The transcriptome of zebrafish embryos treated with a Nodal signaling inhibitor at sphere stage, which causes neural tube defects, is compared to those treated at 30% epiboly, which does not. Overall design: Transcriptomic analysis of differential gene expression of key developmental pathways under differing inhibitory treatments.
Identification of transcripts potentially involved in neural tube closure using RNA sequencing.
No sample metadata fields
View SamplesSocial experience influences multiple behaviors of many animal species, including aggression. Social isolation often increases aggressiveness. To investigater the molecular basis of social influences on aggressiveness, we performed comparative gene expression profiling on heads from 6-day-old, single-housed, more aggressive and group-housed, less aggressive male flies.
A common genetic target for environmental and heritable influences on aggressiveness in Drosophila.
No sample metadata fields
View SamplesThe Wnt gene family is an evolutionarily conserved group of proteins that regulate cell growth, differentiation, and stem cell self-renewal. Aberrant Wnt signaling in human breast tumors has been proposed to be an attractive drug target, especially in the basal-like subtype where canonical Wnt signaling is both enriched and predictive of poor clinical outcomes. The development of effective Wnt based therapeutics, however, has been slowed in part by a limited understanding of the context dependent nature with which these aberrations influence breast tumorigenesis. We recently reported that MMTV-Wnt1 mice, which are an established model for studying Wnt signaling in breast tumors, develop two subtypes of tumors by gene expression classification: Wnt1-EarlyEx and Wnt1-LateEx. Here, we extend this initial observation and show that Wnt1-EarlyEx tumors had high expression of canonical Wnt, non-canonical Wnt, and EGFR signaling pathway signatures. Therapeutically, Wnt1-EarlyEx tumors had a dynamic reduction in tumor volume when treated with an EGFR inhibitor. Wnt1-EarlyEx tumors also had primarily Cd49fpos/Epcamneg FACS profiles, but were unable to be serially transplanted into wild-type FVB female mice. Wnt1-LateEx tumors, conversely, had a bloody gross pathology, which was highlighted by the presence of 'blood lakes' by H&E staining. These tumors had primarily Cd49fpos/Epcampos FACS profiles, but also contained a secondary Cd49fpos/Epcamneg subpopulation. Wnt1-LateEx tumors were enriched for activating Hras1 mutations and were capable of reproducing tumors when serially transplanted into wild-type FVB female mice. This study definitely shows that the MMTV-Wnt1 mouse model produces two phenotypically distinct subtypes of mammary tumors. Importantly, these subtypes differ in their therapeutic response to an EGFR inhibitor, suggesting that a subset of human tumors with aberrant Wnt signaling may also respond to erlotinib. Overall design: Agilent gene expression microarrays were performed comparing RNA from FVB/n MMTV-Wnt1 mammary tumors to a common mouse reference sample. Agilent CGH microarrays were performed comparing DNA from FVB/n MMTV-Wnt1 mammary tumors to DNA from FVB wild-type mice. RNAseq libraries were prepared from FVB/n MMTV-Wnt1 mammary tumors using a TruSeq RNA kit before being submitted to the Lineberger Comprehensive Cancer Center Genomics Core to be run on the Illumina HiSeq 2000.
The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor.
Specimen part, Subject
View SamplesWe developed a mouse model that captures radiation effects on host biology by transplanting unirradiated Trp53 null mammary tissue to sham or irradiated hosts. Gene expression profiles of tumors that arose in irradiated mice are distinct from those that arose in nave hosts.
Murine microenvironment metaprofiles associate with human cancer etiology and intrinsic subtypes.
Specimen part
View SamplesThe goal of this study is to determine the effects of adipose-specific Glut4 overexpression or knockout on changes in adipose tissue global gene expression
A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism.
Sex, Age
View SamplesWe use RNA-sequencing to generate gene expression profiles of fetal mammary cells that have been induced to overexpress Sox10. These data highlight multiple important molecular mechanisms that are altered in response to this perturbation, and offer a resource to probe the basis of the stem/progenitor and EMT-like functions that are mediated by Sox10 in mammary cells. Overall design: Expression profiling of fetal mammary cells that express ectopic levels of Sox10
Sox10 Regulates Stem/Progenitor and Mesenchymal Cell States in Mammary Epithelial Cells.
No sample metadata fields
View SamplesWe use RNA-sequencing to generate gene expression profiles of fetal mammary cells with unique sorting strategies. These analyses reveal that sorting fetal mammary cells with Sox10 and EpCAM sorting markers provides a stroma-free fMaSC-enriched cell population. The gene expression profiling of these cells offers a resources to probe the molecular mechanisms that specify this unique cell state. Overall design: Examination of 2 different sorting strategies for fetal mammary cells
Sox10 Regulates Stem/Progenitor and Mesenchymal Cell States in Mammary Epithelial Cells.
No sample metadata fields
View SamplesProtein synthesis belongs to the most energy consuming processes in the cell. Lowering oxygen tension below normal (hypoxia) causes a rapid inhibition of global mRNA translation due to the decreased availability of energy. Interestingly, subsets of mRNAs pursue active translation under such circumstances. In human fibrosarcoma cells (HT1080) exposed to prolonged hypoxia (36 h, 1% oxygen) we observed that transcripts are either increasingly or decreasingly associated with ribosomes localized at the endoplasmic reticulum (ER). In a global setting it turned out that only 31% of transcripts showing elevated total-RNA levels were also increasingly present at the ER in hypoxia. These genes, regulated by its expression as well as its ER-localization, belong to the gene ontologys hypoxia response, glycolysis and HIF-1 transcription factor network supporting the view of active mRNA translation at the ER during hypoxia. Interestingly, a large group of RNAs was found to be unchanged at the expression level, but translocate to the ER in hypoxia. Among these are transcripts encoding translation factors and >180 ncRNAs. In summary, we provide evidence that protein synthesis is favoured at the ER and, thus, partitioning of the transcriptome between cytoplasmic and ER associated ribosomes mediates adaptation of gene expression in hypoxia.
Hypoxia-induced gene expression results from selective mRNA partitioning to the endoplasmic reticulum.
Specimen part, Cell line
View SamplesTherapies targeting the type I insulin-like growth factor receptor (IGF-1R) have not been developed with predictive biomarkers to identify tumors with receptor activation. We have previously shown that the insulin receptor substrate (IRS) adaptor proteins are necessary for linking IGF1R to downstream signaling pathways and the malignant phenotype in breast cancer cells. The purpose of this study was to identify gene expression profiles downstream of IGF1R and its two adaptor proteins. IRS-null breast cancer cells (T47D-YA) were engineered to express IRS-1 or IRS-2 alone and their ability to mediate IGF ligand-induced proliferation, motility, and gene expression determined. Global gene expression signatures reflecting IRS adaptor specific and primary vs. secondary ligand response were derived (Early IRS-1, Late IRS-1, Early IRS-2 and Late IRS-2) and functional pathway analysis examined. IRS isoforms mediated distinct gene expression profiles, functional pathways, and breast cancer subtype association. For example, IRS-1/2-induced TGFb2 expression and blockade of TGFb2 abrogated IGF-induced cell migration. In addition, the prognostic value of IRS proteins was significant in the luminal B breast tumor subtype. Univariate and multivariate analyses confirmed that IRS adaptor signatures correlated with poor outcome as measured by recurrence-free and overall survival. Thus, IRS adaptor protein expression is required for IGF ligand responses in breast cancer cells. IRS-specific gene signatures represent accurate surrogates of IGF activity and could predict response to anti-IGF therapy in breast cancer.
Insulin Receptor Substrate Adaptor Proteins Mediate Prognostic Gene Expression Profiles in Breast Cancer.
Cell line
View SamplesWe used microarray analysis to identify differences in gene expression levels, in liver and in quadriceps skeletal muscle, between 18h (overnight) fasted WT control and Kruppel-like factor 15 (KLF15)-null mice.
Regulation of gluconeogenesis by Krüppel-like factor 15.
No sample metadata fields
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