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GSE19605
Mus musculus
24 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
A large amount of epidemiologic data supports a role for chronic inflammation in epithelial carcinogenesis. In the lung, several studies have found that smokers with chronic obstructive pulmonary disease (COPD), an inflammatory disease of the airways and alveoli, have an increased risk of lung cancer (1.3 to 4.9 fold) compared to smokers without COPD. We have also shown that COPD-like airway inflammation induced by an aerosolized lysate of non-typeable Hemophilus influenzae (NTHi) promotes lung cancer in a Clara cell-targeted K-ras mutant mouse model (CC-LR) of lung cancer. In contrast, existing epidemiologic data suggest that allergic inflammation of the airways may be protective against lung cancer. We tested this association in a mouse model of allergic airway inflammation. CC-LR mice were sensitized to ovalbumin by intraperitoneal injection weekly for two weeks, then challenged for 30 min to an aerosol of ovalbumin in 0.9% saline weekly for eight weeks. This resulted in eosinophilic lung inflammation associated with increased levels of T helper 2 (Th2) cytokines and mucous metaplasia of airway epithelium, similar to what is seen in asthma patients. However, consistent with epidemiologic data, this type of inflammation did not result in any significant differences in lung surface tumor number (22 3 in OVA exposed vs 26 6 in control mice). We conclude that asthma-like (Th2) inflammation does not promote lung carcinogenesis in a Ras-initiated background, and demonstrate a clear specificity for the nature of inflammation in lung cancer promotion. These findings will assist in determination of the essential cells and signaling events in lung cancer promotion by inflammation.
Publication Title
Interleukin 6, but not T helper 2 cytokines, promotes lung carcinogenesis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
Purpose: berrantly high expression of TRIM24 occurs in human cancers, including hepatocellular carcinoma. In contrast, TRIM24 in the mouse is reportedly a liver-specific tumor suppressor. To address this dichotomy and uncover direct regulatory functions of TRIM24 in vivo, we developed a new mouse model that lacks expression of all Trim24 isoforms, as the previous model expresses normal levels of Trim24 lacking only exon 4. Methods: To produce germline-deleted Trim24dlE1 mice, deletion of the promoter and exon 1 of Trim24 was induced in Trim24LoxP mice by crossing with a zona pellucida 3-Cre line for global deletion. Liver-specific deletion (Trim24hep) was achieved by crossing with an Albumin-Cre line. Phenotypic analyses were complemented by protein, gene-specific and global RNA expression analyses and quantitative chromatin immunoprecipitation. Results:Global loss of Trim24 disrupted hepatic homeostasis in 100% of mice with highly significant, decreased expression of oxidation/reduction, steroid, fatty acid and lipid metabolism genes, as well as increased expression of genes in unfolded protein, endoplasmic reticulum stress and cell cycle pathways. Trim24dlE1/dlE1 mice have markedly depleted visceral fat and, like Trim24hep/hep mice, spontaneously develop hepatic lipid-filled lesions, steatosis, hepatic injury, fibrosis and hepatocellular carcinoma. Conclusions: TRIM24, an epigenetic co-regulator of transcription, directly and indirectly represses hepatic lipid accumulation, inflammation, fibrosis and damage in the murine liver. Complete loss of Trim24 offers a model of human nonalcoholic fatty liver disease, steatosis, fibrosis and development of hepatocellular carcinoma in the absence of high-fat diet or obesity. Overall design: mRNA profiles of 8 weeks wild type (WT) and Trim24-/- mice were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000
Publication Title
TRIM24 suppresses development of spontaneous hepatic lipid accumulation and hepatocellular carcinoma in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
Purpose: identify sites in endogenous mRNAs that are cut by KSHV SOX; Method: parallel analysis of RNA ends (PARE, following Zhai et al., 2014); Results: SOX cuts at discrete locations in mRNAs Overall design: human Xrn1 was knocked down in HEK293T cells by shRNAs or siRNAs to stabilize degradation fragments with free 5'' ends; GFP-SOX or GFP were transfected for ~24 hrs; total RNA samples were collected and subjected to PARE protocol (Zhai et al., 2014)
Publication Title
Transcriptome-Wide Cleavage Site Mapping on Cellular mRNAs Reveals Features Underlying Sequence-Specific Cleavage by the Viral Ribonuclease SOX.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 21 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
In this study Panc-1 cells and BxPC-3 cells were cultured. The cells were harvested (untreated control 'cont') for RNA extraction, or treated for 3 hours with various exosomes preparations. The exosomes were collected from BJ human foreskin fibroblast culture supernatant without further processing (control exosomes or 'CE'), or engineered to contain scrambled siRNA ('scr') or KRASG12D siRNA ('iExo). Two or three distinct wells of cells were evaluated per treatment condition and assigned a well number (well -1, -2 or 3).
Publication Title
Generation and testing of clinical-grade exosomes for pancreatic cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transient expression of two factors, or from Oct4 alone, resulted in efficient generation of human iPSCs. The reprogramming strategy described revealed a potential transcriptional signature for human iPSCs yet retaining the gene expression of donor cells in human reprogrammed cells free of viral and transgene interference.
Publication Title
Transcriptional signature and memory retention of human-induced pluripotent stem cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: NGS has revolutionized systems-based analysis of cell signaling pathways. The goal of this study is to determine the effects of PPARD in colon cancer cell transcriptomes in relation to the metastatic potential. Methods: NGS-derived colon cancer cell mRNA transcriptome profiles of HCT116 WT (HCT116) and HCT116 with genetic PPARD-knockout (KO1) cells were generated by deep sequencing, in quadruplicate, using Illumina HiSeq2000 .The transcriptomes of HCT116 and KO1 cells will be compared to determine the differentially expressed genes between HCT116 and KO1 cells. Differentially expressed genes will be examined in relation to the metastatic potential and validated by qRT-PCR. Results: Using an optimized data analysis workflow Tophat2, we mapped about 25 million sequence reads per sample to the human genome. Out of 22229 genes, we identified 12118 transcripts with >50 reads in at least one sample of HCT116 and KO1 cells with edgeR package and identified 6668 differentailly expressed genes with FDR 0.001 and P value cutoff 0.0022 using GLM tests fitted with BUM model. We further fltered the genes with both p-value and fold change and identified 416 genes with FDR 0.001 and fold change larger than 2. Among the differentially expressed genes, 311 were downregulated and 105 were upregulated in the KO1 cells compared with the WT cells. Twenty-three of the differentially expressed genes had significant association (i.e., a tendency towards co-occurrence) with PPARD expression (P < 0.05; log odds ratio > 1.5) in the TCGA colorectal adenocarcinoma database. Of these 23 genes, 7 were linked to metastasis by PubMed literature searches: GJA1, VIM, SPARC, NRG1, CXCL8 (IL-8), STC1, and SNCG, which were validated by q-RT-PCR. Conclusions: Our study represents the detailed analysis of PPARD transcriptomes in colon cancer cells, generated by mRNA-seq technology. Our results show that NGS offers a comprehensive and accurate quantitative and qualitative evaluations of mRNA contents in cells. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions. Overall design: The transcriptome profiles of HCT116 WT and KO1 colon cancer cells were generated by deep sequencing, in quadruplicate, using Illumina HiSeq2000.
Publication Title
Metastasis regulation by PPARD expression in cancer cells.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 26 Downloadable Samples
- Illumina HiSeq 2500
Description
To elucidated through an unbiased manner which genes and pathways are differentially regulated during mouse colonic inflammation followed by a tissue regeneration phase. In particular, we took advantage of the widely used dextran sodium sulfate (DSS)-induced model of colitis. This model is one of the few characterized by a phase of damage followed by a phase of regeneration. Therefore, this model gave the possibility to identify also sets of genes essential in the regeneration phase, a key step towards the resolution of the inflammation. In short, mice were exposed to DSS in the drinking water for 7 days, then allowed to recover for the following 7 days. During this period, we collected colonic tissue samples every second day to then be analyzed by RNA sequencing (RNA-seq). Next, we performed a RNA-seq analysis from colonic samples throughout the experiment and computed differentially expressed genes (DEGs) taking the complete kinetics of expression into consideration for p-value estimation using EdgeR. Overall design: C57BL/6J female mice were treated with 2.5% DSS in order to induce colinic inflammation. 2-3 animals were sacrificed at different time points when the colonic tissue was collected.
Publication Title
Conserved transcriptomic profile between mouse and human colitis allows unsupervised patient stratification.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
L1 retrotransposons are active elements in the genome, capable of mobilization in neuronal progenitor cells. Previously, we showed that chromatin remodeling during neuronal differentiation allows for a transient stimulation of L1 transcription. The activity of L1 retrotransposons during brain development can impact gene expression and neuronal function. Here we show that L1 neuronal retrotransposition in rodents is increased in the absence of MeCP2, a protein involved in global methylation and human neurodevelopmental diseases. Using neuronal progenitor cells derived from human induced pluripotent stem cells and human tissues, we revealed that Rett syndrome patients, with MeCP2 mutations, have increased susceptibility for L1 retrotransposition. Our data demonstrate that disease-related genetic mutations can influence the frequency of neuronal L1 retrotransposition, thereby increasing brain-specific genetic mosaicism.
Publication Title
A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Self-renewal of embryonic stem cells (ESCs) cultured in serum-LIF is incomplete with some cells initiating differentiation. While this is reflected in heterogeneous expression of naive pluripotency transcription factors (TFs), the link between TF heterogeneity and differentiation is not fully understood. Here we purify ESCs with distinct TF expression levels from serum-LIF cultures to uncover early events during commitment from nave pluripotency. ESCs carrying fluorescent Nanog and Esrrb reporters show Esrrb downregulation only in NANOGlow cells. Independent Esrrb reporter lines demonstrate that ESRRBnegative ESCs cannot effectively self-renew. Upon ESRRB loss, pre-implantation pluripotency gene expression collapses. ChIP-Seq identifies different regulatory element classes that bind both OCT4 and NANOG in ESRRBhigh cells. Class I elements lose NANOG and OCT4 binding in ESRRBnegative ESCs and associate with genes expressed preferentially in nave ESCs. In contrast, class II elements retain OCT4 but not NANOG binding in ESRRBnegative cells and associate with more broadly expressed genes. Therefore, mechanistic differences in TF function act cumulatively to restrict potency during exit from nave pluripotency.
Publication Title
Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation.
Sample Metadata Fields
Specimen part
View Samples