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GSE9590
Saccharomyces cerevisiae
12 Downloadable Samples
Affymetrix Yeast Genome S98 Array (ygs98)
Description
The irreversible decarboxylation step, which commits 2-oxo acids to the Ehrlich pathway, was initially attributed to pyruvate decarboxylase. However, the yeast genome was shown to harbour no fewer than 5 genes that show sequence similarity with thiamine-diphosphate dependent decarboxylase genes. Three of these (PDC1, PDC5 and PDC6) encode pyruvate decarboxylases { while ARO10 and THI3 represent alternative candidates for Ehrlich-pathway decarboxylases.
Publication Title
The Ehrlich pathway for fusel alcohol production: a century of research on Saccharomyces cerevisiae metabolism.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 1 Downloadable Sample
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Zinc is indispensable for the catalytic activity and structural stability of many proteins, and its deficiency can have severe consequences for microbial growth in natural and industrial environments. For example, Zn depletion in wort negatively affects beer fermentation and quality. Several studies have investigated yeast adaptation to low Zn supply, but were all performed in batch cultures, where specific growth rate depends on Zn availability. The transcriptional responses to growth-rate and Zn availability are then intertwined, which obscures result interpretation. In the present study, transcriptional responses of Saccharomyces cerevisiae to Zn availability were investigated at a fixed specific growth rate under Zn limitation and excess in chemostat culture. To investigate the context-dependency of this transcriptional response, yeast was grown under several chemostat regimes resulting in various carbon (glucose), nitrogen (ammonium) and oxygen supplies. A robust set of genes that responded consistently to Zn limitation was identified and enabled the definition of a Zn-specific Zap1 regulon comprising of 26 genes and characterized by a broader ZRE consensus (MHHAACCBYNMRGGT) than so far described. Most surprising was the Zn-dependent regulation of genes involved in storage carbohydrate metabolism. Their concerted down-regulation was physiologically relevant as revealed by a substantial decrease in glycogen and trehalose cellular content under Zn limitation. An unexpectedly large amount of genes were synergistically or antagonistically regulated by oxygen and Zn availability. This combinatorial regulation suggested a more prominent involvement of Zn in mitochondrial biogenesis and function than hitherto identified
Publication Title
Physiological and transcriptional responses of Saccharomyces cerevisiae to zinc limitation in chemostat cultures.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 5 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Zinc is indispensable for the catalytic activity and structural stability of many proteins, and its deficiency can have severe consequences for microbial growth in natural and industrial environments. For example, Zn depletion in wort negatively affects beer fermentation and quality. Several studies have investigated yeast adaptation to low Zn supply, but were all performed in batch cultures, where specific growth rate depends on Zn availability. The transcriptional responses to growth-rate and Zn availability are then intertwined, which obscures result interpretation. In the present study, transcriptional responses of Saccharomyces cerevisiae to Zn availability were investigated at a fixed specific growth rate under Zn limitation and excess in chemostat culture. To investigate the context-dependency of this transcriptional response, yeast was grown under several chemostat regimes resulting in various carbon (glucose), nitrogen (ammonium) and oxygen supplies. A robust set of genes that responded consistently to Zn limitation was identified and enabled the definition of a Zn-specific Zap1 regulon comprising of 26 genes and characterized by a broader ZRE consensus (MHHAACCBYNMRGGT) than so far described. Most surprising was the Zn-dependent regulation of genes involved in storage carbohydrate metabolism. Their concerted down-regulation was physiologically relevant as revealed by a substantial decrease in glycogen and trehalose cellular content under Zn limitation. An unexpectedly large amount of genes were synergistically or antagonistically regulated by oxygen and Zn availability. This combinatorial regulation suggested a more prominent involvement of Zn in mitochondrial biogenesis and function than hitherto identified.
Publication Title
Physiological and transcriptional responses of Saccharomyces cerevisiae to zinc limitation in chemostat cultures.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 3 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Zinc is indispensable for the catalytic activity and structural stability of many proteins, and its deficiency can have severe consequences for microbial growth in natural and industrial environments. For example, Zn depletion in wort negatively affects beer fermentation and quality. Several studies have investigated yeast adaptation to low Zn supply, but were all performed in batch cultures, where specific growth rate depends on Zn availability. The transcriptional responses to growth-rate and Zn availability are then intertwined, which obscures result interpretation. In the present study, transcriptional responses of Saccharomyces cerevisiae to Zn availability were investigated at a fixed specific growth rate under Zn limitation and excess in chemostat culture. To investigate the context-dependency of this transcriptional response, yeast was grown under several chemostat regimes resulting in various carbon (glucose), nitrogen (ammonium) and oxygen supplies. A robust set of genes that responded consistently to Zn limitation was identified and enabled the definition of a Zn-specific Zap1 regulon comprising of 26 genes and characterized by a broader ZRE consensus (MHHAACCBYNMRGGT) than so far described. Most surprising was the Zn-dependent regulation of genes involved in storage carbohydrate metabolism. Their concerted down-regulation was physiologically relevant as revealed by a substantial decrease in glycogen and trehalose cellular content under Zn limitation. An unexpectedly large amount of genes were synergistically or antagonistically regulated by oxygen and Zn availability. This combinatorial regulation suggested a more prominent involvement of Zn in mitochondrial biogenesis and function than hitherto identified
Publication Title
Physiological and transcriptional responses of Saccharomyces cerevisiae to zinc limitation in chemostat cultures.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 384 Downloadable Samples
Illumina HiSeq 2500
Description
Cellular dormancy and heterogeneous cell cycle lengths provide important explanations for treatment failure following adjuvant therapy with S-phase cytotoxics in colorectal cancer (CRC) yet the molecular control of the dormant versus cycling state remains unknown. In CRCs dormant cells are found to be highly clonogenic and resistant to chemotherapies. We sought to understand the molecular features of dormant CRC cells to facilitate rationale identification of compounds to target both dormant and cycling tumour cells. Overall design: Six colorectal cancer cell lines (DLD1, HCT15, HT55, SW948, RKO and SW48) were labelled with the cell permeable dye CFSE and then grown in non-adherent spheroid culture for 6 days to enable identification of dormant cells that retain CFSE (LRC) and cycling cells (BULK). LRCs and BULK populations were then FACS sorted from each cell line in quadruplicate. As a control experiment, to identify off-target effects of the CFSE dye and culture artefacts, BULK populations from DLD1 cells at d1 and d6 after seeding both with and without CFSE labelling were included in the RNAseq analysis. RNA was extracted using the RNAeasy Micro Plus kit (Qiagen) and quantified using the Qubit RNA Assay Kit (Thermo Fisher Scientific). RNA quality was assessed using the Agilent Bioanalyser system as per manufacturer's instructions. Following normalisation and sample randomisation, Truseq library (Illumina) preparation was carried out at the CRUK CI genomics facility and subsequent single end, 50bp sequencing using the HiSeq system (Illumina). Following human genome alignment (hg19), read counts were normalised and differential expression tested using the DEseq protocol.
Publication Title
Itraconazole targets cell cycle heterogeneity in colorectal cancer.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
Two cell lines (HT55 and SW948) were found responsive to itraconazole treatment. To identify the mode of action cells were treated with itraconazole or control (DMSO) and then subjected to RNAseq analysis once the phenotype had developed Overall design: HT55 and SW948 cells were seeded in adherent culture and treated with 5uM itraconazole or DMSO for 6 days. Cells then underwent RNA extraction using the RNAeasy Micro Plus kit (Qiagen) and quantified using the Qubit RNA Assay Kit (Thermo Fisher Scientific). RNA quality was assessed using the Agilent Bioanalyser system as per manufacturer's instructions. Following normalisation and sample randomisation, Truseq library (Illumina) preparation was carried out at the CRUK CI genomics facility and subsequent single end, 50bp sequencing using the HiSeq system (Illumina). Following human genome alignment (hg19), read counts were normalised and differential expression tested using the DEseq protocol.
Publication Title
Itraconazole targets cell cycle heterogeneity in colorectal cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Rattus norvegicus
- 23 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The area postrema (AP) is a sensory circumventricular organ characterised by extensive fenestrated vasculature and neurons which are capable of detecting circulating signals of osmotic, cardiovascular, immune and metabolic status. The AP can communicate these messages via efferent projections to brainstem and hypothalamic structures that are able to orchestrate an appropriate response. We have used microarrays to profile the transcriptome of the AP in the Sprague Dawley (SD) and Wistar Kyoto (WKY) rat and present here a comprehensive catalogue of gene expression, focussing specifically on the population of ion channels, receptors and G protein-coupled receptors (GPCRs) expressed in this sensory tissue; of the GPCRs expressed in the rat AP we identified ~36% that are orphans having no established ligand. We have also looked at the ways in which the AP transcriptome responds to the physiological stressors of 72-hours dehydration (DSD) and 48-hours fasting (FSD) and have performed microarrays under these conditions. Comparison between the DSD and SD or between FSD and SD revealed only a modest number of AP genes that are regulated by these homeostatic challenges. The expression levels of a much larger number of genes are altered in the spontaneously hypertensive rat (SHR) AP compared to the normotensive WKY controls however. Finally, analysis of these hypertension-related elements revealed genes that are involved in both the regulation of blood pressure and immune function and as such are excellent targets for further study.
Publication Title
The transcriptome of the medullary area postrema: the thirsty rat, the hungry rat and the hypertensive rat.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- NextSeq 500
Description
Granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs) produce monocytes during homeostasis and in response to increased demand during infection. Both progenitor populations are thought to derive from common myeloid progenitors (CMPs), and a hierarchical relationship (CMP-GMP-MDP-monocyte) is presumed to underlie monocyte differentiation. Here, however, we demonstrate that mouse MDPs arose from CMPs independently of GMPs, and that GMPs and MDPs produced monocytes via similar, but distinct, monocyte-committed progenitors. GMPs and MDPs yielded classical (Ly6Chi) monocytes with gene expression signatures that were defined by their origins and impacted their function. GMPs produced a subset of “neutrophil-like” monocytes, whereas MDPs gave rise to a subset of monocytes that yielded monocyte-derived dendritic cells. GMPs and MDPs were also independently mobilized to produce specific combinations of myeloid cell types following the injection of microbial components. Thus, the balance of GMP and MDP differentiation shapes the myeloid cell repertoire during homeostasis and following infection. Overall design: RNA-seq of myeloid progenitors and Ly6Chi monocytes from mouse bone marrow. 4 progenitor fractions (GMPs, MDPs, GPs and a mixed fraction of MPs + cMoPs) were isolated from the pooled bone marrow of 20 mice. GMPs and MDPs were also cultured in vitro and the monocyte-committed progenitors and Ly6Chi monocytes they produced were also harvested. RNA was extracted from the 4 ex vivo progenitor fractions, and the 4 populations derived in vitro (GMP-derived monocyte progenitors = MP; MDP-derived monocyte progenitors = cMoP; GMP-derived Ly6Chi monocytes = G-mono; MDP-derived Ly6Chi monocytes = M-mono). The whole process was repeated using 20 additional mice to obtain a replicate set of samples.
Publication Title
Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 31 Downloadable Samples
- Illumina HiSeq 2000
Description
Analysis of alveolar macrophage gene expression in C57BL6 wild-type and RAGE null mice exposed to cigarette smoke Overall design: 4 groups of 3-4 mice at two exposure time points (7-day and 4 month), 31 samples total
Publication Title
RAGE is a Critical Mediator of Pulmonary Oxidative Stress, Alveolar Macrophage Activation and Emphysema in Response to Cigarette Smoke.
Sample Metadata Fields
Cell line, Subject, Time
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Treatment of prostate cancer by hormone suppression leads to the appearance of aggressive variants with variable or no dependence on the androgen receptor. Here we show that the developmental transcription factor, ONECUT2, is a master regulator of the AR network that is highly active in castration-resistant prostate cancer (CRPC).
Publication Title
ONECUT2 is a targetable master regulator of lethal prostate cancer that suppresses the androgen axis.
Sample Metadata Fields
Cell line, Treatment
View Samples