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GSE29406
Homo sapiens
12 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Lactic acidosis and hypoxia are two prominent tumor microenvironmental stresses that are both known to exert important influences on gene expression and phenotypes of cancer cells. But very little is known about the cross-talk and interaction between these two stresses. We performed gene expression analysis of MCF7 cells exposed to lactic acidosis, hypoxia and combined lactic acidosis and hypoxia. We found the hypoxia response elicited under hypoxia was mostly abolished upon simultaneous exposure to lactic acidosis. The repression effects are due to loss of HIF-1 protein synthesis under lactic acidosis. In addition, we showed lactic acidosis strongly synergizes with hypoxia to activate the unfold protein response (UPR) and inflammation response which are highly similar to amino acid deprivation responses (AAR). The statistical factor analysis of hypoxia and lactic acidosis responses indicated that ATF4 locus, an important activator in the UPR/AAR pathway, is amplified in subsets of breast tumors and cancer cell lines. Varying ATF4 levels dramatically affect the ability to survive the post-stress recovery from hypoxia and lactic acidosis and may suggest its selection of ATF4 amplification in human cancers. These data suggest that lactic acidosis interacts with hypoxia by both inhibiting the canonical hypoxia response and while activating the UPR and inflammation response. Gain of ATF4 locus may offer survival advantages to allow successful adaptation to frequent fluctuations of oxygen and acidity in tumor microenvironment. Collectively, our studies have provided linkage between the short-term transcriptional responses to the long term selection of the DNA copy number alterations (CNAs) under tumor microenvironmental stresses.
Publication Title
Functional interaction between responses to lactic acidosis and hypoxia regulates genomic transcriptional outputs.
Sample Metadata Fields
Cell line
View Samples- Gallus gallus
- 94 Downloadable Samples
Illumina HiSeq 2500
Description
The pituitary gland is a neuroendocrine organ that is involved in several processes within the body such as metabolism, growth, immune function, and reproduction. Increased ambient temperatures are environmental stressor that leads to several welfare concerns in poultry production but also economic losses. Because of the involvement of the pituitary gland in several processes that are affected by heat stress, it is hypothesized this tissue''s gene expression will be impacted by heat stress. The objectives of the project are to (a) identify genes that constitue the pituitary gland when compared to other collected chicken tissues (Insert tissues) and (b) identify genes that respond to heat stress via differential expression analysis to better understand the chicken''s response to heat at the transcriptomic level. Overall design: Ross 708 broiler chickens were raised from day of hatch to day 42, typical market age, on the University of Delaware farm. Birds were placed into two separate houses, one thermoneutral house and one experimental (heat stress) house. Both houses were kept at 23 hours of light and 1 hour of dark and birds were placed on litter and given feed (meeting all NRC requirements) and water with ad libitum access. Both houses were kept at 35 degrees celsius for the first week and the temperature was decreased 5 degrees celsius each week until 25 degrees celsius. The thermoneutral hosue was maintained at 25 degrees celsius for the remainder of the study. Starting on day 21, the experimental house began a cyclical heat stress scheme with 8 hours per day of increased temperatures (35 - 37 degrees celsius) through completion of the trial at day 42. Necropsies were performed at several points throughout the trial (days 21, 22, 26, 32, and 42).
Publication Title
Transcriptomic changes throughout post-hatch development in Gallus gallus pituitary.
Sample Metadata Fields
Specimen part, Subject
View Samples- Gallus gallus
- 4 Downloadable Samples
- Illumina Genome Analyzer
Description
To investigate specific miRNA expression profiles of Marek's disease virus (MDV)-infected samples, we performed deep sequencing for miRNAs in four small RNA libraries, including MDV-infected tumorous spleen, MD lymphoma from liver, and non-infected spleen and lymphocytes from controls. A total of 7.76x106, 6.36x106, 6.36x106, and 7.60x106 counts were obtained in four libraries, respectively. The sequences were blasted with chicken and MDV genomes and miRBase 16.0 to identify known and novel miRNAs. In total, 187 and 16 known mature miRNAs were identified in the chicken and MDV, respectively. Deep sequencing detected 942 novel chicken miRNA candidates, of which 646 were in tumorous spleen. These results indicate that MDV infection induced new host miRNA candidates and increased diversity of miRNAs. Of 942 miRNA candidates, 276 of 533 were verified by customized microarray, and 17 of them were further confirmed by qPCR. Overall design: Four samples examined: MDV-infected tumorous spleen, MD lymphoma from liver, Non-infected spleen, Non-infected lymphocytes
Publication Title
A systematic analysis of miRNA transcriptome in Marek's disease virus-induced lymphoma reveals novel and differentially expressed miRNAs.
Sample Metadata Fields
Specimen part, Subject
View Samples- Gallus gallus
- 20 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
HD11 cells were stimulated with 1 ug/ml endotoxin from ST-798 for 1, 2, 4 and 8 hours
Publication Title
Unique genome-wide transcriptome profiles of chicken macrophages exposed to Salmonella-derived endotoxin.
Sample Metadata Fields
Cell line, Time
View Samples- Gallus gallus
- 3 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Avian pathogenic Escherichia coli (APEC) is considered one of the most common infectious bacterial diseases resulting in significant economic losses in poultry industry worldwide. In order to investigate the association between host immune resistance and miRNA expression in the pathogenic process induced by APEC, miRNA expression profiles in broilers spleen were performed by Solexa deep sequencing from three different treatment groups including non-challenged (NC), challenged-mild pathology (MD), and challenged-severe pathology (SV).In total, 3 462 706, 3 586 689, and 3 591 027 clean reads were obtained for NC, MD, and SV, respectively. After comparing the miRNA expression patterns, 27 differentially expressed miRNAs were identified among the three response groups, which included 13 miRNAs between NC and MD, 17 between NC and SV, and 14 between MD and SV. For these miRNAs, different expression in MD and SV suggested they may have resistance activity in APEC infection. Through integrated analysis of miRNA and mRNA expression patterns, 43 negative pairs between miRNA and mRNA (r < -0.80) were obtained. 4 miRNAs were validated to be significant negatively correlated to targets by quantitative real time PCR: gga-miR-21 (CLEC3B and GGTLA1), gga-miR-429 (TMEFF2, CDC20, SHISA2 and NOX4), gga-miR-146b (LAT2 and WNK1), and gga-miR-215 (C7 and ASL2). Additionally, the expression of gga-miR-21 and gga-miR-146b was significantly up-regulated by LPS induced in HD11 macrophage cell. In contrast, gga-miR-429 has no significant change. In summary, we present the first report that characterized the miRNA profiles of chicken spleen in response to APEC infection, and identified several candidate miRNAs which might accelerate host immune response through down-regulating their specific target genes. Overall design: Through the intra-air sac route into the left thoracic air sac, 240 non-vaccinated males at 4 weeks of age were challenged with 0.1 ml APEC O1 (10^8 colony forming units) and another 120 non-vaccinated males were non-challenged but treated with 0.1 ml PBS. Detailed information on the APEC O1 strain and challenge process was described by previously described study. Necropsy was performed at 1 day post challenge, and a summarized lesion ranging from 0 to 7 was determined for each APEC-challenged bird. Birds with lesions scoring 0-2 were regarded as mild infection, and those scoring 4-7 were designated as severe infection. The mild and severe pathology meant that birds were resistant and susceptible to APEC infection, respectively. Then, spleens from three groups, consisting of non-challenged, challenged-mild pathology and challenged-severe pathology were subjected to Solexa deep sequencing to investigate the dynamics of chicken miRNA expression.
Publication Title
Novel MicroRNA Involved in Host Response to Avian Pathogenic Escherichia coli Identified by Deep Sequencing and Integration Analysis.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Gallus gallus
- 17 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
Domestic chicken has been intensively studied because of its role as an efficient source of lean meat. However, commercial broilers resulting from genetic selection for rapid growth demonstrate detrimental traits, such as excess deposition of abdominal adipose tissue, metabolic disorders, and reduced reproduction. Therefore fast-growing broilers represent obese chickens compared to slow-growing egg layers (e.g, Leghorn) or wild strain of meat-type chickens (e.g., Fayoumi). Fayoumi chickens, originating from Egypt, represent a harder stain of chickens, which are more resistant to diseases. Leghorn chickens are the original breed of commercial U.S layers. Both lines were maintained highly inbred by Iowa State University poultry geneticists with an inbreeding coefficient higher than 0.95. Both Fayoumi and Leghorn demonstrated lean phenotype compared to broilers, and these three lines of chickens are genetically distant from each other.
Publication Title
Molecular and metabolic profiles suggest that increased lipid catabolism in adipose tissue contributes to leanness in domestic chickens.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Transcriptional profiling of oral keratinocytes was utilized to define the biological role of P. gingivalis SerB.
Publication Title
Role of Porphyromonas gingivalis SerB in gingival epithelial cell cytoskeletal remodeling and cytokine production.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
The concept of age-dependent host control of cancer development raises the natural question of how these effects manifest across the host tissue/organ types with which a tumor interacts, one important component of which is the aging immune system. To investigate this, changes in the spleen, an immune nexus in the mouse, was examined for its age-dependent interactive influence on the carcinogenesis process. The model is the C57BL/6 male mice (adolescent, young adult, middle-aged, and old or 68, 143, 551 and 736 days old respectively) with and without a syngeneic murine tumor implant. Through global transcriptome analysis, immune-related functions were found to be key regulators in the spleen associated with tumor progression as a function of age with CD2, CD3, CCL19, and CCL5 being the key molecules involved. Surprisingly, other than CCL5, all key factors and immune-related functions were not active in spleens from non-tumor bearing old mice. Our findings of age-dependent tumor-spleen signaling interaction suggest the existence of a global role of the aging host in carcinogenesis. Suggested is a new avenue for therapeutic improvement that capitalizes on the pervasive role of host aging in dictating the course of this disease.
Publication Title
Tumor-host signaling interaction reveals a systemic, age-dependent splenic immune influence on tumor development.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 32 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
The concept of age-dependent host control of cancer development raises the natural question of how these effects manifest across the host tissue/organ types with which a tumor interacts, one important component of which is the aging immune system. To investigate this, changes in the spleen, an immune nexus in the mouse, was examined for its age-dependent interactive influence on the carcinogenesis process. The model is the C57BL/6 male mice (adolescent, young adult, middle-aged, and old or 68, 143, 551 and 736 days old respectively) with and without a syngeneic murine tumor implant. Through global transcriptome analysis, immune-related functions were found to be key regulators in the spleen associated with tumor progression as a function of age with CD2, CD3, CCL19, and CCL5 being the key molecules involved. Surprisingly, other than CCL5, all key factors and immune-related functions were not active in spleens from non-tumor bearing old mice. Our findings of age-dependent tumor-spleen signaling interaction suggest the existence of a global role of the aging host in carcinogenesis. Suggested is a new avenue for therapeutic improvement that capitalizes on the pervasive role of host aging in dictating the course of this disease.
Publication Title
Tumor-host signaling interaction reveals a systemic, age-dependent splenic immune influence on tumor development.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage
View Samples- Gallus gallus
- 29 Downloadable Samples
- Illumina HiSeq 2500
Description
Climate change and disease have large negative impacts on poultry production, but little is known about the interactions of responses to these stressors in chickens. Fayoumi (heat and disease resistant) and broiler (heat and disease susceptible) chicken lines were stimulated at 22 days of age, using a 2x2x2 factorial design including: breed (Fayoumi or broiler), inflammatory stimulus [lipopolysaccharide (LPS) or saline], and temperature (35°C or 25°C). Transcriptional changes in spleens were analyzed using RNA-sequencing on the Illumina HiSeq 2500. Thirty-two individual cDNA libraries were sequenced (four per treatment) and an average of 22 million reads were generated per library. Stimulation with LPS induced more differentially expressed genes (DEG, log2 fold change = 2 and FDR = 0.05) in the broiler (N=283) than the Fayoumi (N=85), whereas heat treatment resulted in fewer DEG in broiler (N=22) compared to Fayoumi (N=107). The double stimulus of LPS+heat induced the largest numbers of changes in gene expression, for which broiler had 567 DEG and Fayoumi had 1471 DEG of which 399 were shared between breeds. Further analysis of DEG revealed pathways impacted by these stressors such as Remodelling of Epithelial Adherens Junctions due to heat stress, Granulocyte Adhesion and Diapedesis due to LPS, and Hepatic Fibrosis/Hepatic Stellate Cell Activation due to LPS+heat. The genes and pathways identified provide deeper understanding of the response to the applied stressors and may serve as biomarkers for genetic selection for heat and disease tolerant chickens. Overall design: At 22 days of age, divergent chicken breeds (Fayoumi and broiler) were treated with a thermal treatment (heat stress at 35C, or thermoneutral at 25C as a control) for 3.5 hours, then stimulated subcutaneously with an inflammatory stimulus (LPS, or saline as a control) for another 3.5 hours. Chickens were euthanized and spleens were harvested. A total of 32 indivudally coded cDNA libraries were prepared using TruSeq v2 library preparation kit which selects for polyA mRNA. In this 2x2x2 full factorial design with the factors of breed, thermal treatment, and inflammatory stimulus, there were a total of 8 treatment groups. Each treatment group had a total of 4 animal biological replicates. Therefore, a total of 32 individual barcoded samples were sequenced. A total of 8 individually barcoded cDNA libraries were sequenced per lane using the HiSeq Illumina 2500, and we used 4 lanes total. Reads were mapped to Galgal 2.0.
Publication Title
Unique genetic responses revealed in RNA-seq of the spleen of chickens stimulated with lipopolysaccharide and short-term heat.
Sample Metadata Fields
Subject
View Samples