Purpose: to identify differentially regulated pathways and processes in the livers of neonatal Mdr+/- compared to Mdr+/+ mice and correlate these transcriptomics with hepatic lipdomics data Methods: Mdr2+/- mice were mated. There offspring with +/+, +/-, and -/- mdr2 genotypes were kept as litter mates until harvest of livers at 10 days of life. Lobe 1 and 2 were dissected and snap frozen in liquid nitrogen for subsequent RNA isolation and lipid extraction, respectively. RNA-seq libraries were prepared using Illumina TruSeq RNA prep kits and sequenced on the Illumina Hi-Seq 2000. Results: Approximately 20 million reads were mapped to the mm10 mouse genome build using attotations produced by the Ensembl project, which corresponded to 36,400 transcripts. Of these, over 600 transcripts exhibited differential regulation between Mdr+/+ and Mdr+/- samples. Conclusions: Our study supports a pro-inflammatory microenvironment in neonatal, non-infected mdr2+/- compared with wild type mice. Overall design: Hepatic mRNA profiles of Mdr2+/+ and +/- neonatal, BALB/C mice were generated through RNAsequencing.
Hepatic MDR3 expression impacts lipid homeostasis and susceptibility to inflammatory bile duct obstruction in neonates.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Neuronopathic Gaucher disease: dysregulated mRNAs and miRNAs in brain pathogenesis and effects of pharmacologic chaperone treatment in a mouse model.
Specimen part
View SamplesWe found a new spontaneous mutant mouse, laggard, characterized by general weakness in movements and retardation in growth.
Kif14 mutation causes severe brain malformation and hypomyelination.
Specimen part
View SamplesHuman CD8+ T cells are functionally heterogeneous and can be divided into distinct subsets according to CCR7 and CD45RA expression levels. Among the subsets, CCR7-CD45RA+ CD8+ T cells are considered to be terminally differentiated cells and designated as Temra. Temra show attenuated ability to proliferate and produce IFN-gamma in response to TCR stimulation, while Temra show improved function after IL-15 treatment.
IL-15 boosts the function and migration of human terminally differentiated CD8+ T cells by inducing a unique gene signature.
Specimen part, Disease stage
View SamplesComparison of 2 P. s. tritici-inoculated and mock-inoculated genotypes that differ for the Yr39 high-temperature adult-plant resistance phenotype over a time course (12, 24, 48h) ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Tristan Coram. The equivalent experiment is TA11 at PLEXdb.]
Transcriptome analysis of high-temperature adult-plant resistance conditioned by Yr39 during the wheat-Puccinia striiformis f. sp. tritici interaction.
Specimen part, Treatment, Time
View SamplesEstrogen receptor a (ERa) is an important biomarker of breast cancer severity and a common therapeutic target. Recent studies have demonstrated that in addition to its role in promoting proliferation, ERa also protects tumors against metastatic transformation. Current therapeutics antagonize ERa and interfere with both beneficial and detrimental signaling pathways stimulated by ERa. The goal of this study is to uncover the dynamics of coding and non-coding RNA (microRNA) expression in response to estrogen stimulation and identify potential therapeutic targets that more specifically inhibit ERa-stimulated growth and survival pathways without interfering with its protective features. To achieve this, we exposed MCF7 cells (an estrogen receptor positive model cell line for breast cancer) to estrogen and prepared a time course of paired mRNA and miRNA sequencing libraries at ten time points throughout the first 24 hours of the response to estrogen. From these data, we identified three primary expression trends—transient, induced, and repressed—that were each enriched for genes with distinct cellular functions. Integrative analysis of paired mRNA and microRNA temporal expression profiles identified miR-503 as the strongest candidate master regulator of the estrogen response, in part through suppression of ZNF217—an oncogene that is frequently amplified in cancer. We confirmed experimentally that miR-503 directly targets ZNF217 and that over-expression of miR-503 suppresses breast cancer cell proliferation. Overall, these data indicate that miR-503 acts as a potent estrogen-induced tumor suppressor microRNA that opposes cellular proliferation and has promise as a therapeutic for breast cancer. More generally, our work provides a systems-level framework for identifying functional interactions that shape the temporal dynamics of gene expression. Overall design: Quantification of mRNAs in MCF7 cells responding to estrogen following a period of estrogen starvation. Three independent biological replicates (30 samples: 3 replicates x 10 time points) of MCF7 cells were exposed to 10nM Estradiol for 0, 1, 2, 3, 4, 5, 6, 8, 12 , or 24 hours, and total RNA was extracted from the samples. Total RNA was used to generate paired RNA and miRNA sequencing. RNA libraries were prepared using an Illumina TruSeq stranded mRNA library preparation kit.
An integrative transcriptomics approach identifies miR-503 as a candidate master regulator of the estrogen response in MCF-7 breast cancer cells.
No sample metadata fields
View SamplesCachexia is an exacerbating event in many types of cancer that is strongly associated with a poor prognosis. We have identified cytokine, signaling and transcription factors that are required for cachexia in the mouse C26 colon carcinoma model of cancer. C2C12 myotubes treated with conditioned medium from C26 cancer cells induced atrophy and activated a STAT-dependent reporter gene but not reporter genes dependent on SMAD, FOXO, C/EBP, NF-B, or AP-1. Of the gp130 family members IL-11, IL-6, oncostatin M (OSM), and leukemia inhibitory factor (LIF), only OSM and LIF were sufficient to activate the STAT reporter in myotubes. A LIF blocking antibody abolished C26 CM-induced STAT reporter activation STAT3 phosphorylation and myotube atrophy, but blocking antibodies to IL-6 or OSM did not. JAK2 inhibitors also blocked the C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and atrophy in myotubes. LIF at levels found in the C26 CM was sufficient for STAT reporter activation and atrophy in myotubes. In vivo, an increase in serum LIF preceded the increase in IL-6 in mice with C26 tumors. Overexpression of a dominant negative Stat3C-EGFP gene in myotubes and in mouse muscle blocked the atrophy caused by C26 CM or C26 tumors, respectively. Taken together these data support an important role of LIF- JAK2-STAT3 in C26 cachexia and point to a therapeutic approach for at least some types of cancer cachexia.
A Key Role for Leukemia Inhibitory Factor in C26 Cancer Cachexia.
Specimen part, Time
View SamplesWe noticed that ThPOK repression is readily abrogated upon in vitro TCR stimulation of peripheral CD8 T cells. This observation prompted us to investigate a role of ThPOK in the CD8 T cell response to an acute viral infection. We observed that clonal expansion is significantly less in both primary and secondary CD8 T cell responses in the absence of functional ThPOK. To approach this mechanism, we carried out a microarray analysis for comparison of gene expression between ThPOKhd/hd and ThPOKwt/wt P14 memory T cells.
ThPOK derepression is required for robust CD8 T cell responses to viral infection.
No sample metadata fields
View SamplesThe Affymetrix GeneChip Wheat Genome Array currently provides the most comprehensive coverage of the wheat genome for a microarray. In addition to using this resource for transcript expression studies and hybridization-based DNA marker discovery, we endeavored to use the GeneChip to discover the expression of natural antisense transcript (NAT) pairs. By using alternative target preparation schemes, both the sense- and antisense-strand derived transcripts were labeled and hybridized to the Wheat GeneChip. To enable maximum discovery, five different tissue types were selected for assay, and the wheat cultivar Chinese Spring was used considering that most of the GeneChip probe sequences were based on sequencing of this genome. [PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Tristan Coram. The equivalent experiment is TA21 at PLEXdb.]
Large-scale analysis of antisense transcription in wheat using the Affymetrix GeneChip Wheat Genome Array.
No sample metadata fields
View SamplesThe study aimed to identify role of OxyR during growth on different electron acceptors when E. coli are growing anaerobically.
Endogenous protein S-Nitrosylation in E. coli: regulation by OxyR.
No sample metadata fields
View Samples