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E-MTAB-912
Saccharomyces cerevisiae
4 Downloadable Samples
Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extends the lifespan of various model organisms including yeast, flies and worms. In ageing yeast, spermidine treatment triggeres epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), leading to induction of autophagy and thereby suppressing oxidative stress and necrosis. In order to further characterize the effects by spermidine supplementation of aging yeast cultures and to understand how global histone deacetylation affects gene transcription during aging, Affymetrix-based microarray analyses of three day old as well as ten day old cultures with and without administration of spermidine was performed.
Publication Title
Induction of autophagy by spermidine promotes longevity.
Sample Metadata Fields
Age, Compound, Time
View Samples- Mus musculus, Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We examined global gene expression patterns in response to PGC-1 expression in cells derived from liver or muscle.
Publication Title
Direct link between metabolic regulation and the heat-shock response through the transcriptional regulator PGC-1α.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Cell adhesion plays an important role in determining cell shape and function in a variety of physiological and pathophysiological conditions. While links between metabolism and cell adhesion were previously suggested, the exact context and molecular details of such a cross-talk remain incompletely understood.
Publication Title
Inhibition of Adhesion Molecule Gene Expression and Cell Adhesion by the Metabolic Regulator PGC-1α.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Secreted proteins serve pivotal roles in the development of multicellular organisms, acting as structural matrix, extracellular enzymes and signal molecules. In this study we demonstrate, unexpectedly, that PGC-1, a critical transcriptional co-activator of metabolic gene expression, functions to down-regulate expression of diverse genes encoding secreted molecules and extracellular matrix (ECM) components to modulate the secretome. We show that both endogenous and exogenous PGC-1 down-regulate expression of numerous genes encoding secreted molecules. Mechanistically, results obtained using mRNA stability measurements as well as intronic RNA expression analysis are consistent with a transcriptional effect of PGC-1 on expression of genes encoding secreted proteins. Interestingly, PGC-1 requires the central heat shock response regulator HSF1 to affect some of its targets, and both factors co-reside on several target genes encoding secreted molecules in cells. Finally, using a mass spectrometric analysis of secreted proteins, we demonstrate that PGC-1 modulates the secretome of mouse embryonic fibroblasts (MEFs).
Publication Title
Control of Secreted Protein Gene Expression and the Mammalian Secretome by the Metabolic Regulator PGC-1α.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 8 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
The aim of this transcription profiling study was to identify novel genes that could be used to distinguish bovine Nucleus pulposus (NP) cells from articular cartilage (AC) and annulus fibrosus (AF) cells and to further determine their expression in normal and degenerate human intervertebral disc (IVD). This study has identified a number of novel genes that characterise the bovine and human NP and IVD cell phenotypes and allows for discrimination between AC, AF and NP cells.<br></br><br></br>
Publication Title
Transcriptional profiling of bovine intervertebral disc cells: implications for identification of normal and degenerate human intervertebral disc cell phenotypes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 54 Downloadable Samples
Illumina HiSeq 2000
Description
The catalytic activities of covalent and ATP-dependent chromatin remodeling are central to regulating the conformational state of chromatin and the resultant transcriptional output. The enzymes that catalyze these activities are often contained within multiprotein complexes in nature. Two such multiprotein complexes, the polycomb repressive complex 2 (PRC2) methyltransferase and the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeler have been reported to act in opposition to each other during development and homeostasis. An imbalance in their activities induced by mutations/deletions in complex members (e.g. SMARCB1) has been suggested to be a pathogenic mechanism in certain human cancers. Here we show that preclinical models of synovial sarcoma - a cancer characterized by functional SMARCB1 loss via its displacement from the SWI/SNF complex through the pathognomonic SS18-SSX fusion protein - display sensitivity to pharmacologic inhibition of EZH2, the catalytic subunit of PRC2. Treatment with tazemetostat, a clinical-stage, selective and orally bioavailable small-molecule inhibitor of EZH2 enzymatic activity reverses a subset of synovial sarcoma gene expression and results in concentration-dependent cell growth inhibition and cell death specifically in SS18-SSX fusion-positive cells in vitro. Treatment of mice bearing either a cell line or two patient-derived xenograft models of synovial sarcoma leads to dose-dependent tumor growth inhibition with correlative inhibition of trimethylation levels of the EZH2-specific substrate, lysine 27 on histone H3. These data demonstrate a dependency of SS18-SSX-positive, SMARCB1-deficient synovial sarcomas on EZH2 enzymatic activity and suggests the potential utility of EZH2-targeted drugs in these genetically defined cancers. Overall design: Three different in vivo models of synovial sarcoma (xenograft: Fuji; PDX: CTG-0331 and CTG-0771) treated with or without the indicated dose of the EZH2 inhibitor, tazemetostat
Publication Title
Preclinical Evidence of Anti-Tumor Activity Induced by EZH2 Inhibition in Human Models of Synovial Sarcoma.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
NPTX1 is a key inducer of neural lineages from the human ESC.
Publication Title
NPTX1 regulates neural lineage specification from human pluripotent stem cells.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2500
Description
Group 2 innate lymphoid cells (ILC2) are tissue-resident innate lymphocytes that are derived from common lymphoid progenitor (CLP). While specific progenitors and transcription factors essential for ILC2 differentiation have been well studied, external factors that regulate the commitment from CLP to ILC lineage, site that promote ILC2 terminal differentiation, and stromal cells that provide optimal microenvironment for ILC2 specific development are not fully understood. we demonstrated that the three key external factors such as concentration of IL-7 and the strength and duration of Notch signaling conditionally determined the fate of CLP toward T cell, B cell, or ILC lineages, which seems to be an important process from CLP to CHILP differentiation in the fetal liver. Furthermore, we identified ILC progenitors lacking the developmental potential to become T or B cells, and KLRG1- immature ILC2 that require STAT5 for functional maturation in the mesentery. We also identified PDGFRa+gp38+ mesenchymal cells in the mesentery that support ILC2 differentiation from ILC progenitors but not from CLP. Finally, single-cell RNA-sequencing (scRNA-seq) analysis of mesenteric cells demonstrated that PDGFRa+gp38+ cells are heterogeneous populations. Collectively, our result suggested that early differentiation of ILC2 occurs in the primary lymphoid organ with regulation of environmental factors, and final differentiation occurs in the peripheral tissues once after CHILP migrate into the periphery. Overall design: Duplicate samples (mouse 1 and mouse 2) were processed for single cell-based RNA sequencing with Illumina HiSeq 2500 with 50 paired-end reads, using barcorded RNA library.
Publication Title
Peripheral PDGFRα<sup>+</sup>gp38<sup>+</sup> mesenchymal cells support the differentiation of fetal liver-derived ILC2.
Sample Metadata Fields
Sex, Cell line, Subject
View Samples- Saccharomyces cerevisiae
- 66 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The SAGA co-activator has been implicated in the regulation of a smal subset of genes in budding yeast in transcriptomic analyses performed in steady-state levels of RNA.
Publication Title
SAGA Is a General Cofactor for RNA Polymerase II Transcription.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Clinical score and transcript abundance patterns identify Kawasaki disease patients who may benefit from addition of methylprednisolone.
Publication Title
Clinical score and transcript abundance patterns identify Kawasaki disease patients who may benefit from addition of methylprednisolone.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples