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Saccharomyces cerevisiae
14 Downloadable Samples
Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The main objectives of this study were to expand our understanding of NSF1 gene function in industrial S. cerevisiae M2 strain during fermentation by finding the largest maximal clique of co-expressed genes (i.e. Interdependent Correlation Cluster), and to establish the impact of Nsf1p on genome-wide gene expression during the fermentation process with possible implications related to wine quality and S. cerevisiae adapation to stressful fermentation conditions
Publication Title
Functional analyses of NSF1 in wine yeast using interconnected correlation clustering and molecular analyses.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The satellite cell is considered the major tissue-resident stem cell underlying muscle regeneration, however, multiple non-satellite cell myogenic progenitors have been identified. PW1/Peg3 is expressed in satellite cells as well as a subset of interstitial cells with myogenic potential termed PICs (PW1+ Interstitial Cells). PICs differ from satellite cells by their anatomical location (satellite cells are sublaminal and PICs are interstitial), they do not express any myogenic marker and arise from a Pax3-independent lineage. Upon isolation from juvenile muscle (1 to 3 weeks old), PICs are capable to form both skeletal and smooth muscle suggesting they constitute a more plastic population compared to satellite cells. We used microarrays to gain insight into the relantionship between PICs and satellite cells.
Publication Title
Defining skeletal muscle resident progenitors and their cell fate potentials.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
Illumina HiSeq 2000
Description
Pre-B and pre-T lymphocytes must orchestrate a transition from a highly proliferative state to a quiescent one during development. Cyclin D3 is essential for these cells’ proliferation, but little is known about its post-translational regulation at this stage. Here, we show that the dual specificity tyrosine-regulated kinase 1A (DYRK1A) restrains Cyclin D3 protein levels by phosphorylating T283 to induce its degradation. Loss of DYRK1A activity, via genetic inactivation or pharmacologic inhibition, caused accumulation of Cyclin D3 protein, incomplete repression of E2F-mediated gene transcription, and failure to properly couple cell cycle exit with differentiation. Expression of a non-phosphorylatable Cyclin D3 T283A mutant recapitulated these defects, while inhibition of Cyclin D:CDK4/6 mitigated the effects of DYRK1A inhibition. These data uncover a previously unknown role for DYRK1A in lymphopoiesis, and demonstrate how Cyclin D3 protein stability is negatively regulated during exit from the proliferative phases of B and T cell development. Overall design: 5 cell populations were analyzed (small pre-B cells, large pre-B cells, quiescent CD4+CD8+ thymocytes, cycling CD4+CD+ thymocytes, and mature granulocytes) from 2 Control mice (pooled) and 2 DYRK1A-deficient mice (pooled) for a total of 10 samples.
Publication Title
DYRK1A controls the transition from proliferation to quiescence during lymphoid development by destabilizing Cyclin D3.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Low levels of the cell cycle regulator p27Kip1 are associated with a worse outcome in many tumor types. We report here a new regulatory role of p27Kip1 as a transcriptional regulator. In association with transcriptional factors such as ETS and E2F4 and co-repressors like p130, HDACs and mSin3A, p27 binds to promoters of multiple genes leading to their repression. The p27-target genes participate in RNA processing, translation, respiration and cell cycle. Remarkably, p27-target genes are over-expressed in different human tumors in tight association with a poor clinical prognosis. We also observed a clear correlation between low levels of p27 and over-expression of p27-target genes in tumors. Overall, our findings indicate new tumor suppressor roles of p271 as a transcriptional regulator of genes relevant for oncogenesis.
Publication Title
p27Kip1 represses transcription by direct interaction with p130/E2F4 at the promoters of target genes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Conjugated linoleic acid (CLA), a class of fatty acids found in beef and dairy products, has been shown to inhibit tumorigenesis in a variety of cancer model systems. Based on previously well-documented anti-tumor activity of CLA in rodent models of breast cancer, a pilot study was initiated to examine the effect of dietary CLA in a well-established transgenic model of breast cancer. Western blots were performed for the detection of AKT, c-Src, ERK1/2, and Cdc24. CLA significantly increased tumor burden (p<0.1) independent of an increase in oncogenic signaling. Mammary gland whole mounts indicated a loss of mammary adipose and extensive epithelial expansion in CLA-treated animals. Microarray analysis indicated a significant reduction in cytoskeletal related genes with at least a two-fold decrease in five out of six CLA-fed animals compared to untreated controls. Reduction of Cdc42, a key regulator of cell adhesion and cytoskeletal arrangements, was confirmed at the protein level by western blot (p<0.01). These findings suggest that dietary CLA may advance the malignant phenotype by promoting a loss of cell polarity and adhesion in the mammary gland epithelium. This action may have serious clinical implications for a subset high-risk population and warrants further investigation.
Publication Title
Pilot study on the effects of dietary conjugated linoleic acid on tumorigenesis and gene expression in PyMT transgenic mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Epithelial ovarian cancer is a very heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Rational therapeutic approaches need to account for interpatient and intratumoral heterogeneity in treatment design. Detailed characterization of in vitro models representing the different histological and molecular subtypes is therefore imperative. Strikingly, from ~100 available ovarian cancer cell lines the origin and which subtype they represent is largely unknown. We have extensively and uniformly characterized 39 ovarian cancer cell lines (with mRNA/microRNA expression, exon sequencing, dose response curves for clinically relevant therapeutics) and obtained all available information on the clinical features and tissue of origin of the original ovarian cancer to refine the putative histological subtypes. From 39 ovarian cell lines, 14 were assigned as high-grade serous, four serous-type, one low-grade serous and 20 non-serous type. Three morphological subtypes (21 Epithelial, 7 Round, 12 Spindle) were identified that showed distinct biological and molecular characteristics, including overexpression of cell movement and migration-associated genes for the Spindle subtype. Clinical validation showed a clear association of the spindle-like tumors with metastasis, advanced stage, suboptimal debulking and poor prognosis. In addition, the morphological subtypes associated with the molecular C1-6 subtypes identified by Tothill et al. [1], Spindle clustered with C1-stromal subtype, Round with C5-mesenchymal and Epithelial with C4 subtype. We provide a uniformly generated data resource for 39 ovarian cancer cell lines, the ovarian cancer cell line panel (OCCP). This should be the basis for selecting models to develop subtype specific treatment approaches, which is very much needed to prolong the survival of ovarian cancer patients.
Publication Title
Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes.
Sample Metadata Fields
Cell line
View Samples
GSE1847- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Hepatic gene expression analysis in mice fed control diet or diets supplemented with 1% Fraction 1 (haxane) or Fraction 2 (methanol) of Boswellia Serrata
Publication Title
Effects of Boswellia serrata in mouse models of chemically induced colitis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Decreased mitochondrial mass and function in muscle of diabetic patients is associated with low PGC-1alpha, a transcriptional coactivator of the mitochondrial gene program. To investigate whether reduced PGC-1alpha and oxidative capacity in muscle directly contributes to age-related glucose intolerance, we compared the genetic signatures and metabolic profiles of aging mice lacking muscle PGC-1alpha. Microarray analysis revealed that a significant proportion of PGC-1alpha-dependent changes in gene expression overlapped with age-associated effects, and aging muscle and muscle lacking PGC-1alpha shared gene signatures of impaired electron transport chain activity and TGFbeta signalling.
Publication Title
Loss of Pgc-1α expression in aging mouse muscle potentiates glucose intolerance and systemic inflammation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina Genome Analyzer
Description
Coordinated BCR-ABL1 kinase-dependent and -independent mechanisms convert p27 from a nuclear tumor suppressor to a cytoplasmic oncogene. Persistence of oncogenic p27 functions despite effective inhibition of BCR-ABL1 may contribute to resistance to tyrosine kinase inhibitors. Overall design: BCR-ABL1 induced p27 versus knockout, controlling with Empty vector p27 versus knock out
Publication Title
BCR-ABL1 promotes leukemia by converting p27 into a cytoplasmic oncoprotein.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- NextSeq 500
Description
BRAF oncogene is mutated in ~50% of human cutaneous melanomas. The BRAF V600E mutation leads to constitutive activation of the mitogen-activated protein kinase (MAPK) pathway fuelling cancer growth. The inhibitors of BRAF V600E (BRAFi), lead to massive and high response rate. However, BRAFi-resistant cells that operate as a cellular reservoir for relapses severely limits the duration of the clinical response. The recent depiction of these resistant cells did not identify druggable targets to ensure long-term survival under BRAFi. Here, we identify the aryl hydrocarbon receptor (AhR) as a target to eradicate resistant cells. We show that BRAFi bind to AhR on a new site, named beta-pocket, and reprogram gene expression independently of its partner ARNT. beta-pocket activation induces a pigmentation signature, which is associated to BRAFi-induced cell death of sensitive BRAF V600E melanoma cells and tumour shrinkage. Intriguingly, in resistant cells, BRAFi does not induced a pigmentation signature since these cells display another AhR program; AhR-ARNT dependant. By this way, AhR directs several key BRAFi-resistant genes. At single cell level, this constitutive activation of AhR-ARNT is identified in rare cells before BRAFi-treatment of melanoma tumours and an enrichment of these alpha-cells is observed under BRAFi. Our data strongly suggest that an endogenous AhR ligand activates AhR-ARNT via the canonical AhR pocket (alpha-pocket), thus favouring BRAFi-resistant gene expression. Importantly, we identify the clinically compatible AhR antagonist, the resveratrol (RSV), able to abrogate the deleterious constitutive activation of AhR and to reduce the cellular reservoir for the relapse. Taken together, this work reveals that constitutive AhR signalling drives BRAFi resistance and constitutes a therapeutic target to achieve long-term patient survival under BRAFi. More broadly, the constitutive activation of AhR by endogenous ligands is in line with the ability of UV radiations to generate potent AhR ligands and to favour melanoma onset. Overall design: Total RNA isolated from 12 human melanoma cell lines (501Mel) after different treatments was subjected to multiplexed RNA-sequencing using Illumina NextSeq500 sequencing tehnology.
Publication Title
Sustained activation of the Aryl hydrocarbon Receptor transcription factor promotes resistance to BRAF-inhibitors in melanoma.
Sample Metadata Fields
Specimen part, Cell line, Subject
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