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GSE26391
Homo sapiens
8 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The epithelial to mesenchymal transition (EMT) of malignant hepatocytes is a crucial event in hepatocellular carcinoma (HCC) progression and recurrence. We aimed to establish a human model of EMT to examine drug efficacy and specificity in HCC progression. Human HCC cell populations were characterized by immunofluorescence analysis, migration and invasion assays, array comparative genomic hybridization, whole-genome expression profiling and promoter methylation. Therapeutic agents clinically used against HCC were examined for efficacy by determination of IC50 values. Liver cancer cell lines showed either an epithelial or mesenchymal phenotype of which latter showed strong migratory and invasive abilities in vitro. The common cellular origin of both cell types indicated that mesenchymal HCC cells have been derived from epithelial hepatocytes through EMT in the HCC patient. Drug exposure of mesenchymal HCC cells showed higher resistance to the targeted therapeutic agents sorafenib and erlotinib as compared to epithelial HCC cells, which were slightly more resistant to cytostatic drugs. Most remarkably, combined treatment with doxorubicin and sorafenib caused increased susceptibility of both HCC cell types resulting in enhanced drug efficacy. Taken together, this novel model of human HCC allows to monitor the differential effect of liver cancer progression on drug efficacy in pre-clinical studies.
Publication Title
A human model of epithelial to mesenchymal transition to monitor drug efficacy in hepatocellular carcinoma progression.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Background and aims: Signal transducer and activator of transcription 3 (Stat3) is the main mediator of interleukin-6 type cytokine signaling required for hepatocyte proliferation and hepatoprotection but its role in sclerosing cholangitis (SC) and other cholestatic liver diseases remains unresolved. Methods: We investigated the role of Stat3 in inflammation-induced cholestatic liver injury and used mice lacking the multidrug resistance gene 2 (mdr2-/-) as a model for SC. Results: We demonstrate that conditional inactivation of stat3 in hepatocytes and cholangiocytes (stat3hc) of mdr2-/- mice strongly aggravated bile acid-induced liver injury and fibrosis. Similarly, stat3hc mice are more sensitive to cholic acid feeding than control mice. Global gene expression analysis demonstrated that hepatoprotective signals via epidermal growth factor and insulin-like growth factor 1 are affected upon loss of Stat3. Conclusions: Our data suggest that Stat3 protects cholangiocytes and hepatocytes from bile acid-induced damage thereby preventing liver fibrosis in cholestatic diseases.
Publication Title
Signal transducer and activator of transcription 3 protects from liver injury and fibrosis in a mouse model of sclerosing cholangitis.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 28 Downloadable Samples
Illumina HiSeq 2500
Description
To determine the role of the cytokine activin A in the regulation of human T follicular helper (Tfh) cell gene program, we performed a transcriptomic analysis (RNA-seq) of human naïve CD4 T cells differentiated in vitro with activin A. The analysis of the gene expression profile driven by activin A, alone or in combination with IL-12 (a know regulator of human Tfh differentiation/function), revealed that activin A can regulate the expression of multiple molecules involved in the differentiation and/or function of human Tfh cells. Overall design: Human naïve CD4 T cells were isolated from fresh PBMCs of healthy control subjects by magnetic bead isolation. Purity was measured by FACS as percentage of CD4+CD45RA+ cells and was 95% or higher. Upon isolation, naïve CD4 T cells were stimulated with anti-CD3/CD28 coated beads in the presence of the following cytokine combinations: no exogenous cytokines (beads only), activin A, IL-12, activin A+IL-12, TGFb, TGFb +IL12. Following 5 days of in vitro culture, live CD4 T cells were FACS sorted and gene expression was analyzed by RNA-seq. Data are from independent donors.
Publication Title
Activin A programs the differentiation of human TFH cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
17b-Estradiol added to MEL cells expressing Gata1-ER or PU.1-ER transgenes to stimulate either erythropoietic Gata-1 dependent or myeloid PU.1 dependent gene espression in different time points
Publication Title
PU.1 activation relieves GATA-1-mediated repression of Cebpa and Cbfb during leukemia differentiation.
Sample Metadata Fields
Disease, Disease stage
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Comparative analysis of gene expression in cultured primary keratinocytes isolated from newborn control (K14-cre; GPx4fl/+) and knockout (K14-cre; GPx4fl/fl) mice.
Publication Title
Targeted disruption of glutathione peroxidase 4 in mouse skin epithelial cells impairs postnatal hair follicle morphogenesis that is partially rescued through inhibition of COX-2.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
In this study, we present a comprehensive evaluation of four RNA-Seq library preparation methods. We used three standard input protocols, the Illumina TruSeq Stranded Total RNA and TruSeq Stranded mRNA kits, and a modified NuGEN Ovation v2 kit; and an ultra-low-input RNA protocol, the TaKaRa SMARTer Ultra Low RNA Kit v3. Our evaluation of these kits included quality control measures such as overall reproducibility, 5' and 3' end-bias, and the identification of DEGs, lncRNAs, and alternatively spliced transcripts. Overall, we found that the two Illumina kits were most similar in terms of recovering DEGs, and the Illumina, modified NuGEN, and TaKaRa kits allowed identification of a similar set of DEGs. However, we also discovered that the Illumina, NuGEN and TaKaRa kits each enriched for different sets of genes. Overall design: Two mESC cell lines (biological replicates) from Zbtb24 knockout (1lox/1lox) clones are compared with two wild-type (2lox/+) clones (biological replicates) using the TaKaRa SMARTer Ultra Low RNA protocol directly on cells with no RNA preparation step. Total RNA from 100 mESCs cells and 1000 mESCs cells or approximately 1 and 10 ng RNA were used respectively.
Publication Title
Systematic evaluation of RNA-Seq preparation protocol performance.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
In this study, we present a comprehensive evaluation of four RNA-Seq library preparation methods. We used three standard input protocols, the Illumina TruSeq Stranded Total RNA and TruSeq Stranded mRNA kits, and a modified NuGEN Ovation v2 kit; and an ultra-low-input RNA protocol, the TaKaRa SMARTer Ultra Low RNA Kit v3. Our evaluation of these kits included quality control measures such as overall reproducibility, 5' and 3' end-bias, and the identification of DEGs, lncRNAs, and alternatively spliced transcripts. Overall, we found that the two Illumina kits were most similar in terms of recovering DEGs, and the Illumina, modified NuGEN, and TaKaRa kits allowed identification of a similar set of DEGs. However, we also discovered that the Illumina, NuGEN and TaKaRa kits each enriched for different sets of genes. Overall design: Three mESC cell lines (biological replicates) from Zbtb24 knockout (1lox/1lox) clones are compared with three wild-type (2lox/+) clones (biological replicates) using the TruSeq mRNA protocol.
Publication Title
Systematic evaluation of RNA-Seq preparation protocol performance.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina HiSeq 2500
Description
Mononuclear phagocytes are a diverse cell family that occupy all tissues and assume numerous functions to support tissue and systemic homeostasis. Our ability to investigate the roles of individual subsets is limited by an absence of approaches to ablate gene function within specific sub-populations. Using Nr4a1-dependent Ly6Clow monocytes as a representative cell type we show that enhancer deletion addresses these limitations. Combining ChIP-Seq and molecular approaches we identify a single, conserved, sub-domain within the Nr4a1 enhancer that is essential for Ly6Clow monocyte development. Mice lacking this enhancer lack Ly6Clow monocytes but retain Nr4a1 gene expression in macrophages during steady state and in response to LPS. Nr4a1 is a key negative regulator of inflammatory gene expression and decoupling these processes allows Ly6Clow monocytes to be studied without confounding influences. Enhancer targeting possesses greater specificity than cre recombinase-mediated gene deletion, providing a route to generate loss-of-function models in closely related cell types. Overall design: Paired End mRNA sequencing of FACS purified primary murine MDP, cMoP, Ly6Chi and Ly6Clow monocytes from the bone marrow and Ly6Chi and Ly6Clow monocytes from the peripheral blood
Publication Title
Deleting an Nr4a1 Super-Enhancer Subdomain Ablates Ly6C<sup>low</sup> Monocytes while Preserving Macrophage Gene Function.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Innate immune responses must be regulated in the intestine to prevent excessive inflammation. Here, using gene reporter mice, we show that a subset of mouse colonic macrophages constitutively produced the anti-inflammatory cytokine IL-10. In mice infected with Citrobacter rodentium, which is considered similar to enteropathogenic Escherichia coli infection in humans, macrophage IL-10 was required to prevent intestinal pathology and to promote survival. The synthesis of the proinflammatory cytokine IL-23 was significantly increased in infected mice with a myeloid cell specific deletion of IL-10 and the addition of IL-10 reduced in vitro IL-23 production by intestinal macrophages. Furthermore, blockade of IL-23 led to reduced morbidity and mortality in the context of macrophage IL-10 deficiency. Transcriptome analysis indicated that the reporter positive and negative colonic macrophage subsets were highly similar, but the reporter positive cells differed for the expression of CD163, an IL-10 target gene, suggesting an autocrine IL-10 signal, and when obtained from infected mice, they had reduced IL-23p19 mRNA. Interestingly, only transfer of the reporter positive cells could rescue IL-10 deficient infected mice. Therefore, these data indicate a pivotal role for a subset of intestinal macrophages that constitutively produces IL-10, perhaps acting in part in autocrine fashion, in controlling excessive innate immune activation, regulation of IL-23 production, and prevention of tissue damage after an acute bacterial infection in the intestine.
Publication Title
IL-10-producing intestinal macrophages prevent excessive antibacterial innate immunity by limiting IL-23 synthesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We aimed at identifying lymphangiogenic subpopulations by comparative analysis of single cell clones derived from a melanoma of a single patient. Selected clones were grafted into SCID mice, where they induced lymphangiogenesis and metastasized into sentinel nodes, whereas non-lymphangiogenic clones from the same patient did not metastasize. RNA isolated from primary SCID mouse tumors were used for transcriptome analysis.
Publication Title
MET expression in melanoma correlates with a lymphangiogenic phenotype.
Sample Metadata Fields
No sample metadata fields
View Samples