Microarray analyses provide a powerful approach to identify gene expression alterations following kidney transplantation. However, the heterogeneity of human kidney transplant specimens and the variation in sample preparation precludes conclusions regarding the underlying mechanisms of the observed alterations. We used a well defined experimental rat kidney transplantation model with consistent transplant and sample preparation procedures to analyze genome wide changes in gene expression after syngeneic (sTX) and allogeneic transplantation (aTX) four days after transplantation. Both interventions were associated with dramatic changes in gene expression. Genes and Pathways related to immune response were extremely up regulated after aTX. Several of the up regulated genes have been described by other groups and we are able to proof this in one study. But several genes are reported for the first time to be up regulated in expression after renal aTX. The function of these genes in acute rejection process has to be evaluated. On the other hand the up regulation of regulatory or protective genes indicates that regulatory mechanism are activated after aTX trying to down regulate the immune response or protect the tissue against the immune system. The study is capable to serve as a representative study in aTX mediated gene expression by covering the known transcriptional changes reported by other groups and identification of novel markers and pathways. Further analysis of the duplicated datasets by other groups can help for a better understanding of the mechanisms mediated by acute rejection and thereby increase the therapeutic threatment.
Activation of counter-regulatory mechanisms in a rat renal acute rejection model.
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View SamplesCyclosporin A induces expression of proapoptotic factors when cells are challenged by increased tonicity
Cyclosporin-A induced toxicity in rat renal collecting duct cells: interference with enhanced hypertonicity induced apoptosis.
Specimen part, Treatment
View SamplesAbnormal function of genes is at the root of most cancers, but heritable cancer syndromes account for a very small minority of all tumors in humans and domestic animals. The majority of cancers are sporadic, that is, they are not heritable in the strictest sense. Instead, sporadic cancers occur due to interactions of unknown intrinsic (heritable) and environmental factors that lead to malignant transformation and uncontrolled growth. Identification of heritable risk factors in sporadic human cancers is difficult because individual genetic backgrounds are very heterogeneous. To this end, individual genetic backgrounds of purebred dogs are more homogeneous, and dog breeds show different predilection to develop specific cancers. Here, we used genomic screens based on gene expression profiling to identify sets of genes that may contribute to the development of canine hemangiosarcoma, a relatively common endothelial sarcoma. Specific genes in a single breed (Golden Retrievers) are modulated by (or with) heritable risk traits, showing functional features that appear to modulate tumor behavior. Our results suggest these methods are suitable to identify genes that will enhance our understanding of how these cancers happen, as well as possible treatment targets that will improve outcomes of both human and canine cancer patients.
Innate immune response to influenza A virus in differentiated human alveolar type II cells.
Specimen part, Subject, Time
View SamplesMammalian nephrons are the physiological subunits of mammalian kidneys which consist of different highly apicobasally polarized epithelial cell types. In epithelial cells polarization is controlled by evolutionary conserved CRB, PAR, or SRIB complexes. Here, we focused on the role of Pals1/Mpp5 in the nephron. Pals1, a core component of the apical membrane determining CRB complex, is highly expressed in renal tubular epithelial and glomerular epithelial cells (podocytes). Surprisingly, haplo-deficient mice, lacking one Pals1/Mpp5 allele in the nephron developed a strong phenotype, accompanied by cyst formation and severe renal filtration barrier defects, which subsequently lead to death after 6-8 weeks. Supporting studies in Drosophila nephrocytes, and epithelial cell culture models elucidated the role of Pals1 as a dose dependent upstream regulator of the crosstalk between Hippo- and TGF-signaling during nephrogenesis.
Pals1 Haploinsufficiency Results in Proteinuria and Cyst Formation.
Specimen part
View SamplesMany tumors produce platelet-derived growth factor (PDGF)-DD, which promotes cellular proliferation, epithelial-mesenchymal transition, stromal reaction, and angiogenesis through autocrine and paracrine PDGFRß signaling. By screening a secretome library, we found that the human immunoreceptor NKp44 encoded by NCR2 and expressed on natural killer (NK) cells and innate lymphoid cells recognizes PDGF-DD. PDGF-DD engagement of NKp44 triggered NK cell secretion of IFN-? and TNF-a that induced tumor cell growth arrest. A distinctive transcriptional signature of PDGF-DD-induced cytokines and the downregulation of tumor cell cycle genes correlated with NCR2 and greater survival in glioblastoma. NKp44 expression in mouse NK cells controlled the dissemination of tumors expressing PDGF-DD more effectively than control mice, an effect enhanced by blockade of the inhibitory receptor CD96 or CpG-oligonucleotide treatment. Thus, whilst cancer cell production of PDGF-DD supports tumor growth and stromal reaction, it concomitantly activates innate immune responses to tumor expansion. Overall design: RNAseq of NK cell and tumor cell samples in reponse to various stimuli
Natural Killer Cells Control Tumor Growth by Sensing a Growth Factor.
Specimen part, Cell line, Treatment, Subject
View SamplesThe effect of PDGF-DD on the gene expression of human tonsil ILC1 is unknown. We used microarray to determine the transcriptional differences between unstimulated and PDGF-DD-stimulated human tonsil ILC1.
Natural Killer Cells Control Tumor Growth by Sensing a Growth Factor.
Specimen part
View SamplesIn the present study, transcript profiling was carried out in the liver samples from wk 5 of lactation in order to identify genes and pathways regulated by rumen-protected CLA during early lactation. The first wks after parturition represent a critical phase in the productive cycle of high-yielding dairy cows because the liver experiences pronounced metabolic and inflammatory stress which increases the risk to develop liver-associated diseases, such as fatty liver and ketosis.
Transcript profiling in the liver of early-lactating dairy cows fed conjugated linoleic acid.
Sex, Specimen part
View SamplesSMARCB1 (Snf5/Ini1/Baf47) is a potent tumor suppressor, the loss of which serves as the diagnostic feature in Malignant Rhabdoid Tumors (MRT) and Atypical Teratoid/Rhabdoid Tumors (AT/RT), two highly aggressive forms of pediatric neoplasms. Here, we restore Smarcb1 expression in cells derived from Smarcb1-deficient tumors which developed in Smarcb1-heterozygous p53-/- mice.
Loss of IGFBP7 expression and persistent AKT activation contribute to SMARCB1/Snf5-mediated tumorigenesis.
Specimen part, Cell line
View SamplesStudy of PBMC gene expression during the first 10 weeks of therapy with Pegylated-interferon-alfa2b (PegIntronTM) and ribavirin (administered by weight) in HCV patients.
Cyclic changes in gene expression induced by Peg-interferon alfa-2b plus ribavirin in peripheral blood monocytes (PBMC) of hepatitis C patients during the first 10 weeks of treatment.
Subject
View SamplesThis is an analysis of Caco-2 BBe cell spontaneous differentiation. JF2dR1-JF2dR4 = proliferating cells; JF8dR1-JF8dR4 = 4 d post-confluent; JF15dR1-JF15dR4 = 11 d pc, differentiated
Gene expression profiling of Caco-2 BBe cells suggests a role for specific signaling pathways during intestinal differentiation.
No sample metadata fields
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