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GSE55606
Mus musculus
11 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Molecular profiling of infiltrating monocyte-derived macrophages versus resident kupffer cells following acute liver injury
Publication Title
Infiltrating monocyte-derived macrophages and resident kupffer cells display different ontogeny and functions in acute liver injury.
Sample Metadata Fields
Specimen part, Disease, Time
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Viruses lack the basic machinery needed to replicate and therefore must hijack host metabolism to propagate. Virus-induced metabolic alterations have yet to be systematically studied in the context of the host transcriptional regulation, offering insight into host-pathogen metabolic interplay. In this work we identified Hepatitis C Virus (HCV)-responsive regulators by coupling system-wide metabolic flux analysis with targeted perturbation of nuclear receptors in primary human hepatocytes. We find HCV-induced up-regulation of glycolysis, ketogenesis and drug metabolism, controlled by activation of HNF4, PPAR, FXR and PXR, respectively. Pharmaceutical inhibition of HNF4 reversed HCV-induced glycolysis, blocking viral replication while increasing apoptosis in infected cells showing a viral-induced dependence on glycolysis. In contrast, pharmaceutical inhibition of PPAR or FXR reversed HCV-induced ketogenesis, but increased viral replication demonstrating a unique host anti-viral response. Our results show that viral-induced changes to host metabolism can be detrimental to its lifecycle demonstrating a distinct biological complexity.
Publication Title
Nuclear receptors control pro-viral and antiviral metabolic responses to hepatitis C virus infection.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Our previous investigation indicated that high-virulence C. gattii (C. gattii TIMM 4097) tend to reside in the alveoli, whereas low-virulence C. gattii (C. gattii TIMM 4903) tend to be washed out from the alveoli and move into the central side of the respiratory system. To test this hypothesis, we performed microarray assay.
Publication Title
How histopathology can contribute to an understanding of defense mechanisms against cryptococci.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 230 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Identification of genes up-regulated in ALK-positive and EGFR/KRAS/ALK-negative lung adenocarcinomas.
Publication Title
Identification of genes upregulated in ALK-positive and EGFR/KRAS/ALK-negative lung adenocarcinomas.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
Here we report that Nono instead functions as a chromatin regulator cooperating with Erk to regulate mESC pluripotency. We demonstrate that Nono loss leads to robust self-renewing mESCs with enhanced expression of Nanog and Klf4, epigenome and transcriptome re-patterning to a “ground-like state” with global reduction of H3K27me3 and DNA methylation resembling the Erk inhibitor PD03 treated mESCs and 2i (both GSK and Erk kinase inhibitors)-induced “ground state”. Mechanistically, Nono and Erk co-bind at a subset of development-related, bivalent genes. Ablation of Nono compromises Erk activation and RNA polymerase II C-terminal Domain serine 5 phosphorylation, and while inactivation of Erk evicts Nono from chromatin, revealing reciprocal regulation. Furthermore, Nono loss results in a compromised activation of its target bivalent genes upon differentiation and the differentiation itself. These findings reveal an unanticipated role of Nono in collaborating with Erk signaling to regulate the integrity of bivalent domain and mESC pluripotency. Overall design: mRNA-seq of parental and Nono-KO mES cells
Publication Title
Nono, a Bivalent Domain Factor, Regulates Erk Signaling and Mouse Embryonic Stem Cell Pluripotency.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Ion Torrent Proton
Description
Recently there has been growing interest in the immunomodulatory effects of endogenous danger signals known as alarmins. In this study, we explore a new combination therapy of anti-CD4 depleting antibody with an alarmin, high mobility group nucleosome binding protein 1 (HMGN1). Extremely low dose of HMGN1 with anti-CD4 depleting antibody exerted robust anti-tumor effects in Colon26 subtaneous murine model. To understand transcriptomic differences of CD8+ T cells in the tumor-bearing mice after treated with anti-CD4 depleting antibody or combination therapy of HMGN1 with anti-CD4 depleting antibody, we performed CD8 T cell transcriptome analysis using 3'SAGE-seq and Ion Proton sequencer. Overall design: CD8+ T cells were purified from single cell suspension of each implanted mouse tumor by lineage sorting (CD45-CD11b-B220-CD49b-Ter119-CD4-CD8+) through FACSAria. CD8 T cell transcriptome analysis were generated by 3'SAGE-seq using Ion Proton sequencer.
Publication Title
Combined treatment with HMGN1 and anti-CD4 depleting antibody reverses T cell exhaustion and exerts robust anti-tumor effects in mice.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The source of aldosterone in 30 to 40 % of patients with primary hyperaldosteronism (PA) is unilateral aldosterone-producing adenoma (APA). The mechanisms causing elevated aldosterone production in APA are unknown. Herein, we examined expression of G-protein coupled receptors (GPCR) in APA and demonstrate that compared to normal adrenals there is a general elevation of certain GPCR in many APA and/or ectopic expression of GPCR in others. RNA samples from normal adrenals (n = 5), APAs (n = 10), and cortisol-producing adenomas (CPAs) (n=13) were used on 15 genomic expression arrays, each of which included 223 GPCR transcripts presented in at least one out of 15 of the independent microarrays. The array results were confirmed using real-time RT-PCR (qPCR). Four GPCR transcripts exhibited a statistically significant increase that was greater than 3-fold compared to normal adrenals, suggesting a general increase in expression compared to normal adrenal glands. Four GPCR transcripts exhibited a greater than 15-fold increase of expression in one or more of the APA samples compared to normal adrenals. qPCR analysis confirmed array data and found the receptors with the highest fold increase in APA expression to be luteinizing hormone receptor (LH-R), serotonin receptor 4 (HTR4), gonadotropin-releasing hormone receptor (GnRHR), glutamate receptor metabotropic 3 (GRM3), endothelin receptor type B-like protein (GPR37), and ACTH receptor (MC2R). There are also sporadic increased expressions of these genes in the CPAs. Together, these findings suggest a potential role of altered GPCR expression in many cases of PA and provide candidate GPCR for further study.
Publication Title
G-protein-coupled receptors in aldosterone-producing adenomas: a potential cause of hyperaldosteronism.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina Genome Analyzer II
Description
We conditionally inactivated mouse Cdx2, a dominant regulator of intestinal development, and mapped its genome occupancy in adult intestinal villi. Although homeotic transformation, observed in Cdx2-null embryos, was absent in mutant adults, gene expression and cell morphology were vitally compromised. Lethality was accelerated in mice lacking both Cdx2 and its homolog Cdx1, with exaggeration of defects in crypt cell replication and enterocyte differentiation. Cdx2 occupancy correlated with hundreds of transcripts that fell but not with equal numbers that rose with Cdx loss, indicating a predominantly activating role at intestinal cis-regulatory regions. Integrated consideration of a mutant phenotype and cistrome hence reveals the continued and distinct requirement in adults of a master developmental regulator that activates tissue-specific genes.
Publication Title
Essential and redundant functions of caudal family proteins in activating adult intestinal genes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens, Trypanosoma cruzi
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
As Trypanosoma cruzi, the etiological agent of Chagas disease, multiplies in the cytoplasm of nucleated host cells, infection with this parasite is highly likely to affect host cells. We performed an exhaustive transcriptome analysis of T. cruzi-infected HeLa cells using an oligonucleotide microarray containing probes for greater than 47,000 human gene transcripts. In comparison with uninfected cells, those infected with T. cruzi showed greater than threefold up-regulation of 41 genes and greater than threefold down-regulation of 23 genes. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) of selected, differentially expressed genes confirmed the microarray data. Many of these up- and down-regulated genes were related to cellular proliferation, including seven up-regulated genes encoding proliferation inhibitors and three down-regulated genes encoding proliferation promoters, strongly suggesting that T. cruzi infection inhibits host cell proliferation, which may allow more time for T. cruzi to replicate and produce its intracellular nests. These findings provide new insight into the molecular mechanisms by which intracellular T. cruzi infection influences the host cell, leading to pathogenicity.
Publication Title
Transcriptome profile of Trypanosoma cruzi-infected cells: simultaneous up- and down-regulation of proliferation inhibitors and promoters.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Histone H3.3 is a highly conserved histone H3 replacement variant in metazoans, and has been implicated in many important biological processes including cell differentiation and reprogramming. Germline and somatic mutations in H3.3 genomic incorporation pathway components, or in H3.3 encoding genes, have been associated with human congenital diseases and cancers, respectively. However, the role of H3.3 in mammalian development remains unclear. To address this question, we generated H3.3 null mouse models through classical genetic approaches. We found H3.3 plays an essential role in mouse development. Complete depletion of H3.3 leads to developmental retardation and early embryonic lethality. At the cellular level, H3.3 loss triggers cell cycle suppression and cell death. Surprisingly, H3.3 depletion does not dramatically disrupt gene regulation in the developing embryo. Instead, H3.3 depletion causes dysfunction of heterochromatin structures at telomeres, centromeres and pericentromeric regions of chromosomes leading to mitotic defects. The resulting karyotypical abnormalities and DNA damage lead to p53 pathway activation. In summary, our results reveal that an important function of H3.3 is to support chromosomal heterochromatic structures, thus maintaining genome integrity during mammalian development. Overall design: RNA-seq in embryos at E10.5 comparing 3 samples with the following genotype Trp53-/-; H3f3afl/-; H3f3bfl/-; Sox2-CreTg/0 to three samples with the following genotype Trp53-/-; H3f3afl/+; H3f3bfl/+; Sox2-CreTg/0
Publication Title
Histone H3.3 maintains genome integrity during mammalian development.
Sample Metadata Fields
No sample metadata fields
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