Microcystin-LR (MC-LR), the most toxic member of microcystin family, inhibits protein phosphatase PP2A, triggers oxidative stress and induces hepatotoxicity. Gene expression profiling of MC-LR treated larvae using DNA microarray analysis revealed effects in the retinal visual cycle and pigmentation synthesis pathways that have not been previously associated with MC-LR. Liver-related genes were also differentially expressed. The microarray data were confirmed by quantitative real-time PCR. Our findings provide new evidence that microcystin-LR exposure of zebrafish larvae modulates the retinal visual cycle and pigmentation synthesis pathways and ultimately alter larval zebrafish behavior
Transcriptional and Behavioral Responses of Zebrafish Larvae to Microcystin-LR Exposure.
Specimen part
View SamplesWe have characterised the zebrafish ortholog, setb, and investigated its role in embryogenesis. Phylogenetic analysis showed that zebrafish Setb has an amino acid sequence identity of approximately 96% with the mammalian orthologs. Whole mount immunofluorescence analysis revealed that Setb is expressed mainly in the eye, the lateral line neuromasts and the olfactory pit. Knockdown of setb using antisense morpholino oligonucleotides resulted in increased apoptosis, reduced cell proliferation and severe morphological defects. The morphant phenotypes were partially rescued when setb MO1 was co-injected with human set mRNA. In vivo labelling of hair cells in the lateral line of setb morphants with the vital fluorescent dye FM1-43 showed a significant decreased number of functional neuromasts. Gene expression analysis of setb morphants, employing DNA microarrays revealed a role of Setb in neurogenesis and the mechanosensory lateral line system.
The zebrafish homologs of SET/I2PP2A oncoprotein: expression patterns and insights into their physiological roles during development.
Treatment
View SamplesBoth cigarette smoking and obesity have been implicated in increased risk of clear cell renal cell carcinoma (ccRCC); however, there are limited data regarding the molecular mechanisms that underlie these associations. We used a multi-stage design to identify and validate specific molecular targets that are associated with smoking or obesity-related ccRCC.
ANKS1B is a smoking-related molecular alteration in clear cell renal cell carcinoma.
Specimen part, Subject
View SamplesUsing zebrafish tet2-/-;tet3-/- mutants, we identify functions for Tet enzymes and 5-hydroxymethylcytosine (5hmC) in regulating gene expression and cell type-specific differentiation during retinal development. Overall design: RNAseq from tet2-/-;tet3-/- mutant and sibling embryonic eye tissues dissected at 72hpf and 36hpf.
Tet-mediated DNA hydroxymethylation regulates retinal neurogenesis by modulating cell-extrinsic signaling pathways.
No sample metadata fields
View SamplesIt is unknown if gene expression profiles from primary RCC tumors differ from patient-matched metastatic tumors. Thus, we sought to identify differentially expressed genes between patient-matched primary and metastatic RCC tumors in order to understand the molecular mechanisms underlying the development of RCC metastases.
Differential gene expression profiling of matched primary renal cell carcinoma and metastases reveals upregulation of extracellular matrix genes.
Specimen part, Subject
View SamplesAdvantages of RNA-Seq over array based platforms are quantitative gene expression and discovery of expressed single nucleotide variants (eSNVs) and fusion transcripts from a single platform, but the sensitivity for each of these characteristics is unknown. We measured gene expression in a set of manually degraded RNAs, nine pairs of matched fresh-frozen, and FFPE RNA isolated from breast tumor with the hybridization based, NanoString nCounter, (226 gene panel) and with whole transcriptome RNA-Seq using RiboZeroGold ScriptSeq V2 library preparation kits. We performed correlation analyses of gene expression between samples and across platforms. We then specifically assessed whole transcriptome expression of lincRNA and discovery of eSNVs and fusion transcripts in the FFPE RNA-Seq data. For gene expression in the manually degraded samples, we observed Pearson correlation of >0.94 and >0.80 with NanoString and ScriptSeq protocols respectively. Gene expression data for matched fresh-frozen and FFPE samples yielded mean Pearson correlations of 0.874 and 0.783 for NanoString (226 genes) and ScriptSeq whole transcriptome protocols respectively. Specifically for lincRNAs, we observed superb Pearson correlation (0.988) between matched fresh-frozen and FFPE pairs. FFPE samples across NanoString and RNA-Seq platforms gave a mean Pearson correlation of 0.838. In FFPE libraries, we detected 53.4% of high confidence SNVs and 24% of high confidence fusion transcripts. Sensitivity of fusion transcript detection was not overcome by an increase in depth of sequencing up to 3-fold (increase from ~56 to ~159 million reads). Both NanoString and ScriptSeq RNA-Seq technologies yield reliable gene expression data for degraded and FFPE material. The high degree of correlation between NanoString and RNA-Seq platforms suggests discovery based whole transciptome studies from FFPE material will produce reliable expression data. The RiboZeroGold ScriptSeq protocol performed particularly well for lincRNA expression from FFPE libraries but detection of eSNV and fusion transcripts was less sensitive. Overall design: We performed RNASeq on RNA from nine matched pairs of fresh-frozen and FFPE tissues from breast cancer patients. The goal was to test the RiboZeroGold ScriptSeq complete low input library preparation kit for degraded RNA samples.
Gene expression, single nucleotide variant and fusion transcript discovery in archival material from breast tumors.
No sample metadata fields
View SamplesIn mammals, expansion of adipose tissue mass induces accumulation of adipose tissue macrophages (ATMs). We isolated CD11c- (FB) and CD11c+ (FBC) perigonadal ATMs from SVCs of lean (C57BL/6J Lep +/+) and obese leptin-deficient (C57BL/6J Lep ob/ob) mice.
Obesity activates a program of lysosomal-dependent lipid metabolism in adipose tissue macrophages independently of classic activation.
Specimen part
View SamplesThe dermal papilla plays a key role in the regulation of the hair biology. Accordingly, human dermal papilla cells (hDPCs) may be functionally impaired in female pattern hair loss. A previous observation that beta-estradiol (E2) increased hair density in ovariectomized mice suggested that E2 might modulate the biological properties of hDPCs. Therefore, to further explore the effect of E2 on hDPCs, a global gene expression analysis was conducted.
Reversal of the hair loss phenotype by modulating the estradiol-ANGPT2 axis in the mouse model of female pattern hair loss.
Sex, Age, Specimen part, Treatment, Race
View SamplesThe basic defect of IgA nephropathy (IgAN) lies within peripheral blood mononuclear cells rather than local kidney abnormalities. Previously we showed an altered gene expression in monocytes compared to B and T cells isolated from IgAN patients (Kidney Int, 2010), thus our aim here was to study this subset more closely at genome-wide level.
Altered monocyte expression and expansion of non-classical monocyte subset in IgA nephropathy patients.
Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Histone Methyltransferase G9a Is Required for Cardiomyocyte Homeostasis and Hypertrophy.
Treatment
View Samples