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GSE54293
Homo sapiens
8 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
The influenza A(H1N1)pdm09 virus caused a global flu pandemic in 2009 and contributes to seasonal epidemics. Different treatment and prevention options for influenza have been developed and applied with limited success. Here we report that an Akt inhibitor MK2206 possesses potent antiviral activity against influenza A(H1N1)pdm09 virus in vitro. We showed that MK2206 blocks the entry of different A(H1N1)pdm09 strains into cells. Moreover, MK2206 prevented A(H1N1)pdm09-mediated activation of cellular signaling pathways and the development of cellular immune responses. Importantly, A(H1N1)pdm09 virus was unable to develop resistance to MK2206. Thus, MK2206 is a potent anti-influenza A(H1N1)pdm09 agent.
Publication Title
Akt inhibitor MK2206 prevents influenza pH1N1 virus infection in vitro.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The transcriptional coactivator ANGUSTIFOLIA 3 (AN3) stimulates cell proliferation during Arabidopsis leaf development, but the molecular mechanism is largely unknown. We show here that inducible nuclear localization of AN3 during initial leaf growth results in differential expression of important transcriptional regulators, including GROWTH REGULATING FACTORs (GRFs). Chromatin purification further revealed the presence of AN3 at the loci of GRF5, GRF6, CYTOKININ RESPONSE FACTOR 2 (CRF2), CONSTANS-LIKE 5 (COL5), HECATE 1 (HEC1), and ARABIDOPSIS RESPONSE REGULATOR 4 (ARR4). Tandem affinity purification of protein complexes using AN3 as bait identified plant SWITCH/SUCROSE NONFERMENTING (SWI/SNF) chromatin remodeling complexes formed around the ATPases BRAHMA (BRM) or SPLAYED (SYD). Moreover, SWI/SNF ASSOCIATED PROTEIN 73B (SWP73B) is recruited by AN3 to the promoter of GRF5, GRF3, COL5, and ARR4, and both SWP73B and BRM occupy the HEC1 promoter. Furthermore, we show that AN3 and BRM genetically interact. The data indicate that AN3 associates with chromatin remodelers to regulate transcription. In addition, modification of SWI3C expression levels increases leaf size, underlining the importance of chromatin dynamics for growth regulation. Our results place the SWI/SNF-AN3 module as a major player at the transition from cell proliferation to cell differentiation in a developing leaf.
Publication Title
ANGUSTIFOLIA3 binds to SWI/SNF chromatin remodeling complexes to regulate transcription during Arabidopsis leaf development.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219), Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Interleukin-6 (IL-6) is an important growth factor for estrogen receptor-alpha (ER) positive breast cancer, and elevated serum IL-6 is associated with poor prognosis. We firstly demonstrated that pSTAT3 is the primary downstream IL-6 signaling pathway in ER-positive breast cancer, using ten different breast cancer cell lines. Three-dimensional cultures of these cell lines were also used to develop a 17-gene IL-6 specific gene signature that could be used to identify IL-6 driven disease. This signature included a variety of genes involved in immune cell function and migration, cell growth and apoptosis, and the tumor microenvironment. To further validate this IL-6 signature, we obtained 36 human ER-positive breast cancer tumor samples with matched serum for gene expression profiling and determination of an IL-6 pathway activation score (PAS). Patients with high IL-6 PAS were also enriched for elevated serum IL-6 (>=10 pg/ml). We then utilized a murine MCF-7 xenograft model to determine the role of IL-6 in ER-positive breast cancer and potential anti-IL-6 therapy in vivo. When IL-6 was administered in vivo, MCF-7 cells engrafted without the need for estrogen supplementation. Subsequently, we prophylactically treated mice at MCF-7 engraftment with an anti-IL-6 antibody (siltuximab), fulvestrant or combination therapy. Siltuximab alone was able to blunt MCF-7 engraftment. Similarly, when tumors were allowed to grow to 125 mm3 before treatment, siltuximab alone demonstrated tumor regressions in 90% (9/10) of tumors. Given the established role for IL-6 in ER+ breast cancer, this data demonstrates the potential for anti-IL-6 therapeutics.
Publication Title
Interleukin-6 is a potential therapeutic target in interleukin-6 dependent, estrogen receptor-α-positive breast cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This study compares directed cardiac differentiation time-courses using (i) HuES6 cells with endogenous ISL1 knockout + inducible ISL1 transgene, and (ii) wild-type HuES6 cells.
Publication Title
Revised roles of ISL1 in a hES cell-based model of human heart chamber specification.
Sample Metadata Fields
Specimen part, Time
View Samples- Escherichia coli
- 12 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
We measured transcriptional changes resulting from overexpression or downregulation of the GTPase Obg.
Publication Title
Obg and Membrane Depolarization Are Part of a Microbial Bet-Hedging Strategy that Leads to Antibiotic Tolerance.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 50 Downloadable Samples
Illumina HiSeq 2500
Description
Transcriptome of S. cerevisiae in shifts between glucose and maltose media with different re-growth conditions Overall design: Cells are pregrown in maltose, then grown for different durations in glucose and then washed back to maltose
Publication Title
A new protocol for single-cell RNA-seq reveals stochastic gene expression during lag phase in budding yeast.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina mouse-6 v1.1 expression beadchip
Description
The atrioventricular (AV) node is a recurrent source of potentially life-threatening arrhythmias. Nevertheless, limited data are available on its developmental control or molecular phenotype. We used a novel AV node-specific reporter mouse to gain insight into the gene programs determining the formation and phenotype of the AV node. In the transgenic reporter, green fluorescent protein (GFP) expression was driven by 160 kbp of Tbx3 and flanking sequences. GFP was selectively expressed in the AV canal of embryos, and in the AV node of adults, while all other Tbx3+ conduction system components, including the AV bundle, were devoid of GFP expression. Fluorescent AV nodal (Tbx3BAC-Egfp) and complementary working (NppaBAC336-Egfp) myocardial cell populations of E10.5 embryos and E17.5 fetuses were purified using fluorescence-activated cell sorting, and their expression profiles were assessed by microarray analysis. We constructed a comprehensive list of sodium, calcium, and potassium channels specific for the nodal or working myocard. Furthermore, the data revealed that the AV node and the working myocardium phenotypes diverge during development, but that the functional gene classes characteristic for both compartments are maintained. Interestingly, the AV node-specific gene repertoire consisted of multiple neurotrophic factors not yet appreciated to play a role in nodal development. These data present the first genome-wide transcription profiles of the AV node during development, providing valuable information concerning its molecular identity.
Publication Title
Gene expression profiling of the forming atrioventricular node using a novel tbx3-based node-specific transgenic reporter.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Somatic ribosomal protein defects have recently been described in cancer, yet their impact on cellular transcription and translation remain poorly understood. Here we integrated mRNA sequencing, ribosome footprinting, polysomal RNA seq and quantitative mass spectrometry datasets obtained from an isogenic mouse lymphoid cell model in order to study the T-cell acute lymphoblastic leukemia (T-ALL) associated R98S mutation in ribosomal protein L10 (RPL10 R98S). RPL10 R98S induced changes in protein levels were to a much larger extent caused by transcriptional then translational changes and RPL10 R98S cells showed a gene signature corresponding to deregulation of hematopoietic transcription factors. Phosphoserine phosphatase (PSPH), a key enzyme in serine biosynthesis, displayed elevated transcription and translation and was one of the proteins showing the strongest upregulation in RPL10 R98S cells. Increased Psph protein levels were confirmed in RPL10 R98S engineered JURKAT cells and in hematopoietic cell cultures derived from Rpl10 R98S knock-in mice. Moreover, elevated serine and glycine biosynthesis in RPL10 R98S cells was supported by metabolic flux analyses. Analysis of PSPH expression levels in T-ALL patient samples revealed that PSPH upregulation is a generalized phenomenon in this disease, associated with elevated circulating serine and glycine levels. Addition of serine and glycine enhanced survival of stromal and myeloid cells, suggesting supportive effects on the hematopoietic niche. Finally, reduction of PSPH expression levels in T-ALL cell lines suppressed their in vitro proliferation and their capacity to expand in T-ALL xenograft models. In conclusion, transcriptome, translatome and proteome analysis of the RPL10 R98S mutation identified RPL10 R98S driven induction of cellular serine biosynthesis. Whereas serine metabolism has been implicated in cancer via PHGDH amplification, this is the first report supporting dependence of ALL cells on the serine biosynthesis enzyme PSPH. Overall design: 3 biological replicates for each condition (RPL10 R98S, RPL10 WT)
Publication Title
Translatome analysis reveals altered serine and glycine metabolism in T-cell acute lymphoblastic leukemia cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 193 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Microarrays were used to analyze the gene expression in endoscopic-derived intestinal mucosal biopsies from patients with inflammatory bowel diseas (IBD) and controls
Publication Title
Genetic and Transcriptomic Bases of Intestinal Epithelial Barrier Dysfunction in Inflammatory Bowel Disease.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hypoxia is a low oxygen condition that occurs in the developing tumor mass and that is associated with poor prognosis and resistance to chemo- and radio-therapy. The definition of the hypoxia gene signature is fundamental for the understanding of tumor biology, as in the case of neuroblastoma, the most common pediatric solid tumor. The issue of identifying a significant group of variables in microarray gene expression experiments is particularly difficult due to the typical high dimensional nature of the data and great effort has been spent in the development of feature selection techniques.
Publication Title
A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients.
Sample Metadata Fields
Cell line
View Samples