Filters
Technology
Platform
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The transcription factor Evi1 is essential for the formation and maintenance of hematopoietic stem cells, and induces clonal dominance with malignant progression upon constitutive activation by chromosomal rearrangements or transgene integration events. To understand the immediate and adaptive response of primary murine hematopoietic cells to the transcriptional upregulation of Evi1, we developed an inducible lentiviral vector system with a robust expression switch. We found that Evi1 delays differentiation and promotes survival in myeloid culture conditions, orchestrating a battery of genes involved in stemness (Aldh1a1, Ly6a [Sca1], Abca1, Epcam, among others). Importantly, Evi1 suppresses Cyclins and Cyclin-dependent kinases (Cdk), while it upregulates Cdk inhibitors, inducing quiescence in various proliferation-inducing cytokine conditions and operating in a strictly dose-dependent manner. Hematopoietic cells with persisting Evi1-induction tend to adopt a relatively low expression level. We thus classify Evi1 as a dormancy-inducing oncogene, likely requiring epigenetic and genetic compensation for cell expansion and malignant progression.
Publication Title
Activation of Evi1 inhibits cell cycle progression and differentiation of hematopoietic progenitor cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The transcription factor Evi1 is essential for the formation and maintenance of hematopoietic stem cells, and induces clonal dominance with malignant progression upon constitutive activation by chromosomal rearrangements or transgene integration events. To understand the immediate and adaptive response of primary murine hematopoietic cells to the transcriptional upregulation of Evi1, we developed an inducible lentiviral vector system with a robust expression switch. We found that Evi1 delays differentiation and promotes survival in myeloid culture conditions, orchestrating a battery of genes involved in stemness (Aldh1a1, Ly6a [Sca1], Abca1, Epcam, among others). Importantly, Evi1 suppresses Cyclins and Cyclin-dependent kinases (Cdk), while it upregulates Cdk inhibitors, inducing quiescence in various proliferation-inducing cytokine conditions and operating in a strictly dose-dependent manner. Hematopoietic cells with persisting Evi1-induction tend to adopt a relatively low expression level. We thus classify Evi1 as a dormancy-inducing oncogene, likely requiring epigenetic and genetic compensation for cell expansion and malignant progression.
Publication Title
Activation of Evi1 inhibits cell cycle progression and differentiation of hematopoietic progenitor cells.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE2172- Mus musculus
- 8 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Abstract: Interleukin-10-deficient (Il10-/-) mice serve as a model for inflammatory bowel disease (IBD). The severity of colitis strongly depends on the inbred strain carrying the disrupted Il10 gene: C3H/HeJBir (C3) confers disease susceptibility, whereas C57BL/6J (B6) confers resistance. Genome-wide scans with microsatellite markers on segregrating backcross and F2 populations resulted in the detection of ten colitogenic quantitative trait loci (QTL). The aim of this study was to reduce the large number of candidate genes within the QTL intervals by identifying those genes which are located within the candidate gene intervals and which are differentially expressed in the colon of IBD-susceptible and -resistant strains. Using this combination of QTL mapping and microarray analysis, we identified 16 genes which were differentially expressed between B6- and C3-Il10-/- mice and were located within the candidate gene intervals. Three of these genes (Pla2g2a, Gbp1, Cd14) showed prominent differences in expression levels between B6- and C3-Il10-/- as well as between B6 and C3 wildtype mice and were considered to be major candidate genes. Pla2g2a and Gbp1 are known to be polymorphic between C3 and B6 mice. Expression data for Cd14 were confirmed by real-time RT PCR using specified pathogen free and germfree Il10-/- mice. In conclusion, the large number of candidate genes was reduced to three major candidates by using a combination of QTL mapping and microarray analysis. All three genes play an important role in inflammatory processes and immune response.
Publication Title
Cd14, Gbp1, and Pla2g2a: three major candidate genes for experimental IBD identified by combining QTL and microarray analyses.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Recently, the p53-miR-34a network was identified to play an important role in tumorigenesis. As in acute myeloid leukemia with complex karyotype (CK-AML) TP53 alterations are the most common known molecular lesion, we further analyzed the p53-miR-34a axis in CK-AML with known TP53 status. Clinically, low miR-34a expression and TP53 alterations predicted for chemotherapy resistance and inferior outcome. Notably, in TP53unaltered CK-AML high miR-34a expression predicted for inferior overall survival (OS), whereas in TP53biallelic altered CK-AML high miR-34a expression pointed to better OS.
Publication Title
Altered miRNA and gene expression in acute myeloid leukemia with complex karyotype identify networks of prognostic relevance.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Uniparental parthenotes are considered an unwanted byproduct of in vitro fertilization. In utero parthenote development is severely compromised by defective organogenesis and in particular by defective cardiogenesis. Although developmentally compromised, apparently pluripotent stem cells can be derived from parthenogenetic blastocysts. Here we hypothesized that nonembryonic parthenogenetic stem cells (PSCs) can be directed toward the cardiac lineage and applied to tissue-engineered heart repair. We first confirmed similar fundamental properties in murine PSCs and embryonic stem cells (ESCs), despite notable differences in genetic (allelic variability) and epigenetic (differential imprinting) characteristics. Haploidentity of major histocompatibility complexes (MHCs) in PSCs is particularly attractive for allogeneic cell-based therapies. Accordingly, we confirmed acceptance of PSCs in MHC-matched allotransplantation. Cardiomyocyte derivation from PSCs and ESCs was equally effective. The use of cardiomyocyte-restricted GFP enabled cell sorting and documentation of advanced structural and functional maturation in vitro and in vivo. This included seamless electrical integration of PSC-derived cardiomyocytes into recipient myocardium. Finally, we enriched cardiomyocytes to facilitate engineering of force-generating myocardium and demonstrated the utility of this technique in enhancing regional myocardial function after myocardial infarction. Collectively, our data demonstrate pluripotency, with unrestricted cardiogenicity in PSCs, and introduce this unique cell type as an attractive source for tissue-engineered heart repair.
Publication Title
Parthenogenetic stem cells for tissue-engineered heart repair.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
WNT-induced secreted protein 1 (WISP1/CCN4), a member of the CCN protein family, acts as a downstream factor of the canonical WNT-signaling pathway. A dysregulated expression of WISP1 often reflects its oncogenic potential by inhibition of apoptosis, a necessary form of cell death that protect cell populations for transformation into malignant phenotypes. WISP1-signaling is also known to affect proliferation and differentiation of human mesenchymal stem cells (hMSCs), which are fundamental for the constitution and maintenance of the musculoskeletal system. Our study emphasizes the importance of WISP1-signaling for cell survival of primary human cells. Therefore, we established a successful down-regulation of endogenous WISP1 transcripts through gene silencing in hMSCs. We were able to demonstrate the consequence of cell death immediately after WISP1 down-regulation took place. Bioinformatical analyses of subsequent performed microarrays from WISP1 down-regulated vs. control samples confirmed this observation. We uncovered several clusters of differential expressed genes important for cellular apoptosis induction and immuno-regulatory processes, thereby indicating TRAIL-induced and p53-mediated apoptosis as well as IFNbeta-signaling. Since all of them act as potent inhibitors for malignant cell growth, in vitro knowledge about the connection with WISP1-signaling could help to find new therapeutic approaches concerning cancerogenesis and tumor growth in musculoskeletal tissues.
Publication Title
WISP 1 is an important survival factor in human mesenchymal stromal cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this study we analyzed the myeloma cell contact-mediated changes on the transcriptome of skeletal precursor cells. Therefore, human mesenchymal stem cells (MSC) and osteogenic precursor cells (OPC) were co-cultured with the representative myeloma cell line INA-6 for 24 h. Afterwards, MSC and OPC were separated from INA-6 cells by fluorescence activated cell sorting. Total RNA of MSC and OPC fractions was used for whole genome array analysis.
Publication Title
Contact of myeloma cells induces a characteristic transcriptome signature in skeletal precursor cells -Implications for myeloma bone disease.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage
View Samples- Danio rerio
- 6 Downloadable Samples
IlluminaHiSeq2500
Description
We sequenced mRNA from livers of 7 dpf transgenic zebrafish overexpressing foxn3 (in the liver) and non-transgenic siblings Overall design: Examination of the changes in level of different mRNAs in foxn3 transgenic and wild type siblings
Publication Title
FOXN3 Regulates Hepatic Glucose Utilization.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 73 Downloadable Samples
- IlluminaHiSeq2000
Description
Gene expression analysis of purified hematopoietic stem and progenitor cells isolated from low to intermediate risk MDS patients and age-matched normal healthy controls. Overall design: Analysis of lineage associated genes and PCA clustering of populations
Publication Title
Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The Hippo pathway is an emerging signaling cascade involved in the regulation of organ size control. It consists of evolutionally conserved protein kinases that are sequentially phosphorylated and activated. The active Hippo pathway subsequently phosphorylates a transcription coactivator, YAP, which precludes its nuclear localization and transcriptional activation. Identification of transcriptional targets of YAP in diverse cellular contexts is therefore critical to the understanding of the molecular mechanisms in which the Hippo pathway restricts tissue growth.
Publication Title
Hippo signaling regulates microprocessor and links cell-density-dependent miRNA biogenesis to cancer.
Sample Metadata Fields
Specimen part
View Samples