Microarrays were used to detail the global programme of gene expression comparing wild-type and RNAi knock-down plants of SPT4-1 and SPT4-2
The transcript elongation factor SPT4/SPT5 is involved in auxin-related gene expression in Arabidopsis.
Age, Specimen part
View SamplesNon-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide, yet the pathogenesis of NAFLD is only partially understood. Here, we investigated the role of the gut bacteria in NAFLD by stimulating the gut bacteria via feeding mice the fermentable dietary fiber guar gum and suppressing the gut bacteria via chronic oral administration of antibiotics. Guar gum feeding profoundly altered the gut microbiota composition, in parallel with reduced diet-induced obesity and improved glucose tolerance. Strikingly, despite reducing adipose tissue mass and inflammation, guar gum enhanced hepatic inflammation and fibrosis, concurrent with markedly elevated plasma and hepatic bile acid levels. Consistent with a role of elevated bile acids in the liver phenotype, treatment of mice with taurocholic acid stimulated hepatic inflammation and fibrosis. In contrast to guar gum, chronic oral administration of antibiotics effectively suppressed the gut bacteria, decreased portal secondary bile acid levels, and attenuated hepatic inflammation and fibrosis. Neither guar gum or antibiotics influenced plasma lipopolysaccharide levels. In conclusion, our data indicate a causal link between changes in gut microbiota and hepatic inflammation and fibrosis in a mouse model of NAFLD, possibly via alterations in bile acids.
Modulation of the gut microbiota impacts nonalcoholic fatty liver disease: a potential role for bile acids.
Sex, Specimen part
View SamplesATP6AP2 is an essential accessory component of the vacuolar H+ ATPase (V-ATPase) and has been associated with intellectual disabilities (ID) and Parkinsonism. ATP6AP2 has been implicated in several signaling pathways, but little is known about its role in the nervous system. To decipher its function in behaviour and cognition, we generated and characterized conditional ATP6AP2 Drosophila and mouse models in the nervous system. In Drosophila, knockdown of ATP6AP2 induced defective phototaxis and vacuolisation of photoreceptor neurons and pigment cells when deleted in eyes and alteration of short- and long-term memory when deleted in the mushroom body. In mouse, conditional Atp6ap2 deletion in glutamatergic neurons (Atp6ap2Camk2aCre/0 mice) caused increased spontaneous locomotor activity and altered memory for fear. Both Drosophila ATP6AP2 knockdown and Atp6ap2Camk2aCre/0 mice presented with presynaptic transmission defect, abnormal number and morphology of synapses, and alteration of axonal transport in fly. In addition, Atp6ap2Camk2aCre/0 mice showed autophagy defect leading to axonal and neuronal degeneration in the cortex and the hippocampus. Surprisingly, myelinisation of axons was affected in our mutant mice. In accordance with the identified phenotypes across species, genome-wide transcriptome profiling of Atp6ap2Camk2aCre/0 mouse hippocampi revealed dysregulated genes involved in myelination, action potential, membrane bound vesicles and adult behaviour. In summary, disruption of ATP6AP2 in mouse and fly leads to cognitive impairment and neurodegeneration, mimicking aspects of the neuropathology associated with ATP6AP2 mutations in humans. Our results identify ATP6AP2 as an essential gene for the nervous system. Overall design: 4 samples, 2 wt and 2 Atp6ap2Camk2aCre/0
Conditional depletion of intellectual disability and Parkinsonism candidate gene ATP6AP2 in fly and mouse induces cognitive impairment and neurodegeneration.
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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
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