The objective of this study was to determine the effect of Thyroid Hormone Responsive Protein Spot14 (Spot14) overexpression on the gene expression profiles of tumors from MMTV-Neu mice. Hemizygous MMTV-Neu and MMTV-Spot14 mice were bred and 1 cm tumors from Neu control or Neu/Spot14 bitransgenic offspring were profiled using Affymetrix gene arrays. Tumors from Neu/Spot14 mice emerged significantly earlier than controls, but expressed many genes associated with lactogenic differentiation and were not highly metastatic. These results from the mouse model are consistent with observations from primary human breast tumors, which indicate that high Spot14 gene expression was directly correlated with a luminal subtype and a positive ER status. Overexpression of Spot14 in cultured mammary epithelial cells stimulated proliferation but not differentiation. Together, these data suggest that, in vivo, Spot14 is expressed in well-differentiated cells, and promotes the expansion of this population in the context of oncogenic signaling pathway activation.
Modulation of tumor fatty acids, through overexpression or loss of thyroid hormone responsive protein spot 14 is associated with altered growth and metastasis.
Specimen part
View SamplesThe objective of this study was to determine the effect of Thyroid Hormone Responsive Protein Spot14 (Spot14) loss on the gene expression profiles of tumors from MMTV-Polyomavirus middle-T antigen (PyMT) mice. MMTV-PyMT/S14-heterozygous mice were crossed with S14-heterozygous mice and 1 cm tumors from MMTV-PyMT control (wild-type S14) or MMTV-PyMT/S14-null offspring were profiled using Affymetrix gene arrays. Tumor latency was not different between groups; however, tumors lacking S14 grew significantly slower than control tumors. Loss of S14 also decreased the levels of de novo synthesized fatty acids in mammary tumors. In additional studies, performed on MMTV-Neu mice, we found that S14 overexpression was associated with increased tumor cell proliferation and elevated levels of tumor fatty acids. Gene expression profiling revealed that S14 loss and overexpression in mouse mammary tumors altered pathways associated with proliferation and metabolism. This study provides important information about the role of S14 in mammary tumorigenesis and tumor metabolism.
Modulation of tumor fatty acids, through overexpression or loss of thyroid hormone responsive protein spot 14 is associated with altered growth and metastasis.
No sample metadata fields
View SamplesMicroRNA microarrays and RNA expression arrays were used to identify functional signaling between neural stem cell progenitor cells (NSPC) and brain endothelial cells (EC) that are critical during embryonic development and tissue repair following brain injury.
The role of microRNAs in neural stem cell-supported endothelial morphogenesis.
Specimen part, Disease, Treatment
View SamplesBackground: Single-cell RNA-Seq can be a valuable and unbiased tool to dissect cellular heterogeneity, despite the transcriptome’s limitations in describing higher functional phenotypes and protein events. Perhaps the most important shortfall with transcriptomic ‘snapshots’ of cell populations is that they risk being descriptive, only cataloging heterogeneity at one point in time, and without microenvironmental context. Studying the genetic (‘nature’) and environmental (‘nurture’) modifiers of heterogeneity, and how cell population dynamics unfold over time in response to these modifiers is key when studying highly plastic cells such as macrophages. Results: We introduce the programmable PolarisTM microfluidic lab-on-chip for single-cell sequencing, which performs live-cell imaging while controlling for the culture microenvironment of each cell. Using gene-edited macrophages we demonstrate how previously unappreciated knockout effects of SAMHD1, such as an altered oxidative stress response, have a large paracrine signaling component. Furthermore, we demonstrate single-cell pathway enrichments for cell cycle arrest and APOBEC3G degradation, both associated with the oxidative stress response and altered proteostasis. Interestingly, SAMHD1 and APOBEC3 are both HIV-1 inhibitors (‘restriction factors’), with no previously known co-regulation. Conclusion: As single-cell methods continue to mature, so will the ability to move beyond simple ‘snapshots’ of cell populations towards studying the determinants of population dynamics. By combining single-cell culture, live-cell imaging, and single-cell sequencing, we have demonstrated the ability to study cell phenotypes and microenvironmental influences. It’s these microenvironmental components - ignored by standard single-cell workflows - that likely determine how macrophages, for example, react to inflammation and form treatment resistant HIV reservoirs. Overall design: Stem cell derived macrophages (wildtype and SAMHD1 knockout) were single-cell cultured for 1h or 8h under for different media conditions (with/without lipopolysaccharide, with/without conditioned media to account for inter-macrophage signalling)
The nature and nurture of cell heterogeneity: accounting for macrophage gene-environment interactions with single-cell RNA-Seq.
Specimen part, Cell line, Subject
View SamplesWe performed a transcriptomic analysis to identify genes differentially transcribed in the maize stem upon corn borer feeding and treatment with insects regurgitates by using the MACE (Massive Analysis of cDNA Ends) technology. Overall design: Two comparisons were performed: Insect chewing vs control and Regurgitate+wounding vs wounding in three biological replicates per treatment
Maize Stem Response to Long-Term Attack by <i>Sesamia nonagrioides</i>.
Specimen part, Treatment, Subject
View SamplesA subset of our SLNs would be upregulated by Nutlin-3 and down-regulated by 5-FU and that this differential regulation could potentially explain how cell fate choice is determined
ATM and MET kinases are synthetic lethal with nongenotoxic activation of p53.
Cell line, Treatment
View SamplesRNA-Seq analysis was performed to assess how a glucose-supplemented diet and/or a hyl-2 mutation altered the transcriptome. Comparison analysis of transcripts associated with anoxia sensitive animals (hyl-2(tm2331) mutation or a glucose diet) revealed 199 common transcripts encoded by genes with known or predicted functions involving innate immunity, cuticle function (collagens) or xenobiotic and endobiotic phase I and II detoxification system. Overall design: mRNA profiles of OP50-fed C. elegans, glucose-fed C. elegans (N2 strain), OP50-fed C. elegans altered in ceramide metabolism (due to a hyl-2(tm2031) mutation), and glucose-fed C. elegans altered in ceramide metabolism were generated by RNA-Seq, in triplicate, using an Illumina HiSeq2000. Transcriptome data were then used for a comprehensive quantitative analysis of differential gene regulation in hyl-2(tm2031) and glucose-fed C. elegans.
Glucose or Altered Ceramide Biosynthesis Mediate Oxygen Deprivation Sensitivity Through Novel Pathways Revealed by Transcriptome Analysis in Caenorhabditis elegans.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Aneuploidy, oncogene amplification and epithelial to mesenchymal transition define spontaneous transformation of murine epithelial cells.
Sex, Specimen part
View SamplesHuman epithelial cancers are defined by a recurrent distribution of specific chromosomal aneuploidies. In our model system, mouse bladder and kidney epithelial cells spontaneously immortalize, transform and become tumorigenic after prolonged culture. We assessed genome and transcriptome alterations and found wide-spread aneuploidy, early transcriptional deregulation, and massive genomic dereguation of the cellular transcriptome.
Aneuploidy, oncogene amplification and epithelial to mesenchymal transition define spontaneous transformation of murine epithelial cells.
Sex, Specimen part
View SamplesWhile the salutary effects of exercise training on conduit artery endothelial cells have been reported in animals and humans with cardiovascular risk factors or disease, whether a healthy endothelium is alterable with exercise training is less certain. The purpose of this study was to evaluate the impact of exercise training on transcriptional profiles in normal endothelial cells using a genome-wide microarray analysis. Brachial and internal mammary endothelial gene expression was compared between a group of healthy pigs that exercise-trained for 16-20 weeks (n=8) and a group that remained sedentary (n=8). We found that a total of 130 genes were up regulated and 84 genes down regulated in brachial artery endothelial cells with exercise training. In contrast, a total of 113 genes were up regulated and 31 genes down regulated in internal mammary artery endothelial cells (>1.5-fold and false discovery rate<15%). Although there was an overlap of 66 genes (59 up regulated and 7 down regulated with exercise training) between the brachial and internal mammary arteries, the identified endothelial gene networks and biological processes influenced by exercise training were distinctly different between the brachial and internal mammary arteries. These data indicate that a healthy endothelium is indeed responsive to exercise training and support the concept that the influence of physical activity on endothelial gene expression is not homogenously distributed throughout the vasculature.
Impact of exercise training on endothelial transcriptional profiles in healthy swine: a genome-wide microarray analysis.
Specimen part, Treatment
View Samples