To identify transcriptional targets altered in the embryonic heart after exposure to TCE, and possible protective effects of folate, we used DNA microarray technology to profile gene expression in embryonic mouse hearts with maternal TCE exposure and dietary changes in maternal folate. Results: Exposure to low doses of TCE (10ppb) caused extensive alterations in transcripts encoding proteins involved in transport, ion channel, transcription, differentiation, cytoskeleton, cell cycle and apoptosis. Exogenous folate did not offset the effects of TCE exposure on normal gene expression and both high and low levels of folate produced additional significant changes in gene expression. Conclusions: A mechanism where TCE induces a folate deficiency does not explain altered gene expression patterns in the embryonic mouse heart. The data further suggest that use of folate supplementation, in the presence of this toxin, may be detrimental and non-protective of the developing embryo.
Gene expression profiling in the fetal cardiac tissue after folate and low-dose trichloroethylene exposure.
Specimen part
View SamplesPollen tubes extend through pistil tissues and are guided to ovules where they release sperm for fertilization. Although pollen tubes can germinate and elongate in a synthetic medium, their trajectory is random and their growth rates are slower compared to growth in pistil tissues. Furthermore, interaction with the pistil renders pollen tubes competent to respond to guidance cues secreted by specialized cells within the ovule. The molecular basis for this potentiation of the pollen tube by the pistil remains uncharacterized.
Penetration of the stigma and style elicits a novel transcriptome in pollen tubes, pointing to genes critical for growth in a pistil.
Specimen part
View SamplesMicroarray Analysis of Space-flown Murine Thymus Tissue Reveals Changes in Gene Expression Regulating Stress and Glucocorticoid Receptors. We used microarrays to detail the gene expression of space-flown thymic tissue and identified distinct classes of up-regulated genes during this process. We report here microarray gene expression analysis in young adult C57BL/6NTac mice at 8 weeks of age after exposure to spaceflight aboard the space shuttle (STS-118) for a period of 13 days. Upon conclusion of the mission, thymus lobes were extracted from space flown mice (FLT) as well as age- and sex-matched ground control mice similarly housed in animal enclosure modules (AEM). mRNA was extracted and an automated array analysis for gene expression was performed. Examination of the microarray data revealed 970 individual probes that had a 1.5 fold or greater change. When these data were averaged (n=4), we identified 12 genes that were significantly up- or down-regulated by at least 1.5 fold after spaceflight (p0.05). Together, these data demonstrate that spaceflight induces significant changes in the thymic mRNA expression of genes that regulate stress, glucocorticoid receptor metabolism, and T cell signaling activity. These data explain, in part, the reported systemic compromise of the immune system after exposure to the microgravity of space.
Microarray analysis of spaceflown murine thymus tissue reveals changes in gene expression regulating stress and glucocorticoid receptors.
Specimen part
View SamplesHypoxia, which characterizes most tumor tissues, can alter the function of different immune cell types, favoring tumor escape mechanisms. In this study, we show that hypoxia profoundly acts on NK cells by influencing their transcriptome, affecting their immunoregulatory functions, and changing the chemiotactic responses of different NK cell subsets.
Hypoxia Modifies the Transcriptome of Human NK Cells, Modulates Their Immunoregulatory Profile, and Influences NK Cell Subset Migration.
Specimen part
View SamplesTh17 cells are believed to be a critical cell population for driving autoimmune diseases. However, environmental factors that are directly related to the development of Th17 cells are largely unknown.
Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells.
Specimen part
View Samplesp63 mutations have been associated with several human hereditary disorders characterized by ectodermal dysplasia such as EEC syndrome, ADULT syndrome and AEC syndrome . The location and functional effects of the mutations that underlie these syndromes reveal a striking genotype-phenotype correlation. Unlike EEC and ADULT that result from missense mutations in the DNA-binding domain of p63, AEC is solely caused by missense mutations in the SAM domain of p63. We report a study on the TAp63a isoform, the first to be expressed during development of the embryonic epithelia, and on its naturally occurring Q540L mutant derived from an AEC patient. To assess the effects of the Q540L mutation, we generated stable cell lines expressing TAp63a wt, DeltaNp63 alpha or the TAp63 alpha-Q540L mutant protein and used them to systematically compare the cell growth regulatory activity of the mutant and wt p63 proteins and to generate, by microarray analysis, a comprehensive profile of differential gene expression. We found that the Q540L substitution impairs the transcriptional activity of TAp63a and causes misregulation of genes involved in the control of cell growth and epidermal differentiation.
The Hay Wells syndrome-derived TAp63alphaQ540L mutant has impaired transcriptional and cell growth regulatory activity.
No sample metadata fields
View SamplesUridylation of diverse RNA species represents an emerging theme in post-transcriptional gene regulation. In the microRNA pathway, such modifications regulate small RNA biogenesis and stability in plants, worms and mammals. Here, we report the first uridylyltransferase that acts on small RNAs in Drosophila, which we refer to as Tailor. Tailor is the source for the majority of 3´ end-modifications in microRNAs and predominantly targets precursor-hairpins. Uridylation modulates the characteristic two-nucleotide 3´ overhangs of microRNA hairpins, which regulates processing by Dicer-1 and destabilizes RNA hairpins. Furthermore, Tailor preferentially uridylates mirtron-hairpins, thereby impeding the production of non-canonical microRNAs. Mirtron-selectivity is explained by unique primary sequence specificity of Tailor, selecting RNA substrates ending with a 3´ guanosine, a feature not previously observed for TUTases. In contrast to mirtrons, conserved Drosophila pre-miRNAs are significantly depleted in 3´ guanosine, thereby escaping regulatory uridylation. Our data support the hypothesis that evolutionary adaptation to pre-miRNA uridylation shapes the nucleotide composition of pre-miRNA 3´ ends. Hence, hairpin-uridylation may serve as a barrier for the de novo creation of miRNAs in Drosophila. Overall design: mRNA sequencing of Drosophila S2 cells (3-times; control libraries) and three biological replicates of S2 cells stably depleted of CG1091/Tailor by CRISPR/Cas9
Uridylation of RNA Hairpins by Tailor Confines the Emergence of MicroRNAs in Drosophila.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Intra-graft expression of genes involved in iron homeostasis predicts the development of operational tolerance in human liver transplantation.
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View SamplesComplications due to long-term administration of immunosuppressive therapy increase the morbidity and mortality of liver transplant recipients. Discontinuation of immunosuppressive drugs in recipients spontaneously developing operational tolerance could substantially lessen this burden. However, this strategy results in the development of rejection in a high proportion of recipients who require lifelong immunosuppression. Thus, there is a need to identify predictive factors of successful drug withdrawal and to define the clinical and histological outcomes of operationally tolerant liver recipients. Methods. We enrolled 102 stable liver transplant recipients in an immunosuppression withdrawal trial in which drugs were gradually discontinued over a 6-9 month period. Patients with stable graft function and no signs of rejection in a liver biopsy conducted 12 months after cessation of immunosuppressive therapy were considered operationally tolerant. Results. Out of the 98 recipients who completed the study, immunosuppression discontinuation was successful in 41 recipients and rejection occurred in 57. Rejection episodes were mild and were resolved in all cases. Development of tolerance was independently associated with time elapsed since transplantation, recipient age, and male gender. No histological damage was apparent in protocol biopsies performed after successful drug withdrawal.
Intra-graft expression of genes involved in iron homeostasis predicts the development of operational tolerance in human liver transplantation.
Age, Specimen part
View SamplesIn clinical organ transplantation complete cessation of immunosuppressive therapy can be successfully accomplished in selected recipients providing a proof-of-principle that allograft tolerance is attainable in humans. The intra-graft molecular pathways associated with human allograft tolerance, however, have not been comprehensively studied before. In this study we analyzed sequential liver tissue samples collected from liver recipients enrolled in a prospective multicenter immunosuppressive withdrawal clinical trial. Tolerant and non-tolerant recipients differed in the intra-graft expression of genes involved in the regulation of iron homeostasis.These results point to a critical role of iron homeostasis in the regulation of intra-graft alloimmune responses in humans and provide a set of novel biomarkers to conduct drug-weaning trials in liver transplantation.
Intra-graft expression of genes involved in iron homeostasis predicts the development of operational tolerance in human liver transplantation.
No sample metadata fields
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