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Gallus gallus
12 Downloadable Samples
Illumina Genome Analyzer
Description
Background: Heat stress triggers an evolutionarily conserved set of responses in cells. The transcriptome responds to hyperthermia by altering expression of genes to adapt the cell or organism to survive the heat challenge. RNA-seq technology allows rapid identification of environmentally responsive genes on a large scale. In this study, we have used RNA -seq to identify heat stress responsive genes in the chicken male white-leghorn hepat ocellular (LMH) cell line. Result: The transcripts of 812 genes were responsive to heat stress (p <0.01) with 235 genes up- regulated and 577 down-regulated following 2.5 hours of heat stress. Among the up- regulated were genes whose products function as chaperones, along with genes aff ecting collagen synthesis and deposition, transcription factors, chromatin remodelers and genes modulating the WNT and TGF-beta pathways. Predominant among the down-regulated genes were ones that affect DNA replication and repair along with chromosom al segregation. Many of the genes identified in this study have not been previously implicated in the heat stress response. Conclusion: These data extend our understanding of the transcriptome response to heat stress. Many of the identified biological processes and pathways likely function in adapting cells and organisms to hyperthermic stress. This study may provide important guides to future efforts attempting to improve species abilities to withstand heat stress through genome wide association studies and breeding. In addition, the genes down regulated by heat stress may provide important targets for improving hyperthemic treatment in cancer patients. Overall design: Cells were grown at either control ( 37oC) or heat stress (43oC) temperatures for 2.5 hours.
Publication Title
Transcriptome response to heat stress in a chicken hepatocellular carcinoma cell line.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Activators of innate immunity may have potential to combat a broad range of infectious agents. We report that treatment with bacterial flagellin prevented rotavirus (RV) infection in mice and cured chronically RV-infected mice. Protection was independent of adaptive immunity and interferon (IFN, type I and II) and required flagellin receptors Toll-like receptor 5 (TLR5) and NOD-like receptor C4 (NLRC4). Flagellin-induced activation of TLR5 on dendritic cells elicited production of the cytokine interleukin (IL)-22, which induced a protective gene expression program in intestinal epithelial cells. Flagellin also induced NLRC4-dependent production of IL-18 and immediate elimination of RV-infected cells. Administration of IL-22 and IL-18 to mice fully recapitulated the capacity of flagellin to prevent or eliminate RV infection, and thus holds promise as a broad-spectrum antiviral agent. Overall design: Total mRNA from intestinal epithelial cells of Rag1-/- mice treated with PBS, IL-18, IL-22 or IL-22/IL-18 was assayed for RNA sequencing.
Publication Title
Viral infection. Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Illumina Genome Analyzer II
Description
We used RNA sequencing to identify the RBFOX1 splicing network at a genome-wide level in primary human neural stem cells during differentiation. We observe that RBFOX1 regulates a large set of alternative splicing events implicated in neurogenesis and cell maintenance. Subsequent alterations in gene expression define an additional transcriptional network regulated by RBFOX1 involved in neurodevelopmental pathways remarkably parallel to those affected by splicing. Overall design: RNA sequencing at a 75bp single-end read scale was performed using polyA-enriched RNA from 5 biological replicates of primary human neural progenitor cell lines generated by lentiviral-mediated knockdown of GFP (control) or RBFOX1 and differentiated for 4 weeks.
Publication Title
RBFOX1 regulates both splicing and transcriptional networks in human neuronal development.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Ion Torrent Proton
Description
We previously reported a pathogenic de novo W342 mutation in the transcriptional corepressor CtBP1 in four independent patients with neurodevelopmental disabilities. Here, we report the clinical phenotypes of seven additional individuals with the same recurrent de novo CtBP1 mutation. Within this cohort we identified consistent CtBP1-related phenotypes of intellectual disability, ataxia, hypotonia and tooth enamel defects present in all patients. The W342 mutation in CtBP1 is located within a region implicated in a high affinity-binding cleft for CtBP-interacting proteins. Unbiased proteomic analysis demonstrated reduced interaction of several chromatin modifying factors with the CtBP1 W342 mutant. Genome-wide transcriptome analysis in human glioblastoma cells lines expressing -CtBP1 R342 (wt) or W342 mutation revealed changes in the expression profiles of genes controlling multiple cellular processes. Patient-derived dermal fibroblasts were found to be more sensitive to apoptosis during acute glucose deprivation compared to controls. Glucose deprivation strongly activated the BH3-only pro-apoptotic gene NOXA, suggesting a link between enhanced cell death and NOXA expression in patient fibroblasts. Our results suggest that context-dependent relief of transcriptional repression of the CtBP1 mutant W342 allele may contribute to deregulation of apoptosis in target tissues of patients leading to neurodevelopmental phenotypes. Overall design: Total RNA samples were isolated from 3 different cultures of HTB17 cells that overexpressed CtBP1 wt or the pathogenic mutant, W342 and analyzed by high- throughput RNA sequencing.
Publication Title
A pathogenic CtBP1 missense mutation causes altered cofactor binding and transcriptional activity.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Plac1 is an X-linked (Xq26) trophoblast gene expressed at high levels in the placenta, at low levels in the testis, but not in other normal somatic tissues. However, it is re-expressed in several malignancies, including breast, colon, lung, gastric, liver and endometrial cancers as well as in most human cancer cell lines. Plac1 contains HLA-A2-restricted epitopes capable of eliciting a cytotoxic T lymphocyte (CTL) response against human breast cancer cells, and colorectal cancer patients with a Plac1-specific CTL response demonstrate long-term survival. To explore the role of Plac1 in cancer, mouse mammary tumor E0771 cells expressing high levels of Plac1 were transduced with a lentivirus expressing a Plac1 shRNA (E0771/shPlac1).
Publication Title
Plac1 Is a Key Regulator of the Inflammatory Response and Immune Tolerance In Mammary Tumorigenesis.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Congenital heart defects (CHD) are one of the most common defects in offspring of diabetic mothers. There is a clear association between maternal diabetes and CHD; however the underlying molecular mechanism remains unknown. We hypothesized that maternal diabetes affects with the expression of early developmental genes that regulate the essential developmental processes of the heart, thereby resulting in the pathogenesis of CHD. We analyzed genome-wide expression profiling in the developing heart of embryos from diabetic and control mice by using the oligonucleotide microarray. Microarray analysis revealed that a total of 878 genes exhibited more than 1.5 fold changes in expression level in the hearts of experimental embryos in either E13.5 or E15.5 compared with their respective controls. Expression pattern of genes that is differentially expressed in the developing heart was further examined by the real-time reverse transcriptase-polymerase chain reaction. Several genes involved in a number of molecular signaling pathways such as apoptosis, proliferation, migration and differentiation in the developing heart were differentially expressed in embryos of diabetic pregnancy. It is concluded that altered expression of several genes involved in heart development may contribute to CHD in offspring of diabetic mothers.
Publication Title
Differential gene expression profiles during embryonic heart development in diabetic mice pregnancy.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Pro-inflammatory cytokines were shown to promote growth and survival of cancerous cells. TNF induced RelA:p50 NF-B dimer via the canonical pathway is thought to link inflammation with cancer. Integrating biochemical and computational studies we identify that deficiency of non-canonical signal transducer p100 triggers a positive autoregulatory loop, which instead perpetuates an alternate RelB:p50 containing NF-B activity upon TNF treatment. TNF stimulated RelB:p50 dimer is sufficient for mediating NF-B target gene-expressions and suppressing apoptotic cellular death independent of principal NF-B subunit RelA. We further demonstrate that activating mutations in non-canonical NF-B module deplete multiple myeloma cells of p100, thereby, provoking autoregulatory RelB:p50 activation. Finally, autoregulatory control reinforces protracted pro-survival NF-B response, albeit comprising of RelB:p50, upon TNF priming that protects myeloma cells with dysfunctional p100 from subsequent apoptotic insults. In sum, we present evidence for positive autoregulation mediated through the NF-B system and its potential involvement in human neoplasm.
Publication Title
Non-canonical NFκB mutations reinforce pro-survival TNF response in multiple myeloma through an autoregulatory RelB:p50 NFκB pathway.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Whole transcript analysis of amyloid beta 42 (Aβ42)-induced SH-SY5Y cells in control and treated groups (curcumin, piperine and combination therapy) were assessed using microarray profiling. A number of up-regulated and down-regulated genes were altered in sample-specific group.
Publication Title
Explicating anti-amyloidogenic role of curcumin and piperine via amyloid beta (A<i>β</i>) explicit pathway: recovery and reversal paradigm effects.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
West Nile virus (WNV) is the most important cause of endemic encephalitis in the USA. Strikingly, only a small percentage of patients develop clinical disease and of these patients, approximately 1 out of 150 patients develops encephalitis. The basis for this great variability in disease outcome is unknown, but may be related to the innate immune response. Innate immune responses, critical for control of WNV infection, are initiated by signaling through pathogen recognition receptors (PRR) such as RIG-I and MDA5. IPS-1 is a key adaptor in generating a PRR-dependent interferon response.. Here we show that IPS-1 deficiency in hematopoietic cells resulted in increased mortality and delayed WNV clearance from the brain. In IPS-1-/- mice, a dysregulated immune response was detected, characterized by a massive influx of macrophages and virus-specific T cells into the infected brain. These T cells were multifunctional and were able to lyse peptide-pulsed target cells in vitro. However, virus-specific T cells in the infected IPS-1-/- brain exhibited lower functional avidity than those in C57BL/6 brains, possibly contributing to less efficient virus clearance. The presence of virus-specific memory T cells was also not protective. We also show that macrophages were increased in numbers in the IPS-1-/- brain. Both macrophages and microglia exhibited an activated phenotype. Microarray analyses showed the preferential upregulation of genes associated with leukocyte activation and inflammation. Together, these results demonstrate the critical role that hematopoietic cell expression of Type 1 interferon and other IPS-1-dependent molecules have in WNV clearance and in regulating the inflammatory response.
Publication Title
MAVS Expressed by Hematopoietic Cells Is Critical for Control of West Nile Virus Infection and Pathogenesis.
Sample Metadata Fields
Specimen part, Time
View Samples
GSE54054- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Hepatocellular carcinoma (HCC) is a deadly disease, often unnoticed till the late stages, where treatment options become limited. Thus, there is a critical need to identify early biomarkers for detection of the developing HCC, as well as molecular pathways that would be amenable to therapeutic intervention. While efforts using human serum and tissues from late stage patients have been undertaken, progress has been limited. We have therefore explored the possibility of utilizing established mouse models for the discovery of biomarkers, as well as to understand in a systematic manner the molecular pathways that are progressively deregulated by the various etiological factors in contributing to HCC formation. As an initial effort, we have used the Hepatitis B surface antigen (HBsAg) transgenic mice as a hepatitis model, which have been exposed to aflatoxin B1 (AFB1). In this report, we present the initial findings from a extensive longitudinal study, which confirms the synergistic effect of both these etiological factors, with a gender bias towards male mice. Tumors from the mouse models were validated both histologically as well as by molecular transcriptome analysis by comparison with human HCCs. In addition, using these models, we have identified carnitine as a novel biomarker for HCC development, which was again validated using human HCC samples. Conclusion: This study therefore highlights the utility of these mouse models in identifying biomarkers for detection of human HCCs, as well as for the systematic analysis of molecular pathways that are affected by various etiological agents during the progression of HCC from an untransformed hepatocyte, which could provide novel options for targeted therapy.
Publication Title
Molecular characterization of hepatocarcinogenesis using mouse models.
Sample Metadata Fields
Specimen part
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