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GSE100928
Homo sapiens
30 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Type I interferons (IFN) are important components of the innate antiviral response. A key signalling pathway activated by IFNa is the Janus kinase signal transducer and activator of transcription (JAKSTAT) pathway. Major components of the pathway have been identified. However, critical kinetic properties that facilitate accelerated initiation of intracellular antiviral signalling and thereby promote virus elimination remain to be determined. By combining mathematical modelling with experimental analysis, we show that control of dynamic behaviour is not distributed among several pathway components but can be primarily attributed to interferon regulatory factor 9 (IRF9), constituting a positive feedback loop. Model simulations revealed that increasing the initial IRF9 concentration reduced the time to peak, increased the amplitude and enhanced termina- tion of pathway activation. These model predictions were experimentally verified by IRF9 over-expression studies. Furthermore, acceleration of signal processing was linked to more rapid and enhanced expression of IFNa target genes. Thus, the amount of cellular IRF9 is a crucial determinant for amplification of early dynamics of IFNa-mediated signal transduction.
Publication Title
Combining theoretical analysis and experimental data generation reveals IRF9 as a crucial factor for accelerating interferon α-induced early antiviral signalling.
Sample Metadata Fields
Specimen part, Disease, Cell line, Time
View Samples- Mus musculus
- 19 Downloadable Samples
Illumina HiSeq 2500
Description
RNA was purified from lung tissue and isolated Alveolar type II cells. The "SAMPLE_ID" sample description is a sample identifier internal to Genentech. The ID of this project in Genentech''s ExpressionPlot database is PRJ0007671 Overall design: RNA from lung and Alveolar type II cells of the following mutant mice: (1) SpcCreERT2;RosatdTomato n=5 ; (2) SpcCreERT2;RosatdTomato;Etv5ko/loxp n= 5
Publication Title
Transcription factor Etv5 is essential for the maintenance of alveolar type II cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA was purified from lung tissue and isolated Alveolar type II cells. The "SAMPLE_ID" sample description is a sample identifier internal to Genentech. The ID of this project in Genentech''s ExpressionPlot database is PRJ0005064 Overall design: RNA from lung and Alveolar type II cells of the following mutant mice: (1) KRaswt/d12;RosaCreERT2 n=4 (2) KRaswt/d12; Etv5loxp/loxp;RosaCreERT2 n=4 (3) KRaswt/d12; Etv4KO/KO; Etv5loxp/loxp;RosaCreERT2 n=4
Publication Title
Transcription factor Etv5 is essential for the maintenance of alveolar type II cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Identify genes which are differentially expressed in ?Cop1ß compared to control islets and are also signficantly rescued in ?Cop1? ?ETV1/4/5ß Overall design: Islets were harvested from 5 biological replicates of the followig genotypes: Control, ?Cop1ß and ?Cop1? ?ETV1/4/5ß. Islets were individually handpicked and total RNA was isolated and purified for library preperation and Next Generation Sequencing.
Publication Title
β-Cell Insulin Secretion Requires the Ubiquitin Ligase COP1.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Myeloid dendritic cells (DC) and macrophages play an important role in pathogen sensing and antimicrobial defense. Recently we demonstrated that infection of human DC with intracellular bacterium Listeria monocytogenes (L.monocytogenes) leads to the induction of the immunoinhibitory enzyme indoleamine 2,3-dioxygenase (Popov et al., J Clin Invest, 2006), while in the previous studies L.monocytogenes infection was associated with a rather stimulatory DC phenotype. To clarify this discrepancy we performed comparative microarray analysis of immature mo-DC (immDC), mature stimulatory mo-DC (matDC) and mature inhibitory DC either stimulated with prostaglandin E2 (PGE2-DC) or infected with L.monocytogenes (infDC). Studying infection of human myeloid DC with Listeria monocytogenes, we found out, that infected DC are modified by the pathogen to express multiple inhibitory molecules, including indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2, interleukin 10 and CD25, which acts on DC as IL-2 scavenger. All these inhibitory molecules, expressed on regulatory DC (DCreg), are strictly TNF-dependent and are in concert suppressing T-cell responses. Moreover, only DCreg can efficiently control the number of intracellular listeria, mostly by IDO-mediated mechanisms and by other factors, remaining to be identified. Analyzing publicly acessible data of transcriptional changes in DC and macrophages, infected by various pathogens and parasites (GEO, GSE360), we noticed that infection of these cells with Mycobacterium tuberculosis causes transcriptional response, comparable with the one caused by listeria in human DC. In fact, granuloma in tuberculosis and listeriosis in vivo are enriched for myeloid DC and macrophages characterized by regulatory phenotype.
Publication Title
Infection of myeloid dendritic cells with Listeria monocytogenes leads to the suppression of T cell function by multiple inhibitory mechanisms.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Malignancies arising from mutation of tumor suppressor genes display an unexplained tissue proclivity. For example, tumor suppressor BAP1 encodes a ubiquitously expressed deubiquitinase for histone H2A but germline mutations predominantly cause uveal melanomas and mesotheliomas. We show that BAP1 inactivation causes apoptosis in mouse embryonic stem cells, fibroblasts, liver and pancreas, whereas melanocytes and mesothelial cells remain viable. E3 ligase RNF2, which silences genes by monoubiquitinating H2A, promoted apoptosis in BAP1-deficient cells by suppressing the pro-survival genes Bcl-2 and Mcl-1. Our data argue that BAP1 modulates gene expression by countering H2A ubiquitination, but its loss only promotes tumorigenesis in cells that do not engage an RNF2-dependent apoptotic program. We propose that intolerance of BAP1 loss, and perhaps the loss of other tumor suppressors, restricts the mutant tumor spectrum. Overall design: RNA was extracted from following genotypes - BAP1 wt (WT) and BAP1 knockout (BAP1 KO).
Publication Title
Intrinsic apoptosis shapes the tumor spectrum linked to inactivation of the deubiquitinase BAP1.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HiSeq 2500
Description
The goals of this study are to compare NGS-derived whole transcriptome profiles (RNA-seq) of H5N1 infected A549 cells overexpressing either negative control mimic or miR-324-5p mimic Overall design: A549 cells were either mock transfected or transfected with either negative control or mir-324-5p mimic. After 12 hours cells were either mock infected (mock transfected cells) or infected with A/duck/India/02CA10/2011 - H5N1 virus (negative control and miR-324-5p overexpressing cells)
Publication Title
MicroRNA hsa-miR-324-5p Suppresses H5N1 Virus Replication by Targeting the Viral PB1 and Host CUEDC2.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 21 Downloadable Samples
- Illumina HiSeq 2500
Description
The prevailing dogma that approximately 50% of our genome is “junk” DNA composed of transposable elements and retroviral insertions has recently been challenged. It has become evident that our genome has taken advantage of these transposable elements and uses them as a source of DNA to generate novel genes, which subsequently allow the organism to evolve. This process is termed “domestication of transposable elements” and the majority of these genes have been found to be essential for the existence of the organism. One of these developmentally essential domesticated genes: Peg10 (paternally expressed gene 10), was derived from a Ty3/gyspy LTR retrotransposon, yet lost its ability to transpose due to mutational events during its domestication. Remarkably, Peg10 has successfully maintained its Gag and Pol-like domains for millions of years. Peg10 orthologues are expressed in eutherian mammals and are essential for placentogenesis. To address the functional mechanisms of Peg10 we studied it in Trophoblast Stem Cells (TSCs). We find that the Gag of Peg10 is fully active: it promotes budding of vesicles, akin to the viral counterpart that catalyzes the budding of viruses. TSCs, deleted for Peg10, fail to differentiate into placental lineages, underscoring a critical role in lineage specification. This paper discusses our efforts to characterize the contents of Peg10 vesicles and whether such vesicles regulate lineage specification. Overall design: RNA was extracted from following genotypes - wildtype TSCs (WT_TSC), Peg10 knockout TSCs (KO_TSC), wildtype TSCs differentiated in 20% oxygen (WT_TSC_diff), Peg10 knockout TSCs differentiated in 20% oxygen (KO_TSC_diff), wildtype TSCs differentiated in 2% oxygen (WT_diff_2O2),and Peg10 knockout TSCs differentiated in 2% oxygen (KO_diff_2O2). Cells are kept in the pluripotent state by growing them on CellStart/Fgf4/Heparin. The cells were differentiated in two different conditions: 20% oxygen and 2% oxygen. The samples were collected at 10th day following differentiation. Cells are harvested and RNA is isolated using the Qiagen RNeasy kit. RT-PCR was performed for several differentiation markers to validate the success of the assay.
Publication Title
The Gag protein PEG10 binds to RNA and regulates trophoblast stem cell lineage specification.
Sample Metadata Fields
Specimen part, Subject
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Analyses of expression differences in flower bud and leaf of scion and rootstock, in homografts of Arabidopsis
Publication Title
Grafting triggers differential responses between scion and rootstock.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 78 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rheumatoid arthritis (RA) is a complex and clinically heterogeneous autoimmune disease.
Publication Title
PILRα negatively regulates mouse inflammatory arthritis.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples