The goal was to study the effects of lead exposure on gene expression and identify the lead-responsive genes. After detecting 1,536 cis-eQTLs (FDR = 10%) and 952 trans-eQTLs, we focused our analysis on Pb-sensitive “trans-eQTL hotspots”. Overall design: 158 randomly selected Drosophila Synthetic Population Resource (A2) samples (control 79 samples and Pb-treated) without replicates
Identification of Splicing Quantitative Trait Loci (sQTL) in <i>Drosophila melanogaster</i> with Developmental Lead (Pb<sup>2+</sup>) Exposure.
Cell line, Subject
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Dicer deficiency reveals microRNAs predicted to control gene expression in the developing adrenal cortex.
Specimen part
View SamplesMicroRNAs (miRNAs) are small, endogenous, non-protein coding RNAs that are an important means of post-transcriptional gene regulation. Deletion of Dicer, a key miRNA processing enzyme, is embryonic lethal in mice, and tissue-specific Dicer deletion results in developmental defects. Using a conditional knockout model, we generated mice lacking Dicer in the adrenal cortex. These Dicer knockout (KO) mice exhibited perinatal mortality and failure of the adrenal cortex during late gestation between embryonic day 16.5 (E16.5) and E18.5. Further study of Dicer KO adrenals demonstrated a significant loss of Sf1 expressing cortical cells that was histologically evident as early as E16.5 coincident with an increase in p21 and cleaved-caspase 3 staining in the cortex. However, peripheral cortical proliferation persisted in KO adrenals as assessed by anti-PCNA staining. To further characterize the embryonic adrenals from Dicer KO mice, we performed microarray analyses for both gene expression and miRNA on purified RNA isolated from control and KO adrenals of E15.5 and E16.5 embryos. Consistent with the absence of Dicer and the associated loss of miRNA-mediated mRNA degradation, we observed an up-regulation of a small subset of adrenal transcripts in Dicer KO mice, most notably the transcripts coded by the genes Nr6a1 and Acvr1c. Indeed, several miRNAs, including let-7, miR-34c, and miR-21 that are predicted to target these genes for degradation, were also markedly down-regulated in Dicer KO adrenals. Together these data suggest a role for miRNA mediated regulation of a subset of genes that are essential for normal adrenal growth and homeostasis.
Dicer deficiency reveals microRNAs predicted to control gene expression in the developing adrenal cortex.
Specimen part
View SamplesBackground: The muscularis externa (ME) of the adult intestine consists of two layers of visceral smooth muscle (VISM), the inner circular muscle (ICM) and outer longitudinal muscle (OLM), that form sequentially beginning at embryonic day (E) 13 and E15 in the developing mouse. Coordinated contraction of these two layers facilitates the movement of food down the digestive tract. Though abnormal ME function or development has been linked to pseudoobstruction and irritable bowel syndrome, little is known about the molecular character of the smooth muscle that comprises this tissue. We performed transcriptome analysis to identify genes that are enriched in intestinal mesenchyme tissue at E14.5, when the inner circular muscle (ICM) is well established. Results: Expression patterns of enriched mesenchyme genes were examined in publically available in situ databases, revealing over one hundred genes that are expressed in the ICM. Examination of the promoter regions for these genes revealed enrichment for cJUN transcription factor binding sites and cJUN itself was also enriched in ICM. A cJUN ChIP-seq at E14.5 showed that cJUN regulatory regions contained characteristics of muscle enhancers. Overall design: E14.5 mouse intestines were harvested and grown for 24 hours in a transwell culture with or without Cyclopamine treatment. Separated epithelial and mesenchyme tissue populations or whole intestines were submitted for sequencing. Three replicates for each condition were collected.
Transcriptome of the inner circular smooth muscle of the developing mouse intestine: Evidence for regulation of visceral smooth muscle genes by the hedgehog target gene, cJun.
Specimen part, Cell line, Subject
View SamplesBackgropund:In a major paradigm shift in the last decade, the knowledge about a whole class of non-coding RNAs known as miRNAs has emerged, which have proved these to be important regulators of a wide range of cellular processes by the way of modulation of gene expression. It is reported that some of these miRNAs are modified by addition or deletion of nucleotides at their ends, after biogenesis. However, the biogenesis and functions of these modifications are not well studied in eukaryotes, especially in plants. In this study, we examined the miRNA modifications in different tissues of the various plants, namely rice, tomato and Arabidopsis and identified some common features of such modifications. Results:We have analyzed different aspects of miRNA modifications in plants. To achieve this end, we developed a PERL script to find the modifications in the sequences using small RNA deep sequencing data. The modification occurs in both mature and passenger (star) strands, as well as at both the 5'' and 3'' ends of miRNAs. Interestingly, we found a position-specific nucleotide biased modification, as evident by increased number of modification at the 5'' end with the presence of Cytosine (nucleotide ''C'') at the 3’end of the miRNA sequence. The level of modifications is not strictly dependent on the abundance of miRNA. Our study showed that the modification events are independent of plant species, tissue and physiological conditions. Our analysis also indicates that the RNAi enzyme, namely, the RNA dependent RNA polymerase 6 (RDR6) may not have any role in Arabidopsis miRNA modifications. Some of these modified miRNAs are bound to AGO1, suggesting their possible roles in biological processes. Conclusions:This is a first report that reveals that 5'' nucleotide additions are preferred for mature miRNA sequences with 3’ terminal ‘C’ nucleotide. Our analysis also indicates that the miRNAs modifications involving addition of nucleotides to the 5’ or 3’ end are independent of RDR6 activity and are not restricted by plant species, physiological conditions and tissue types. The results also indicate that such modifications might be important for biological processes. Overall design: small RNA profiles of wild type and RDR6 (-) of Arabidopsis plants were generated using deep sequencing data.
3' and 5' microRNA-end post-biogenesis modifications in plant transcriptomes: Evidences from small RNA next generation sequencing data analysis.
Subject
View SamplesWe have performed a genome-wide analysis of common genetic variation controlling differential expression of transcript isoforms in the CEU HapMap population using a comprehensive exon tiling microarray covering 17,897 genes. We detected 324 genes with significant associations between flanking SNPs and transcript levels. Of these, 39% reflected changes in whole gene expression and 55% reflected transcript isoform changes such as splicing variants (exon skipping, alternate splice site usage, intron retention), differential 5 UTR (initiation of transcription) usage, and differential 3 UTR (alternative polyadenylation) usage.
Genome-wide analysis of transcript isoform variation in humans.
Sex
View SamplesRNA sequencing was performed to determine the uniqueness of splenic follicular IgD low B cells compared to splenic follicular IgD high and marginal zone B cells. Overall design: Splenic follicular IgD low and IgD high , and MZ B cells were sorted by FACS from naïve 8-10 weeks old mice. Total RNA was isolated from the sorted cells using RNAqueous® -4PCR kit and RNA sequencing was performed. Splenocytes from five mice were pooled for each sorting. Three independent sorting was performed for each B cell subset.
Mature IgD<sup>low/-</sup> B cells maintain tolerance by promoting regulatory T cell homeostasis.
Specimen part, Cell line, Subject
View SamplesOsteoblasts are key players in bone remodeling. The accessibility of human primary osteoblast-like cells (HOb) from bone explants render them a lucrative model for studying molecular physiology of bone turnover, discovery of novel anabolic therapeutics and mesenchymal cell biology in general. Relatively little is known about resting and dynamic expression profiles of HObs and no studies have been conducted to date to systematically assess the osteoblast transcriptome. The aim of this study was to characterize HObs and investigate signaling cascades and gene networks using genomewide expression profiling in resting and Bone Morphogenic Protein (BMP)-2 and Dexamethasone induced cells.
Systematic assessment of the human osteoblast transcriptome in resting and induced primary cells.
No sample metadata fields
View SamplesHepatocellular carcinoma (HCC) is the fifth most-common cancer worldwide causing nearly 600,000 deaths esch year. Approximately 80% of HCC develops on the background of cirrhosis.It is necessary to identify novel genes involved in HCC to implement new diagnostic and treatment options. However, the molecular pathogenesis of HCC largely remains unsolved. Only a few genetic alterations, namely those affecting p53, -catenin and p16INK4a have been implicated at moderate frequencies of these cancers. Early detection of HCC with appropriate treatment can decrease tumor-related deaths
Genome-wide transcriptional reorganization associated with senescence-to-immortality switch during human hepatocellular carcinogenesis.
Specimen part
View SamplesCellular senescence is a tumor suppressor mechanism, and immortalization facilitates neoplastic transformation. Both mechanisms may be highly relevant to hepatocellular carcinoma (HCC) development and its molecular heterogeneity. Cellular senescence appears to play a major role in liver diseases. Chronic liver diseases are associated with progressive telomere shortening leading senescence that is observed highly in cirrhosis, but also in some HCC. We previously described the generation of immortal and senescence-programmed clones from HCC-derived Huh7 cell line.
Genome-wide transcriptional reorganization associated with senescence-to-immortality switch during human hepatocellular carcinogenesis.
Sex, Specimen part
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