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GSE21071
Sus scrofa
40 Downloadable Samples
Affymetrix Porcine Genome Array (porcine)
Description
Lung disease causes most of the morbidity and mortality in cystic fibrosis (CF). However, understanding its pathogenesis has been hindered by lack of an animal model with characteristic features of CF. To overcome this problem, we recently generated pigs with targeted CFTR genes. We now report that within months of birth, CF pigs spontaneously develop hallmark features of CF lung disease including airway inflammation, remodeling, mucus accumulation, and infection. Their lungs contained multiple bacterial species, suggesting an equal opportunity host defense defect. In humans, the temporal and/or causal relationships between inflammation and infection have remained uncertain. To investigate these processes, we studied newborn pigs. Their lungs showed no inflammation, but were less often sterile than controls. Moreover, after intrapulmonary bacterial challenge, CF pigs failed to eradicate bacteria as effectively as wild- type pigs. These results suggest that impaired bacterial elimination is the pathogenic event that initiates a cascade of inflammation and pathology in CF lungs. Finding that CF pigs have a bacterial host defense defect within hours of birth provides an exciting opportunity to further investigate pathogenesis and to test therapeutic and preventive strategies before secondary consequences develop.
Publication Title
Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Analysis of estrogen receptor (ER)-positive MCF7 cell total RNA expression and polysome-assiciated RNA expression following treatment with estradiol (E2) and vehicle (etoh).
Publication Title
Estrogen coordinates translation and transcription, revealing a role for NRSF in human breast cancer cells.
Sample Metadata Fields
Cell line
View Samples- Saccharomyces cerevisiae
- 83 Downloadable Samples
Illumina HiSeq 2500, Illumina HiSeq 2000, Illumina Genome Analyzer IIx
Description
Purpose: The ability to rationally manipulate the transcriptional states of cells would be of great use in medicine and bioengineering. We have developed a novel algorithm, NetSurgeon, which utilizes genome-wide gene regulatory networks to identify interventions that force a cell toward a desired expression state. Results: We used NetSurgeon to select transcription factor deletions aimed at improving ethanol production in S. cerevisiae cultures that are catabolizing xylose. We reasoned that interventions that move the transcriptional states of cells utilizing xylose toward the fermentative state typical of cells that are producing ethanol rapidly (while utilizing glucose) might improve xylose fermentation. Some of the interventions selected by NetSurgeon successfully promoted a fermentative transcriptional state in the absence of glucose, resulting in strains with a 2.7-fold increase in xylose import rates, a 4-fold improvement in xylose integration into central carbon metabolism, or a 1.3-fold increase in ethanol production rate. Conclusions: We conclude by presenting an integrated model of transcriptional regulation and metabolic flux that will enable future metabolic engineering efforts aimed at improving xylose fermentation to prioritize functional regulators of central carbon metabolism. Overall design: Mutant and wildtype S. cerevisiae cells were put into 48 hour aerobic batch fermentations of synthetic complete medium supplmented with 2% glucose and 5% xylose and culture samples were taken at 4 hours and 24 hours for transcriptional profiling performed by RNA-Seq analysis. In addition, wildtype S. cerevisiae cells were grown in various single carbon sources for 12 hours and culture samples were taken for transcriptional profiling performed by RNA-Seq analysis.
Publication Title
Model-based transcriptome engineering promotes a fermentative transcriptional state in yeast.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 27 Downloadable Samples
- Illumina HiSeq 2000
Description
Metastasis-initiating cells dynamically adapt to the distinct microenvironments of different organs, but these early adaptations are poorly understood due to the limited sensitivity of in situ transcriptomics. We developed fluorouracil-labeled RNA sequencing (Flura-seq) for in situ analysis with unprecedented sensitivity. Flura-seq utilizes cytosine deaminase (CD) to convert fluorocytosine to fluorouracil, covalently labeling nascent RNA for purification and sequencing. Flura-seq revealed that breast cancer micrometastases in lung and brain exhibit unique, reversible gene signatures depending on the microenvironment. Specifically, the mitochondrial electron transport Complex I and the NRF2-driven antioxidant programs were induced in oxygen-rich pulmonary micrometastases, compared to mammary tumors or brain micrometastases. Loss of Complex I activity, and antioxidant supplementation potentiated pulmonary metastatic growth. We confirm lung metastasis-specific NRF2 overexpression in clinical samples, thus validating Flura-seq's utility in identifying clinically actionable microenvironmental adaptations in early metastasis. The sensitivity, robustness and economy of Flura-seq are broadly applicable beyond cancer research. Overall design: Examination of 5-FU labeled RNAs in cancer cells present in different organs
Publication Title
Flura-seq identifies organ-specific metabolic adaptations during early metastatic colonization.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Few studies have investigated heterogeneity of selection response in replicate lines subjected to equivalent selection. We developed 4 replicate lines of mice based on high levels of voluntary wheel running (high runner or HR lines) while also maintaining 4 non-selected control lines. This led to the unexpected discovery of the HR mini-muscle (HRmini) phenotype, recognized by a 50% reduction in hindlimb muscle mass, which became fixed in 1 of the 4 HR selected lines.
Publication Title
Gene expression profiling of gastrocnemius of "minimuscle" mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
How organ-specific metastatic traits accumulate in primary tumors remains unknown. We identified a role of the primary tumor stroma in selecting breast cancer cells that are primed for metastasis in the bone. A fibroblast-rich stroma in breast tumors creates a microenvironment that is similar to that of bone metastases in its abundance of the cytokines CXCL12 and IGF1. Heterogeneous breast cancer cell populations growing in such mesenchymal environment evolve towards a preponderance of clones that thrive on CXCL12 and IGF1. Fibroblast-driven selection of bone metastatic clones in mammary tumors is suppressed by CXCL12 and IGF1 receptor inhibition. Thus, a fibroblast-rich stroma in breast tumors can pre-select bone metastatic seeds, promoting the evolution of metastatic traits and the interplay between a primary tumor and its distant metastases.
Publication Title
Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Metastatic relapse of breast cancer and other tumor types usually occurs several years after surgical resection of the primary tumor. Early dissemination of tumor cells followed by an extended period of dormancy is thought to explain this prevalent clinical behavior. By using a gain-of-function retroviral cDNA screen in the mouse, we found that Coco, a secreted antagonist of TGF-beta ligands, induces solitary mammary carcinoma cells that have extravasated in the lung stroma to exit from dormancy. Mechanistic studies demonstrate that Coco awakens dormant metastasis-initiating cells by blocking stroma-derived Bone Morphogenetic Proteins. Inhibition of canonical BMP signaling reverses the commitment to differentiation of these cells and enhances their self-renewal and tumor-initiation capacity. Expression of Coco induces a discrete gene expression signature strongly associated with metastatic relapse to the lung but not to the bone or brain in primary patients samples. Accordi ngly, silencing of Coco does not inhibit metastasis to the bone or brain in mouse models. These findings suggest that metastasis-initiating cells require the self-renewal capability typically associated with stem cells in order to exit from dormancy and identify Coco as a master regulator of this process.
Publication Title
The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Spleen and lymph node dendritic cells have a differential capacity do induce and retain iTreg cells. Therefore we performed a comparative analysis of the dendritic cells derived from these two compartments to identify the responsible genes
Publication Title
Migratory, and not lymphoid-resident, dendritic cells maintain peripheral self-tolerance and prevent autoimmunity via induction of iTreg cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
CXCL12 and IGF1 are key secreting molecules produced by cancer-associated fibroblasts in breast cancer. These factors promote the survival of disseminated cancer cells in the bone marrow. To assess the combined responses elicited by CXCL12 and IGF1, we examined the translating transcriptome of cancer cells in response to these two factors by Translating Ribosome Affinity Purification (TRAP)-RNAseq. Overall design: MDA-MB-231 cells were engineered to express an EGFP-tagged version of ribosomal protein L10a. This allows the retrieval of polysome-associated mRNA by anti-GFP pull down (TRAP) and profiling the translating transcriptome by RNAseq. EGFP-L10a+ cancer cells were serum starved (0.2% serum) for 24 hours, and then treated with CXCL12 (30ng/mL) + IGF1 (10ng/mL) or CXCL12 (300ng/mL) + IGF1 (100ng/mL) for 6hrs. Two biological replicates were profiled for each condition.
Publication Title
Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Anas platyrhynchos, Gallus gallus
- 8 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
While infection of chickens with highly pathogenic avian influenza (HPAI) H5N1 subtypes often leads to complete mortality within 24 to 48 h, infection of ducks in contrast causes mild or no clinical signs. Rapid onsets of fatal disease in chickens, but with no evidence of severe clinical symptoms in ducks, suggest underlying differences in their innate immune mechanisms. To understand the molecular basis for such difference, chicken and duck primary lung cells, infected with a low-pathogenicity avian influenza (LPAI) and two HPAI H5N1 viruses, were subjected to RNA expression profiling using Affymetrix Chicken GeneChip arrays.
Publication Title
Highly pathogenic avian influenza virus infection in chickens but not ducks is associated with elevated host immune and pro-inflammatory responses.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples