Detailed analysis of genome-wide transcriptome profiling in rice root is reported here, following Cr-plant interaction. Such studies are important for the identification of genes responsible for tolerance, accumulation and defense response in plants with respect to Cr stress. Rice root metabolome analysis was also carried out to relate differential transcriptome data to biological processes affected by Cr (VI) stress in rice.
Transcriptomic and metabolomic shifts in rice roots in response to Cr (VI) stress.
Age, Specimen part, TreatmentView Samples
Background: We hypothesize that important genomic differences between breast cancer subtypes occur early in carcinogenesis. Therefore, gene expression might distinguish histologically normal breast epithelium (NlEpi) from breasts containing estrogen receptor positive (ER+) compared with estrogen receptor negative (ER-) cancers.
Gene expression profiles of estrogen receptor-positive and estrogen receptor-negative breast cancers are detectable in histologically normal breast epithelium.
Specimen part, Disease, Disease stageView Samples
Cerebral malaria is a severe multifactorial condition associated with the interaction of high numbers of infected erythrocytes to human brain endothelium without invasion into the brain. The result is coma and seizures with death in more than 20% of cases. Because the brain endothelium is at the interface of these processes, we investigated the global gene responses of human brain endothelium after the interaction with Plasmodium falciparuminfected erythrocytes with either high- or low-binding phenotypes. The most significantly up-regulated transcripts were found in gene ontology groups comprising the immune response, apoptosis and antiapoptosis, inflammatory response, cell-cell signaling, and signal transduction and nuclear factor B (NF-B) activation cascade. The proinflammatory NF-B pathway was central to the regulation of the P falciparummodulated endothelium transcriptome. The proinflammatory molecules, for example, CCL20, CXCL1, CXCL2, IL-6, and IL-8, were increased more than 100-fold, suggesting an important role of blood-brain barrier (BBB) endothelium in the innate defense during P falciparuminfected erythrocyte (Pf-IRBC) sequestration. However, some of these diffusible molecules could have reversible effects on brain tissue and thus on neurologic function. The inflammatory pathways were validated by direct measurement of proteins in brain endothelial supernatants. This study delineates the strong inflammatory component of human brain endothelium contributing to cerebral malaria.
Plasmodium falciparum-infected erythrocytes induce NF-kappaB regulated inflammatory pathways in human cerebral endothelium.
No sample metadata fieldsView Samples
P. falciparum NF54 proliferates under micro-aerophilic conditions in an environment of 3% O2, 4% CO2, 93% N2. This strain was gradually adapted to proliferate under standard tissue culture conditions of 5% CO2/95% air (~19% O2) to generate P. falciparum HOX. We compared global gene expression profiles of the two strains to identify differences, if any.
Model system to define pharmacokinetic requirements for antimalarial drug efficacy.
No sample metadata fieldsView Samples
DAZAP1 was depleted in culterd HEK 293T cells using shRNA and the resulting poly A RNA were isolated c-DNA library constructed and paired end sequenced on illumina Hi-seq 2000 platform the data was compared to a control shRNA depleted cell Overall design: Gene expression and splicing switches upon DAZAP1 knockdown
The splicing activator DAZAP1 integrates splicing control into MEK/Erk-regulated cell proliferation and migration.
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Malat1 is an abundant long noncoding RNA that localizes to nuclear bodies known as nuclear speckles, which contain a distinct set of pre-mRNA processing factors. Previous in vitro studies have demonstrated that Malat1 interacts with pre-mRNA splicing factors, including the serine- and arginine-rich (SR) family of proteins, and regulates a variety of biological processes, including cancer cell migration, synapse formation, cell cycle progression, and responses to serum stimulation. To address the physiological function of Malat1 in a living organism, we generated Malat1-KO (KO) mice using homologous recombination. Unexpectedly, the Malat1-KO mice were viable and fertile, showing no apparent phenotypes. Nuclear speckle markers were also correctly localized in cells that lacked Malat1. However, the cellular levels of another long noncoding RNA, Neat1, which is an architectural component of nuclear bodies known as paraspeckles, were downregulated in a particular set of tissues and cells lacking Malat1.
Malat1 is not an essential component of nuclear speckles in mice.
Specimen partView Samples
This study takes on the problem of bridging transcriptional data to neuronal phenotype and function by using publicly available datasets characterizing distinct neuronal populations based on gene expression, electrophysiology and morphology. In addition, a non-published PatchSeq dataset of Pvalb-cre positive cells in CA1 was used, which is the dataset submitted here. Taken together, these datasets were used to identify cross-cell type correlations between these data modalities. Detected correlations were classified as “class-driven” if they could be explained by differences between excitatory and inhibitory cell classes, or “non-class driven” if they could be explained by gradient like phenotypic differences within cell classes. Some genes whose relationships to electrophysiological or morphological properties were found to to be specific to either excitatory or inhibitory cell types. The Patch Seq data specifically allowed simultaneous single-cell characterization of gene expression and electrophysiology, showing that the gene-property correlations observed across cell types were further predictive of within-cell type heterogeneity. Overall design: Patchseq data was collected from single cells of the mouse hippocampus CA1 in order to investigate correlations between gene expression patterns and electrophysiological properties of various interneuron cell classes 19 individual cells Re-analysis details included in supplementary file readme.txt.
Transcriptomic correlates of electrophysiological and morphological diversity within and across excitatory and inhibitory neuron classes.
Age, Specimen part, SubjectView Samples
BACKGROUND: We characterized the whole transcriptome of circulating tumor cells (CTCs) in Stage II-III breast cancer to evaluate correlations with primary tumor biology. METHODS: CTCs were isolated from peripheral blood (PB) via immunomagnetic enrichment followed by fluorescence-activated cell sorting (IE-FACS). CTCs, PB and fresh tumors were profiled with RNA Seq. Formalin-fixed, paraffin-embedded (FFPE) tumors were subjected to RNA Seq and NanoString PAM50 assays with Risk of Recurrence (ROR) scores. RESULTS: CTCs were detected in 29/33 (88%) of patients. We selected 21 cases to attempt RNA Seq (median number of CTCs=9). 16 CTC samples yielded results that passed quality control metrics. These samples had a median of 4,311,255 uniquely mapped reads, less than PB or tumors. Intrinsic subtype predicted by comparing estrogen receptor (ER), progesterone receptor (PR) and HER2 versus PAM50 for FFPE tumors was 85% concordant. However, CTC RNA Seq subtype assessed by the PAM50 classification genes was highly discordant both with the subtype predicted by ER/PR/HER2 as well as by tumor PAM50. Two patients died of metastatic disease - both had high ROR scores and high CTC counts. We identified significant genes, canonical pathways, upstream regulators and molecular interaction networks comparing CTCs by various clinical factors. We identified a 75-gene signature with highest expression in CTCs and tumors taken together that was prognostic in The Cancer Genome Atlas and METABRIC datasets. CONCLUSION: It is feasible to use RNA Seq of CTCs in non-metastatic patients to discover novel tumor biology characteristics. Overall design: 6 peripheral blood samples from healthy individuals (negative controls) were compared to circulating tumor cells from n=16 patients, with comparison to the primary tumors available for n=12 of these patients
RNA-Seq of Circulating Tumor Cells in Stage II-III Breast Cancer.
Disease, Disease stage, SubjectView Samples
Leishmania major infected human dendritic cells (DCs) exhibit a marked induction of IL-12 ultimately promoting a robust Th1-mediated response associated with parasite killing and protective immunity. In this study, we utilized Affymetrix Genechips to globally assess the host cell genes and pathways associated with L. major infection during early infection (2, 4, 8, and 24 hrs) in human myeloid-derived DCs. Bioinformatic analyses of the hybridized microarray chips identified 728 genes, represented by 848 unique probe sets, which, when compared to uninfected samples were observed to be significantly differentially expressed by one-way ANOVA. Altogether, the data provide a genome-wide perspective on the transcriptional influences Leishmania species exert within human DCs during early infection, and provides a platform for further investigations toward functionally characterizing candidate genes of importance to the IL-12 based immune response to infections.
Human dendritic cells exhibit a pronounced type I IFN signature following Leishmania major infection that is required for IL-12 induction.
Specimen part, TimeView Samples