Resistance to amebiasis is associated with a polymorphism in the leptin receptor. Previous studies demonstrated that humans with the ancestral Q223 leptin receptor allele were nearly four times less likely to be infected with Entamoeba histolytica than those carrying the mutant R223 allele. We hypothesized that the Q223 allele protected against E. histolytica via STAT3-mediated transcription of genes required for mucosal immunity. To test this, mice containing the humanized LEPR Q or R allele at codon 223 were intracecally infected with E. histolytica. Susceptibility to amebiasis was assessed, and cecal tissues analyzed for changes in gene expression. By 72 h post-challenge all Q223 mice had cleared E. histolytica, whereas 39% of 223R mice were infected. 37 genes were differentially expressed in response to infection at 72 h, including pro-inflammatory genes (CXCL2, calprotectin (S100A8/9), Pla2g7, Itbg2, and MMP9) and functions pertaining to the movement and activity of immune cells. A comparison at 12 h post-challenge of infected Q223 vs. R223 mice identified a subset of differentially-expressed genes, many of which were closely linked to leptin signaling. Further analyses indicated that the Q223 gene expression pattern was consistent with a suppressed apoptotic response to infection, while 223R showed increased cellular proliferation and recruitment. These studies are the first to illuminate the downstream effects of leptin receptor polymorphisms on intestinal infection by E. histolytica. As such, they are important for the insight that they provide to this previously uncharacterized mechanism of mucosal immunity. Resistance to amebiasis is associated with a polymorphism in the leptin receptor. Previous studies demonstrated that humans with the ancestral Q223 leptin receptor allele were nearly four times less likely to be infected with Entamoeba histolytica than those carrying the mutant R223 allele. We hypothesized that the Q223 allele protected against E. histolytica via STAT3-mediated transcription of genes required for mucosal immunity. To test this, mice containing the humanized LEPR Q or R allele at codon 223 were intracecally infected with E. histolytica. Susceptibility to amebiasis was assessed, and cecal tissues analyzed for changes in gene expression. By 72 h post-challenge all Q223 mice had cleared E. histolytica, whereas 39% of 223R mice were infected. 37 genes were differentially expressed in response to infection at 72 h, including pro-inflammatory genes (CXCL2, calprotectin (S100A8/9), Pla2g7, Itbg2, and MMP9) and functions pertaining to the movement and activity of immune cells. A comparison at 12 h post-challenge of infected Q223 vs. R223 mice identified a subset of differentially-expressed genes, many of which were closely linked to leptin signaling. Further analyses indicated that the Q223 gene expression pattern was consistent with a suppressed apoptotic response to infection, while 223R showed increased cellular proliferation and recruitment. These studies are the first to illuminate the downstream effects of leptin receptor polymorphisms on intestinal infection by E. histolytica. As such, they are important for the insight that they provide to this previously uncharacterized mechanism of mucosal immunity.
Effect of the leptin receptor Q223R polymorphism on the host transcriptome following infection with Entamoeba histolytica.
Specimen part, Time
View SamplesA subset of GC B cells that have stopped cycling, upregulated CD38 and downregulated BCL-6 is functionally verified as GC-derived memory B cell precursors (GC-MPs). RNA-seq analyses of the transcriptome were used to probe the developmental trajectory of these cells and their responses to IL-9, a cytokine that is found to drive the memory development from the GC. Overall design: Differential gene expression analyses between GC-MP cells and regular GC B cells in G1 phase (GC-MPP cells); Gene expression profiling of different GC subsets in comparison to memory B cells and plasma cells; acute effects of in vivo IL-9 or anti-IL-9 treatment on GC-MP or GC-MPP cells.
Germinal-center development of memory B cells driven by IL-9 from follicular helper T cells.
Specimen part, Cell line, Treatment, Subject
View SamplesImmune thrombocytopenia (ITP) is an autoimmune disease where platelets are destroyed prematurely. In the majority of children the disease resolves but in some it becomes chronic. To investigate whether the two forms of the disease are similar or separate entities we performed DNA microarray analysis of T-cells from newly diagnosed children and children with chronic ITP. We found complete separation of the expression files between the two forms of the disease. Furthermore, the gene expression of several cytokines differed between the two forms of the disease. This was also reflected in plasma with increased levels of IL-16 and TWEAK and lower levels of IL-4 in newly diagnosed compared with chronic ITP. Thus, our data indicate that the two forms of the disease may be separate entities.
Differences in gene expression and cytokine levels between newly diagnosed and chronic pediatric ITP.
Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features.
Sex, Age, Specimen part, Disease
View SamplesDifferential gene expression is assessed in substantia nigra and basal ganglia of neurodegenertion with brain iron accumulation cases (BIA) compared to matched normal controls (c).
Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features.
Sex, Age, Specimen part, Disease
View SamplesClear cell renal cell carcinoma (ccRCC), the major histotype of cancer derived from kidney, is lack of robust prognostic and/or predictive biomarker and powerful therapeutic target. We previously identified that follistatin-like protein 1 (FSTL1) was significantly down-regulated in ccRCC at the transcription level. In the present study, we characterized, for the first time, that FSTL1 immunostaining was selectively positive in the cytoplasm of distal convoluted tubules. The expression of FSTL1 was significantly lower in ccRCC tissues than in adjacent renal tissues (P<0.001), as measured using immunohistochemistry in 69 patients with paired specimens, and lower in most ccRCC cell lines than in human embryonic kidney cells, as measured by quantitative RT-PCR. Multivariate Cox regression analysis in 89 patients with follow-up data showed that FSTL1 expression in tumors conferred a favorable postoperative prognosis independently, with a hazard ratio of 0.325 (95% confidence interval: 0.118-0.894). FSTL1 knockdown promoted anchorage independent growth, mobility, and invasion of ccRCC cell lines and promoted cell cycle from G0/G1 phases into S phase; while over-expression of FSTL1 significantly attenuated cell migration ability in ACHN cells. FSTL1 knockdown resulted in decreased expression of E-cadherin and increased expression of N-cadherin in ccRCC cell lines significantly, indicating that FSTL1 may attenuate epithelial to mesenchymal transition in ccRCC. Microarray assay indicated that NF-B and HIF-2 pathways were activated following FSTL1 knockdown in ccRCC cells. Our study indicates that FSTL1 serves as a tumor suppressor in ccRCC, up-regulation of FSTL1 in cancer cells may be a candidate target therapy for advanced ccRCC.
Follistatin-like protein 1 plays a tumor suppressor role in clear-cell renal cell carcinoma.
Specimen part, Cell line
View SamplesRNA localization is a fundamental mechanism for controlling the spatial regulation of protein synthesis within cells, as well as differential cell fates during early development. Localized RNAs are known to control critical aspects of early Xenopus development, but few have been studied in detail. We set out to identify novel transcripts localized to the vegetal cortex of Xenopus oocytes, one of the best-studied examples of RNA localization. We identified over 400 transcripts enriched in the vegetal cortex, compared with whole oocytes. Included were many novel genes, as well as known genes not thought to undergo RNA localization. These data suggest that the role of RNA localization in early development is extensive and will provide a resource for identifying candidate regulatory genes for early developmental processes.
Identification of germ plasm-associated transcripts by microarray analysis of Xenopus vegetal cortex RNA.
Specimen part, Treatment
View SamplesThe sense of hearing depends on the faithful transmission of sound information from the ear to the brain by spiral ganglion (SG) neurons. However, how SG neurons develop the connections and properties that underlie auditory processing is largely unknown.
Developmental profiling of spiral ganglion neurons reveals insights into auditory circuit assembly.
Specimen part
View SamplesWe have analysed the activity of the nuclear exosome during meiosis by deletion of TRF4, which encodes a key component of the exosome targeting complex TRAMP. We find that TRAMP mutants produce high levels of CUTs during meiosis that are undetectable in wild-type cells, showing that the nuclear exosome remains functional for CUT degradation. Lack of TRAMP activity stabilises ~1600 CUTs in meiotic cells, which occupy 40% of the binding capacity of the nuclear cap binding complex (CBC). Overall design: One sample each of Cbc2-associated RNA from wild-type and trf4-deleted cells at 6 hours of meiosis
The nuclear exosome is active and important during budding yeast meiosis.
Subject, Time
View SamplesBackgroud:Epigenetic modifications (especially altered DNA methylation) resulting in altered gene expression may be one reason for development failure or the abnormality of the cloned animals, but the underlying mechanism of the abnormal phenotype in the cloned piglets remains unrevealed. Some cloned piglets in our study showed abnormal phenotypes such as big tongue (longer and thicker), limp, and exomphalos, which is similar to the human BWS syndrome. Here we conducted DNA methylation (DNAm) immunoprecipitation binding high throughput sequencing (MeDIP-seq) and RNA sequencing (RNA-seq) of muscle tissues of cloned piglets to investigate the relationship of abnormal DNAm with gene dysregulation and the unusual phenotypes in cloned piglets. Results:Analysis of the methylomes revealed that abnormal cloned piglets suffered more hypomethylated differentially methylated regions (DMRs) than hypermethylated DMRs compared to the normal cloned piglets. The DNAm level in the CpG Island was higher in the abnormal cloned piglets. Some repetitive elements, such as SINE/tRNA-Glu Satellite/centr also showed significant differences. Besides we detected 1,711 differentially expressed genes (DEGs) between the two groups, of which 243 genes also changed methylation level in the abnormal cloned piglets. The altered DNA methylation mainly affected the low and silent expression genes. We also found some interesting pathways and genes, such as MAPK signalling pathway, hypertrophic cardiomyopathy pathway, TPM3 gene and the imprinted gene PLAGL1, which may played important roles in the abnormal phenotype development. Conclusions;The abnormal cloned piglets showed substantial change both in the DNAm and the gene expression levels. Our data may provide new insights into understanding the molecular mechanisms of the reprogramming of genetic information in cloned animals. Overall design: We dissected the biceps femoris muscle from the abnormal cloned piglets and the normal cloned piglets, and analyzed the difference of MeDIP-seq and RNA-seq between the two groups. This represents the RNA-Seq study only
Transcriptome analysis reveals long intergenic non-coding RNAs involved in skeletal muscle growth and development in pig.
Specimen part, Subject
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