understudied in the human breast. We here demonstrate the impact on epithelium of two lineages of breast stromal fibroblasts, one of which accumulates in the TDLU while the other resides outside the TDLU in the interlobular stroma. Methods: The two lineages are prospectively isolated by FACS based on different expression levels of CD105 and CD26. The characteristics of the two fibroblast lineages are assessed by immunocytochemical staining and gene expression analysis. The differentiation capacity of the two fibroblast populations is determined by exposure to specific differentiating conditions followed by analysis of adipogenic and osteogenic differentiation. To test whether the two fibroblast lineages are functionally imprinted by their site of origin, single cell sorted CD271low/MUC1high normal breast luminal epithelial cells are plated on fibroblast feeders for the observation of morphological development. Epithelial structure formation and polarization is shown by immunofluorescence and digitalized quantification of immunoperoxidase stained cultures. Results: Lobular fibroblasts are CD105high/CD26low while interlobular fibroblasts are CD105low/CD26high. Once isolated the two lineages remain phenotypically stable and functionally distinct in culture. Lobular fibroblasts have properties in common with bone marrow derived mesenchymal stem cells and they specifically convey growth and branching morphogenesis of epithelial progenitors. Conclusions: Two distinct functionally specialized fibroblast lineages exist in the normal human breast, of which the lobular fibroblasts have properties in common with mesenchymal stem cells and support epithelial growth and morphogenesis. We propose that lobular fibroblasts constitute a specialized microenvironment for human breast luminal epithelial progenitors, i.e. the putative precursors of breast cancer.
Publication Title
Evidence of two distinct functionally specialized fibroblast lineages in breast stroma.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 48 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Retinoic acid (RA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin activate distinct ligand-dependent transcription factors, and both cause cardiac malformation and heart failure in zebrafish embryos. We hypothesized that they cause this response by hyperactivating a common set of genes critical for heart development. To test this, we used microarrays to measure transcripts changes in hearts isolated from zebrafish embryos 1,2,4 and 12 h after exposure to 1M RA. We used hierarchical clustering to compare the transcriptional responses produced in the embryonic heart by RA and TCDD. We could identify no early responses in common between the two agents. However, at 12 h both treatments produced a dramatic downregulation of a common cluster of cell cycle progression genes, which we term the Cell Cycle Gene Cluster (CCGC). This was associated with a halt in heart growth. These results suggest that RA and TCDD ultimately trigger a common transcriptional response associated with heart failure, but not through the direct activation of a common set of genes. Among the genes rapidly induced by RA was Nr2F5, a member of the COUP-TF family of transcription repressors. We found that induction of Nr2F5 was both necessary and sufficient for the cardiotoxic response to RA.
Publication Title
Comparative genomics identifies genes mediating cardiotoxicity in the embryonic zebrafish heart.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The experiment aims to identify mRNAs illustrating the unique nature of the gd T-cell subtype
Publication Title
Human Vδ2 T cells are a major source of interleukin-9.
Sample Metadata Fields
Specimen part
View Samples