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GSE22299
Rattus norvegicus
50 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
A delay in the mammalian inflammatory response is a prominent feature of infection with Yersinia pestis, the agent of bubonic and pneumonic plague. Y. pestis factors have been identified that either do not stimulate a normal inflammatory response, or actively suppress it. Prominent among these are components of the Type III secretion system that is encoded on the Yersinia virulence plasmid (pYV). We used a rat model of bubonic plague to characterize the kinetics and extent of the mammalian transcriptomic response to infection with wild-type or pYV-negative Y. pestis in the draining lymph node. Remarkably, dissemination and multiplication of wild-type Y. pestis during the bubonic stage of disease did not induce any detectable gene expression response by host lymph node cells. This was followed, however, by an extensive transcriptomic response, including upregulation of several cytokine, chemokine, and other immune response genes, after systemic spread during septicemic plague. Matched lymph node samples used for histopathology and extracellular cytokine measurements, combined with the microarray data set, broadly outlined the mammalian immune response to Y. pestis and how it is influenced by pYV-encoded factors. The results indicate that both WT and pYV Y. pestis induce primarily a Th17 response, and not a Th1 or Th2 response. In the absence of pYV, a sustained recruitment of polymorphonuclear leukocytes, the major Th17 effector cell, to the lymph node resulted in clearance of infection. Thus, the ability to counteract a Th17- driven PMN response in the lymph node appears to be a major function of the Y. pestis virulence plasmid. In contrast, classic markers of the proinflammatory response and macrophage activation, such as TNF- and IFN-, were not induced at all by pYV Y. pestis, and appeared only late in infection with WT Y. pestis.
Publication Title
Transcriptomic and innate immune responses to Yersinia pestis in the lymph node during bubonic plague.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 21 Downloadable Samples
IlluminaHiSeq2000
Description
Aberrant expression of cancer genes and non-canonical RNA species is a hallmark of cancer. However, the mechanisms driving such atypical gene expression programs are incompletely understood. Here, our transcriptional profiling of a cohort of 50 primary clear cell renal cell carcinoma (ccRCC) samples from The Cancer Genome Atlas (TCGA) reveals that transcription read-through beyond the termination site is a source of transcriptome diversity in cancer cells. Amongst the genes most frequently mutated in ccRCC, we identified SETD2 inactivation as a potent enhancer of transcription read-through. We further show that invasion of neighbouring genes and generation of RNA chimeras are functional outcomes of transcription read-through. We identified the BCL2 oncogene as one of such invaded genes and detected a novel chimera, the CTSC-RAB38, in 20% of ccRCC samples. Collectively, our data highlight a novel link between transcription read-through and aberrant expression of oncogenes and chimeric transcripts that is prevalent in cancer. Overall design: RNA-seq of SETD2 mutant and wild-type ccRCC cell lines.
Publication Title
Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The steroid hormone aldosterone plays a role in vascular function and disease. Aldosterone activates the mineralocorticoid receptor (MR), a ligand-activated transcription factor. MR have been found to be expressed in vascular cells and vessels.
Publication Title
Placental growth factor mediates aldosterone-dependent vascular injury in mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Background and aims: There are considerable evidences demonstrating that angiogenesis and chronic inflammation are mutually dependent. However, although cirrhosis progression is characterized with a chronic hepatic inflammatory process, this connection is not sufficiently explored as a therapeutic strategy. Therefore, this study was aimed to assess the potential benefits of targeting angiogenesis in cirrhotic livers to modulate inflammation and fibrosis. For this purpose, we evaluate the therapeutic utility of angiogenesis inhibitors. Methods: The in vivo effects of angiogenesis inhibitors were monitored in liver of cirrhotic rats by measuring angiogenesis, inflammatory infiltrate, fibrosis, a-smooth muscle actin (a-SMA) accumulation, differential gene expression (by microarrays), and portal pressure. Results: Cirrhosis progression was associated with a significant enhancement of vascular density and expression of vascular endothelial growth factor-A (VEGF-A), angiopoietin-1, angiopoietin-2 and placental growth factor (PlGF) in cirrhotic livers. The newly formed hepatic vasculature expressed vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Interestingly, the expression of these adhesion molecules correlated well with local inflammatory infiltrate. Livers of cirrhotic rats treated with angiogenesis inhibitors presented a significant decrease in hepatic vascular density, inflammatory infiltrate, a-SMA abundance, collagen expression and portal pressure. Conclusion: Angiogenesis inhibitors may offer a potential novel therapy for cirrhosis due to its multiple mechanisms of action against angiogenesis, inflammation and fibrosis in cirrhotic livers.
Publication Title
Antiangiogenic treatment with sunitinib ameliorates inflammatory infiltrate, fibrosis, and portal pressure in cirrhotic rats.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Methods of reprogramming somatic cells to an induced pluripotent state (iPSC) have enabled the direct modeling of human disease and ultimately promise to revolutionize regenerative medicine. iPSCs offer an invaluable source of patient-specific pluripotent stem cells for disease modeling, drug screening, toxicology tests and importantly for regenerative medicine, and already have been employed to unmask novel insights into human diseases. While iPSCs can be consistently generated through overexpression of the four Yamanaka Factors OCT4, SOX2, KLF4 and c-MYC (OSKM), reprogrammed cells present worrisome differences with embryonic stem cells in transcriptional and epigenetic profiles, as well as developmental potential and difficulties in cell culturing. A thorough mechanistic understanding of the reprogramming process is critical to overcoming these barriers to the clinical use of iPSC. We have recently published a novel factor combination based on molecules specifically enriched in the metaphase II human oocyte. We have shown that just the overexpression of histone-remodeling chaperone ASF1A and OCT4 in hADFs previously exposed to the oocyte-specific paracrine growth factor GDF9 can reprogram hADFs into pluripotent cells (AO9-iPSCs). Our study contributes to the understanding of the molecular pathways governing somatic cell reprogramming. Here we want to go deeper in the reprogramming mechanisms by understanding the importance of somatic cell origin, and analyzing (and establishing comparison with) the transcriptional and epigenetic characteristics of AO9-iPSCs. As the intrinsic histone chaperone activity of ASF1A and our data indicate, these cells could be closer to the embryonic pluripotent state, with less epigenetic memory, better culture properties and differentiation potential.
Publication Title
Analysis of Menstrual Blood Stromal Cells Reveals SOX15 Triggers Oocyte-Based Human Cell Reprogramming.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Our lab established the M0505 cell line from the ovarian surface epithelium (OSE) of FVB/N mice in May 2005 in order to study OSE biology. This cell line spontaneously transformed into the spontaneously transformed OSE (STOSE) cell line in mid 2012.
Publication Title
A new spontaneously transformed syngeneic model of high-grade serous ovarian cancer with a tumor-initiating cell population.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
U2AF65 is an essential splicing factor involved in the 3'splice site recognition dureing the first steps of spliceosome assembly. In addition, this protein has nucleocytoplasmic shuttling activity and the Drosophila homologue has been implicated in mRNA export.
Publication Title
Genome-wide identification of functionally distinct subsets of cellular mRNAs associated with two nucleocytoplasmic-shuttling mammalian splicing factors.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
PTB is multifunctional RNA binding protein reported to be involved in splicing, 3' -end processing, stability and translational regulation.
Publication Title
Genome-wide identification of functionally distinct subsets of cellular mRNAs associated with two nucleocytoplasmic-shuttling mammalian splicing factors.
Sample Metadata Fields
No sample metadata fields
View Samples- Macaca fascicularis
- 222 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Relatively little is understood about the dynamics of global hostpathogen transcriptome changes that occur during bacterial infection of mucosal surfaces. To test the hypothesis that group A Streptococcus (GAS) infection of the oropharynx provokes a host transcriptome response, we performed genome-wide transcriptome analysis using a nonhuman primate model of experimental pharyngitis. We also identified host and pathogen biological processes and individual host and pathogen gene pairs with correlated patterns of expression, suggesting interaction. For this study, 509 host genes and seven biological pathways were differentially expressed throughout the entire 32-day infection cycle. GAS infection produced an initial widespread significant decrease in expression of many host genes, including those involved in cytokine production, vesicle formation, metabolism, and signal transduction. This repression lasted until day 4, at which time a large increase in expression of host genes was observed, including those involved in protein translation, antigen presentation, and GTP-mediated signaling. The interactome analysis identified 73 host and pathogen gene pairs with correlated expression levels. We discovered significant correlations between transcripts of GAS genes involved in hyaluronic capsule production and host endocytic vesicle formation, GAS GTPases and host fibrinolytic genes, and GAS response to interaction with neutrophils. We also identified a strong signal, suggesting interaction between host T cells and genes in the GAS mevalonic acid synthesis pathway responsible for production of isopentenyl-pyrophosphate, a short-chain phospholipid that stimulates these T cells. Taken together, our Q:2 results are unique in providing a comprehensive understanding of the hostpathogen interactome during mucosal infection by a bacterial pathogen.
Publication Title
Interactome analysis of longitudinal pharyngeal infection of cynomolgus macaques by group A Streptococcus.
Sample Metadata Fields
Sex, Subject
View Samples- Homo sapiens
- 94 Downloadable Samples
- Illumina HiSeq 4000, Illumina HiSeq 2500
Description
Numerous long intervening non-coding RNA (lincRNA) are generated from the mammalian genome by RNA polymerase II (Pol II) transcription. Although multiple functions have been ascribed to lincRNA, their synthesis and turnover remain poorly characterised. Here we define systematic differences in transcription and RNA processing between protein-coding and lincRNA genes in human HeLa cells. This is based on a range of nascent transcriptomic approaches applied to different nuclear fractions, including mammalian native elongating transcript sequencing (mNET-seq). Notably mNET-seq patterns specific for different Pol II CTD phosphorylation states reveal weak co-transcriptional splicing and poly(A) signal independent Pol II termination on lincRNA as compared to pre-mRNA. In addition, lincRNA are mostly restricted to chromatin where they are co-transcriptionally degraded by the RNA exosome. We also show that a lincRNA specific co-transcriptional RNA cleavage mechanism acts to induce premature termination. In effect functional lincRNA must escape from this targeted nuclear surveillance process. Overall design: We employed CTD phospho specific mNET-Seq with pla-B splicing inhibitor and RNA processing factors knockdown (DGCR8, Dicer1, EXOSC3 and CPSF73 proteins). mNET-seq experiments with 1% Empigen detergent treatment were performed to separate Pol II-associated complex from Pol II. We also analyzed subcellur RNA and pA+ and pA- nucleoplasm RNA libraries for RNA processing efficiency and the turnover. There are 4 raw files come from an illumina experiment (per sample), produced in 2 lanes. They were all mapped together.
Publication Title
Distinctive Patterns of Transcription and RNA Processing for Human lincRNAs.
Sample Metadata Fields
Cell line, Subject
View Samples