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Mus musculus
11 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Death receptor-mediated hepatocyte apoptosis is implicated in a wide range of liver diseases including viral hepatitis, alcoholic hepatitis, ischemia/reperfusion injury, fulminant hepatic failure, cholestatic liver injury and cancer. Deletion of NF-B essential modulator in hepatocytes (Nemohepa) causes the spontaneous development of hepatocellular carcinoma preceded by steatohepatitis in mice and thus serves as an excellent model for the progression from chronic hepatitis to liver cancer. In the present study we aimed to dissect the death-receptor mediated pathways that contribute to liver injury in Nemohepa mice. Therefore, we generated Nemohepa/TRAIL-/- and Nemohepa/TNFR1-/- animals and analyzed the progression of liver injury. Nemohepa/TRAIL-/- displayed a similar phenotype to Nemohepa mice characteristic of high apoptosis, infiltration of immune cells, hepatocyte proliferation and steatohepatitis. These pathophysiological features were significantly ameliorated in Nemohepa/TNFR1-/- livers. Hepatocyte apoptosis was increased in Nemohepa and Nemohepa/TRAIL-/- mice while Nemohepa/TNFR1-/- animals showed reduced cell death concomitant with a strong reduction in pJNK levels. Cell cycle parameters were significantly less activated in Nemohepa/TNFR1-/- livers. Additionally, markers of liver fibrosis and indicators of tumour progression were significantly decreased in these animals. The present data demonstrate that the death receptor TNFR1 but not TRAIL is important in determining progression of liver injury in hepatocyte-specific Nemo knockout mice.
Publication Title
TNFR1 determines progression of chronic liver injury in the IKKγ/Nemo genetic model.
Sample Metadata Fields
Sex, Specimen part
View Samples- Synthetic construct, Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
microRNAs, important regulators of cell proliferation and apoptosis, have been shown to be involved in the pathogenesis of acute myeloid leukemia in adulthood AML. However, comprehensive studies in AML of children and adolescents are missing so far. We investigated the miRNA expression profiles of different AML subtypes from 102 pediatric patients in comparison to CD34+ cells from healthy donors and adult AML patients, in order to identify differentially expressed miRNAs. Pediatric samples with core factor binding acute myeloid leukemia and promyelocytic leukemia could be distinguished from each other and MLL rearranged AML subtypes by 9 and 18 miRNAs, respectively. miR-126, -146a, -181a/b, -100, and miR-125b were identified as highest differentially expressed with marked difference of expression between pediatric and adulthood samples of the same cytogenetic subgroup. We next isolated the miRNA targeting complex from t(8;21) and t(15;17) cell line models and comprehensively identified bound miRNAs and targeted mRNAs by a newly devised immunoprecipitation assay followed by rapid microarray detection. Our findings indicate separate binding preferences for the four human Argonaute proteins. Subsequent bioinformatic analysis revealed a concerted action of different Ago proteins in the regulation of AML-relevant pathways, providing an experimental based database of miRNA-mRNA target interaction in Argonaute proteins.
Publication Title
MicroRNAs distinguish cytogenetic subgroups in pediatric AML and contribute to complex regulatory networks in AML-relevant pathways.
Sample Metadata Fields
Specimen part
View Samples
GSE15757- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
We found the PRC2 component EZH2 to be upregulated by the pathognomonic fusion oncogene EWS-FLI1 in Ewing tumors and mesenchymal stem cells (Richter GH et al., Proc Natl Acad Sci U S A. 2009;106:5324-9). Downregulation of EZH2 by RNA interference in Ewing tumor cell lines suppressed oncogenic transformation in vitro and in vivo. These data suggest that EZH2 might play a central role in Ewing Tumor pathology.
Publication Title
Epigenetic maintenance of stemness and malignancy in peripheral neuroectodermal tumors by EZH2.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The impact of TEL-AML1 (ETV6-RUNX1) expression in precursor B cells and implications for leukaemia using three different genome-wide screening methods.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We identified directly and indirectly regulated target genes utilizing an inducible TEL-AML1 system derived from the murine pro B-cell line BA/F3 and a monoclonal antibody directed against TEL-AML1. By integration of promoter binding identified with ChIP-on-chip, gene expression and protein output through microarray technology and stable labelling of amino acids in cell culture (SILAC), we identified directly and indirectly regulated targets of the TEL-AML1 fusion protein.
Publication Title
The impact of TEL-AML1 (ETV6-RUNX1) expression in precursor B cells and implications for leukaemia using three different genome-wide screening methods.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
The translocation t(7;12)(q36;p13) occurs in infants and very young children with AML and usually has a fatal prognosis. Whereas the transcription factor ETV6, located at chromosome 12p13, has largely been studied in different leukemia types, the influence of the translocation partner HB9 (chr. 7q36), is still unknown. This is particularly surprising as ectopic expression of HB9 is the only recurrent molecular hallmark of translocation t(7;12) AML. We investigated the influence of HB9 as a potential oncogene on cell proliferation and cell cycle in vitro, as well as on hematopoietic stem cell differentiation in vivo using murine and human model systems. We show, that HB9 induces premature senescence in human HT1080 and murine NIH3T3 cells, providing for the first time evidence for an oncogenic potential of HB9. Furthermore, HB9-transduced primary murine hematopoietic stem and progenitor cells underwent a profound differentiation arrest and accumulated at the megakaryocyte/erythrocyte progenitor stage, resulting in a premalignant myeloid cell population in vivo. Concomitantly, HB9 expression upregulates erythropoiesis-related genes in primary human hematopoietic stem and progenitor cells, and enriches gene expression profiles for cell cycle and mitosis-related biological processes. In summary, the novel findings of HB9 dependent premature senescence and perturbed hematopoietic differentiation shed light on the oncogenic properties of HB9 in translocation t(7;12) AML and offer novel targets for therapeutic intervention. Overall design: CD34+ cells were transduced with either GFP or HB9
Publication Title
The homeobox transcription factor HB9 induces senescence and blocks differentiation in hematopoietic stem and progenitor cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 119 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
DS-ALL is a highly heterogeneous disease with predominance of an aberrant exp. of CRLF2 cooperating with mutated JAK2
Publication Title
Down syndrome acute lymphoblastic leukemia, a highly heterogeneous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the International BFM Study Group.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
T4 and T5 neurons are components of the neuronal circuit for motion vision in flies. To identify genes involved in neuronal computation of T4 and T5 neurons, we perfomed transcriptome analysis. Nuclei of T4 and T5 neurons were immunoprecipitated, total RNA was harvested and used for mRNA-seq with Illumina technology. In two biological replicates, we mapped 154 and 119 million reads to D. melanogaster genome. mRNA-seq provided information about expression levels of 17,468 annotated transcripts in the T4 and T5 neurons. Overall design: Cell type – specific transcriptome analysis of the RNA isolated from immunoprecipitated nuclei, performed in two biological replicates
Publication Title
RNA-Seq Transcriptome Analysis of Direction-Selective T4/T5 Neurons in Drosophila.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The generation of induced pluripotent stem cells (iPSCs) from differentiated cells following forced expression of Oct4, Klf4, Sox2 and c-Myc (OKSM) is slow and inefficient, suggesting that transcription factors have to overcome somatic barriers that resist cell fate change. Here, we performed an ubiased serial shRNA enrichment screen to identify novel repressors of somatic cell reprogramming into iPSCs. This effort uncovered the sumoylation effector protein Sumo2 as one of the strongest roadblocks to iPSC formation. Depletion of Sumo2 both enhances and accelerates reprogramming, yielding transgene-independent, chimera-competent iPSCs after as little as 36 hours of OKSM expression. We further show that the Sumo2 pathway acts independently of exogenous c-Myc expression and in parallel with small molecule enhancers of reprogramming. Critically, suppression of SUMO2 also promotes the generation of human iPSCs. Together, our results reveal sumoylation as a crucial post-transcriptional mechanism that resists the acquisition of pluripotency from fibroblasts using defined factors.
Publication Title
A Serial shRNA Screen for Roadblocks to Reprogramming Identifies the Protein Modifier SUMO2.
Sample Metadata Fields
Sex, Specimen part, Time
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