Goal: To define the digital transcriptome of three breast cancer subtypes (TNBC, Non-TNBC, and HER2-positive) using RNA-sequencing technology. To elucidate differentially expressed known and novel transcripts, alternatively spliced genes and differential isoforms and lastly expressed variants in our dataset. Method: Dr. Suzanne Fuqua (Baylor College of Medicine) provided the human breast cancer tissue RNA samples. All of the human samples were used in accordance with the IRB procedures of Baylor College of Medicine. The breast tumour types, TNBC, Non-TNBC and HER2-positive, were classified on the basis of immunohistochemical and RT-qPCR classification. Results: Comparative transcriptomic analyses elucidated differentially expressed transcripts between the three breast cancer groups, identifying several new modulators of breast cancer. We discovered subtype specific differentially spliced genes and splice isoforms not previously recognized in human transcriptome. Further, we showed that exon skip and intron retention are predominant splice events in breast cancer. In addition, we found that differential expression of primary transcripts and promoter switching are significantly deregulated in breast cancer compared to normal breast. We also report novel expressed variants, allelic prevalence and abundance, and coexpression with other variation, and splicing signatures. Additionally we describe novel SNPs and INDELs in cancer relevant genes with no prior reported association of point mutations with cancer Overall design: mRNA profiles of 17 breast tumor samples of three different subtypes (TNBC, non-TNBC and HER2-positive) and normal human breast organoids (epithelium) samples (NBS) were sequenced using Illumina HiSeq.
Novel insights into breast cancer genetic variance through RNA sequencing.
No sample metadata fields
View SamplesAuxin-dependent transcript abundance was assayed by transferring 6 day old Arabidopsis grown on a a nylon mesh to IAA-containing or control media
A kinetic analysis of the auxin transcriptome reveals cell wall remodeling proteins that modulate lateral root development in Arabidopsis.
Specimen part
View SamplesIn this study, we aim to identify candidate biomarkers which may be useful as surrogate indicators of toxicity for pre-clinical development of panPPAR-agonist drug candidates. Gene expression microarray, histopathology and clinical chemistry data were generated from liver, heart, kidney and skeletal muscles of three groups of mice administered with three different dosages of an experimental pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist, PPM-201, for 14 days. The histopathology and clinical chemistry data were compared with the gene expression analysis and candidate biomarker genes were identified.
Simultaneous non-negative matrix factorization for multiple large scale gene expression datasets in toxicology.
Specimen part, Treatment
View SamplesA major contributor to cancer mortality is recurrence and subsequent metastatic transformation following therapeutic intervention. In order to develop new treatment modalities or improve the efficacy of current ones it is important to understand the molecular mechanisms that promote therapy-resistance to cancer cells. One pathway that has been demonstrated to therapy resistance is autophagy, a self-digestive process that can eliminate unnecessary or damaged organelles to protect cancer cells from necrosis. Effective targeting of this pathway could lead to the development of new therapies. In our studies, we found that the VEGF-C/NRP-2 axis is involved in the activation of autophagy, which is essential for the survival of cancer cells following chemotherapy treatment. Furthermore, we identified two VEGF-C/NRP-2-regulated genes, LAMP-2 and WDFY-1 that have previously been suggested to participate in autophagy and vesicular trafficking. The upregulation of WDFY-1 upon depleted level of VEGF-C contributed to cytotoxic drug-mediated cell death. Altogether, these data suggest a link between VEGF-C/neuropilin-2 axis and cancer cell survival despite the presence of chemotherapy-induced stress.
Autophagy control by the VEGF-C/NRP-2 axis in cancer and its implication for treatment resistance.
Cell line
View SamplesThe trade-off between growth and immunity is crucial for survival in plants. An antagonistic interaction has been observed between the growth-promoting hormone brassinosteroid and pathogen associated molecular pattern (PAMP) signals, which induce immunity but inhibit growth, however the underlying molecular mechanism has remained unclear. The PRE-IBH1-HBI1 triple helix-loop-helix/basic helix-loop-helix (HLH/bHLH) cascade has been shown to mediate growth responses to several hormonal and environmental signals, but its downstream targets and role in immunity remain unknown. Here, we performed genome-wide analyses of HBI1 target genes in Arabidopsis. The results show that HBI1 regulates a set of genes that largely overlaps with targets of PIFs, but displays both similar and unique transcriptional activities compared to PIFs, supporting a role in fine-tuning the network through cooperation and antagonism with other DNA-binding factors of the network. Furthermore, HBI1 also negatively regulates a subset of defense response genes. Two PAMPs, flagellin and elongation factor, repressed HBI1 expression, whereas overexpression of HBI1 reduced the PAMP-induced growth inhibition, defense gene expression, reactive oxygen species (ROS) production, and flg22-induced resistance to Pseudomonas syringae pathovar tomato DC3000. These data indicate that HBI1 is a node for crosstalk between hormone and immune pathways. This study demonstrates that the PRE-IBH1-HBI1 module integrates hormone and pathogen signals, and thus plays a central role in the balance between growth and immunity in plants. Overall design: Compare the transcriptome of HBI1-Ox and wild type.
The bHLH transcription factor HBI1 mediates the trade-off between growth and pathogen-associated molecular pattern-triggered immunity in Arabidopsis.
Subject
View SamplesWe used microarrays to analyze gene expression changes in liver after treatment of rats with two compounds from drug development (R1, R2) to identify potential effects related to hepatotoxicity.
Gene expression-based in vivo and in vitro prediction of liver toxicity allows compound selection at an early stage of drug development.
Sex, Specimen part, Treatment
View SamplesTMPRSS6 is a type II transmembrane serine protease and is revealed by our work to be part of a low-iron sensing pathway. When animal gets iron deficient, TMPRSS6 is required to shut off hepcidin gene, so as to allow iron to be uptaken from GI tract. The mutant mouse, which was generated by ENU mutagenesis, has developed microcytic anemia. The phenotype is caused by a splicing error in Tmprss6 gene. However, the mechanism of TMPRSS6 effect remains elusive. To gain further insight into the molecular components of the TMPRSS6 signaling pathway, we overexpressed either TMPRSS6 or its mutant version of protein in human liver carcinoma cell line HepG2 cells, and compared the transcription status betweem these two treatments.
The serine protease TMPRSS6 is required to sense iron deficiency.
No sample metadata fields
View SamplesThe goal of this study is to compare gene expression levels in uhrf1 mutants with global DNA hypomethylation to WT siblings Overall design: 10 whole embryos were pooled per sample of either 5 dpf old uhrf1 mutants or phenotypically WT siblings and RNA was extracted. Libraries were prepared according to Illumina Truseq RNA sample prep kit, version 2, followed by Ribo-Zero Gold treatment
Loss of DNA methylation in zebrafish embryos activates retrotransposons to trigger antiviral signaling.
No sample metadata fields
View SamplesThe purpose of this study was to investigate whether paternal high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa to alter metabolism in the F1 and F2 generation offspring
High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring.
Sex, Specimen part
View SamplesThe polarization of macrophages into an anti-inflammatory or regulatory phenotype plays an important role in resolving inflammation. PGE2 regulates macrophage polarization via a PKA dependent pathway. PKA phosphorylates SIKs, inhibiting their ability to phosphorylate CRTC3 in cells. This in turn allows CRTC3 to translocate to the nucleus where it acts as a co-activator with the transcription factor CREB to induce IL-10 transcription. In line with this we find that either genetic or pharmacological inhibition of SIKs mimics the effect of PGE2 on IL-10 production.
PGE(2) induces macrophage IL-10 production and a regulatory-like phenotype via a protein kinase A-SIK-CRTC3 pathway.
Specimen part
View Samples