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Homo sapiens
29 Downloadable Samples
IlluminaGenomeAnalyzerII
Description
The histological grade of carcinomas describes the ability of tumor cells to organize differentiated epithelial structures and has prognostic impact. Molecular control of differentiation in normal and cancer cells relies on lineage-determining transcription factors (TFs) that activate the repertoire of cis-regulatory elements controlling cell type-specific transcriptional outputs. TF recruitment to cognate genomic DNA binding sites results in the deposition of histone marks characteristic of enhancers and other cis-regulatory elements. Here we integrated transcriptomics and genome-wide analysis of chromatin marks in human pancreatic ductal adenocarcinoma (PDAC) cells of different grade to identify first, and then experimentally validate the sequence-specific TFs controlling grade-specific gene expression. We identified a core set of TFs with a pervasive binding to the enhancer repertoire characteristic of differentiated PDACs and controlling different modules of the epithelial gene expression program. Defining the regulatory networks that control the maintenance of epithelial differentiation of PDAC cells will help determine the molecular basis of PDAC heterogeneity and progression. Overall design: Poly(A) fraction of the total RNA from human pancreatic ductal adenocarcinoma cell lines was extracted and subjected to by multiparallel sequencing. Experiments were carried out in unmodified cells in duplicate, genome edited clonal CFPAC1 cells (2 KLF5-deleted CRISPR-Cas9 clones, 3 ELF3-deleted CRISPR-Cas9 clones and 2 wt clones) and CFPAC1 cells ectopically expressing ZEB1 or empty vector control (in duplicate).
Publication Title
Dissection of transcriptional and cis-regulatory control of differentiation in human pancreatic cancer.
Sample Metadata Fields
No sample metadata fields
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GSE35679- Homo sapiens
- 13 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Global gene expression of 13 frozen samples, 6 from typical and 7 from atypical surgically resected primary lung carcinoids
Publication Title
Gene expression profiling reveals GC and CEACAM1 as new tools in the diagnosis of lung carcinoids.
Sample Metadata Fields
Sex
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The objective of the study was identify hepatic genes with expression by deprivation of gut flora. Two models were used: model 1 (study 1443KR) examined germ-free Sprague Dawley and model 2 (1512KR) examined antibiotic treated Han Wistar rats.
Publication Title
Systemic gut microbial modulation of bile acid metabolism in host tissue compartments.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 50 Downloadable Samples
- Illumina HiSeq 4000
Description
Gastrocnemius muscle biopsies were obtained from 15 health older adults without peripheral artery disease (PAD), 20 PAD patients with intermittent claudication, and 16 patients with critical limb ischemia undergoing limb amputation. Gene expression analysis was performed using RNA sequencing analysis. Overall design: Examination of gene expression differences across the clinical spectrum of PAD (healthy vs. claudicant vs. critical limb ischemia)
Publication Title
Extensive skeletal muscle cell mitochondriopathy distinguishes critical limb ischemia patients from claudicants.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 36 Downloadable Samples
- IlluminaHiSeq2000
Description
Cancer tissue-like structures were developed by using established human tumor cell lines in perfusion-based bioreactor systems. In colorectal cancer (CRC) cell lines, perfusion allowed more homogeneous scaffold seeding than tri-dimensional (3D) static cultures and significantly (13.7 fold, p<0.0001) higher proliferation. Resulting tissues exhibited morphology and phenotypes similar to xenografts generated in immunodeficient mice. Whole transcriptome analysis of 2D, 3D static and 3D perfusion cultures revealed the highest correlation between xenografts and 3D perfusion cultures (r=0.985). Clinically relevant concentrations of 5-FU, used in neo- and adjuvant CRC treatment, had no effect on numbers of HT-29 CRC cells cultured in 3D perfusion or xenografts, as compared with a 55.8% reduction in 2D cultures. Treatment induced apoptosis in 2D cultures, but only “nucleolar stress” in perfused cells and xenografts, consistent with partial responsiveness. In 3D perfusion cultures BCL-2, TRAF1, and FLIP gene expression was marginally affected, as compared with significant down-regulation in 2D cell cultures. Accordingly, ABT-199 BCL-2 inhibitor, induced cytostatic effects in 3D perfusion but not in 2D cell cultures (p=0.003). Tumor cells from partially responsive (Dworak 2) patients undergoing neo-adjuvant treatment, typically (10/11) expressed BCL-2, as compared with 0/3 highly (Dworak 3-4) responsive and 4/15 fully resistant CRC (Dworak 0/1, p=0.03), closely matching 3D perfusion cultures data. These results indicate that 3D perfusion cultures efficiently mimic phenotypic and functional features observed in xenografts and clinical specimens. These models may be of critical translational relevance to address fundamental human tumor cell biology issues and to develop predictive pre-clinical tests of novel compounds. Overall design: Expression profiles of colorectal cancer cell lines cultured in 2D, 3D static, 3D perfusion or growing as xenografts were generated by deep sequencing, in triplicates, using Illumina HiSeq2000.
Publication Title
Bioreactor-engineered cancer tissue-like structures mimic phenotypes, gene expression profiles and drug resistance patterns observed "in vivo".
Sample Metadata Fields
No sample metadata fields
View Samples GSE9482- Saccharomyces cerevisiae
- 40 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
The goal of this set of experiments was to identify transcripts that are differentially expressed upon reactivation of NMD in an nmd2::HIS3 strain by galactose-induced expression of the NMD2 gene.
Publication Title
Association of yeast Upf1p with direct substrates of the NMD pathway.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The activation of endothelium by tumor cells is one of the main steps by tumor metastasis. The role of the blood components (platelets and leukocytes) in this process remain unclear.
Publication Title
Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- NextSeq 500
Description
In response to UVB irradiation, human keratinocytes transiently block cell cycle progression to allow ample time for DNA repair and cell fate determination. These cellular processes are important for evading the initiation of carcinogenesis in skin. We previously showed that repression of mRNA translation initiation through phosphorylation of eIF2a (eIF2a-P) protects keratinocytes from UVB-induced apoptosis. In this study, we elucidate the mechanism of eIF2a-P cytoprotection in response to UVB. Loss of eIF2a-P induced by UVB diminished G1 arrest, DNA repair rate, and cellular senescence coincident with enhanced cell death in human keratinocytes. Genome-wide translation analyses revealed that the mechanism for these critical changes directed by eIF2a-P involved induced expression of CDKN1A encoding p21 protein. p21 is a major regulator of the cell cycle, and we show that human CDKN1A mRNA splice variant 4 is preferentially translated by eIF2a-P during stress in a mechanism mediated in part by upstream ORFs situated in the 5'-leader of CDKN1A mRNA. We conclude that eIF2a-P is cytoprotective in response to UVB by a mechanism featuring translation of a specific splice variant of CDKN1A that facilitates G1 arrest and subsequent DNA repair. Overall design: Untreated and irradiated N-TERT keratinocytes are split into 3 groups: monosome fraction, polysome fraction, and whole cell lysate. N=3.
Publication Title
Translational control of a human <i>CDKN1A</i> mRNA splice variant regulates the fate of UVB-irradiated human keratinocytes.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Saccharomyces cerevisiae
- 8 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
The goal of this experiment was to identify transcripts associated with the S. cerevisiae Upf1 protein.
Publication Title
Association of yeast Upf1p with direct substrates of the NMD pathway.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 74 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Understanding the structure and interplay of cellular signalling pathways is one of the great challenges in molecular biology. Boolean Networks can infer signalling networks from observations of protein activation. In situations where it is difficult to assess protein activation directly, Nested Effect Models are an alternative. They derive the network structure indirectly from downstream effects of pathway perturbations. To date, Nested Effect Models cannot resolve signalling details like the formation of signalling complexes or the activation of proteins by multiple alternative input signals. Here we introduce Boolean Nested Effect Models (B-NEM). B-NEMs combine the use of downstream effects with the higher resolution of signalling pathway structures in Boolean Networks. We show that B-NEMs accurately reconstruct signal flows in simulated data. Using B-NEM we then resolve BCR signalling via PI3K and TAK1 kinases in BL2 lymphoma cell lines.
Publication Title
Analyzing synergistic and non-synergistic interactions in signalling pathways using Boolean Nested Effect Models.
Sample Metadata Fields
Specimen part, Cell line, Treatment
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