Plasmacytoid dendritic cells (pDC) are the major source of type I and type III interferons (IFN-I/III) during viral infections, in response to triggering of endosomal Toll Like Receptors (TLRs) 7 or 9 by viral single-stranded RNA or unmethylated CpG DNA, respectively. Interestingly, this function is restricted to a minor fraction of pDC (Zucchini et al. Int. Immunol. 2008). In this project, we aimed at identifying the molecular pathways involved in inducing IFN-I/III production in this minor faction of pDC during in vivo infection by the mouse cytomegalovirus (MCMV). To achive this goal, we infected with MCMV Ifnb1Eyfp mice, in which IFN-producing pDC can be detected by YFP expression (Scheu et al. PNAS 2008). Thanks to this model, we were able to sort three distinct subsets of pDC: CD86-YFP- (not activated, non IFN-producing), CD86+YFP- (activated, non IFN-producing) and CD86+YFP+ (activated, IFN-producing) and to perform microarray analysis. This allowed us to select genes differentially expressed among these three subsets and to mine these data in order to identify the related signaling pathways.
The activation trajectory of plasmacytoid dendritic cells in vivo during a viral infection.
Specimen part, Treatment
View SamplesGene expression microarray profile for human embryonic kidney cells (HEK293T, CRL-11268) under untreated conditions.
The identification of protein kinase C iota as a regulator of the Mammalian heat shock response using functional genomic screens.
Specimen part, Cell line
View SamplesSox3 has been shown to be expressed within neural progenitors of the developing mouse central nervous system. However, identification of Sox3 targets within neural progenitors has remained elusive.
Dbx1 is a direct target of SOX3 in the spinal cord.
Specimen part, Cell line
View SamplesWe profile gene expression changes in two mutant strains lacking the D. melanogaster HP1 homolog HP1B at the third instar larval stage. Compared to the yw control strain, several hundred genes are deregulated, with metabolic genes being over-represented among the deregulated gene set. Overall design: Examination of gene expression in two genotypes
HP1B is a euchromatic Drosophila HP1 homolog with links to metabolism.
Specimen part, Cell line, Subject
View SamplesGene expression profiling is a promising diagnostic and prognostic tool. Expression profiles are snap-shots of mRNA levels at time of extraction and they have been shown to be affected by tissue handling during sample collection. The effect of cold (room temperature) ischemia in the time interval between surgical removal of the specimen and freezing has been described in a number of studies. However, not much is known about the effect of warm (body temperature) ischemia during surgery.
Differential effect of surgical manipulation on gene expression in normal breast tissue and breast tumor tissue.
Sex, Specimen part, Disease, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Profiling of the transcriptional response to all-trans retinoic acid in breast cancer cells reveals RARE-independent mechanisms of gene expression.
Cell line
View SamplesThe primary goal of toxicology and safety testing is to identify agents that have the potential to cause adverse effects in humans. Unfortunately, many of these tests have not changed significantly in the past 30 years and most are inefficient, costly, and rely heavily on the use of animals. The rodent cancer bioassay is one of these safety tests and was originally established as a screen to identify potential carcinogens that would be further analyzed in human epidemiological studies. Today, the rodent cancer bioassay has evolved into the primary means to determine the carcinogenic potential of a chemical and generate quantitative information on dose-response behavior in chemical risk assessments. Due to the resource-intensive nature of these studies, each bioassay costs $2 to $4 million and takes over three years to complete. Over the past 30 years, only 1,468 chemicals have been tested in a rodent cancer bioassay. By comparison, approximately 9,000 chemicals are used by industry in quantities greater than 10,000 lbs and nearly 90,000 chemicals have been inventoried by the U.S. Environmental Protection Agency as part of the Toxic Substances Control Act. Given the disparity between the number of chemicals tested in a rodent cancer bioassay and the number of chemicals used by industry, a more efficient and economical system of identifying chemical carcinogens needs to be developed.
Application of genomic biomarkers to predict increased lung tumor incidence in 2-year rodent cancer bioassays.
Sex, Age, Subject
View SamplesRetinoids, derivatives of vitamin A, are key physiological molecules with regulatory effects on cell differentiation, proliferation and apoptosis. As a result, they are of interest for cancer therapy. Specifically, models of breast cancer have varied responses to manipulations of the retinoid signaling cascade. This study characterizes the transcriptional response of MDA-MB-231 and MDA-MB-468 breast cancer cells to retinaldehyde dehydrogenase 1A3 (ALDH1A3) and to all-trans retinoic acid (atRA). We demonstrate limited overlap between ALDH1A3-induced gene expression and atRA-induced gene expression in both cell lines, suggesting that the function of ALDH1A3 in breast cancer progression extends beyond its role as a retinaldehyde dehydrogenase. Our data reveals divergent transcriptional responses to atRA, which are largely independent of genomic retinoic acid response elements (RAREs) and consistent with the opposing responses of MDA-MB-231 and MDA-MB-468 to in vivo atRA treatment. We identify transcription factors associated with each gene set. Manipulation of one of the transcription factors (i.e. interferon regulatory factor 1; IRF1) demonstrates that it is the level of atRA-inducible and epigenetically regulated transcription factors that determine expression of target genes (e.g. CTSS, cathepsin S). This study provides a paradigm for complex, combinatorial responses of breast cancer models to atRA treatment, and illustrates the need to characterize RARE-independent responses to atRA in a variety of models.
Profiling of the transcriptional response to all-trans retinoic acid in breast cancer cells reveals RARE-independent mechanisms of gene expression.
Cell line
View SamplesTo determine whether immortalized cells derived from the rat SCN (SCN 2.2) retain intrinsic rhythm-generating properties characteristic of the SCN, oscillatory properties of the SCN2.2 transcriptome were analyzed and compared to those found in the rat SCN in vivo using rat U34A Affymetrix GeneChips. SCN2.2 cells were expanded in 6-well plates. At 6-hour interval across 2 circadian cycles, cells from single 6-well plates were harvested and pooled for total RNA extraction.
Circadian profiling of the transcriptome in immortalized rat SCN cells.
No sample metadata fields
View SamplesCAMTA3 is known to be involved in regulation of induction of early cold-responsive genes, CBF1 and CBF2 at cold conditions and of suppression of SA production at warm temperature.
Roles of CAMTA transcription factors and salicylic acid in configuring the low-temperature transcriptome and freezing tolerance of Arabidopsis.
Specimen part
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