Previously it has been shown that Id3 can act as an apoptosis-inducer gene in immortalized human keratinocytes. To further investigate the role of Id3 in the progression of skin cancer, the role of Id3 in A431 cells is investigated through ectopic induction of Id3.
Id3 induces an Elk-1-caspase-8-dependent apoptotic pathway in squamous carcinoma cells.
Specimen part, Cell line
View SamplesAnalysis of genes that were differentially expressed in MSC-derived hES cells (VUB01 and SA01) as compared to VUB01 and SA01 undifferentiated hES cells
Combined mRNA and microRNA profiling reveals that miR-148a and miR-20b control human mesenchymal stem cell phenotype via EPAS1.
No sample metadata fields
View SamplesClC-2 is a broadly expressed Cl- channel of the CLC family of Cl- channels and transporters which is abundantly expressed in brain. Here it was proposed to participate in lowering the cytoplasmic Cl- concentration of neurons, a process that establishes an inhibitory response to the neurotransmitters GABA and glycine (Staley et al., 1996). Heterozygous mutations in CLCN2 (the gene encoding ClC-2) were recently reported in a few patients with three clinically distinct forms of epilepsy (Haug et al, 2003). However, the disruption of ClC-2 in mice (ClC-2 KO mouse) did not entail epilepsy (Bösl et al., 2001; Nehrke et al., 2002) but myelin vacuolation in fiber tracts of the central nervous system. We used a gene expression profiling of the ClC-2 KO mouse in brain to identify possible disease mechanism which cause the observed myelin phenotype. As these myelin vacuolation became apparent in the fiber tracts of ClC-2 KO cerebellum at P28 and increased with age, we analysed the cerebellum of ClC-2 KO mice at different postnatal ages, before (P14) and after (P35) the KO cerebellum has been affected by myelin vacuolation.
Leukoencephalopathy upon disruption of the chloride channel ClC-2.
Sex, Age, Specimen part, Subject, Time
View SamplesIn order to identify pre-conceptional endometrial dysregulations, we compared the endometrial expression between fertile and IF and RM patients
Specific and extensive endometrial deregulation is present before conception in IVF/ICSI repeated implantation failures (IF) or recurrent miscarriages.
Sex, Specimen part
View SamplesMelasma is a commonly acquired hyperpigmentary disorder of the face, but its pathogenesis is poorly understood and its treatment remains challenging. We conducted a comparative histological study on lesional and perilesional normal skin to clarify the histological nature of melasma. Significantly, higher amounts of melanin and of melanogenesis-associated proteins were observed in the epidermis of lesional skin, and the mRNA level of tyrosinase-related protein 1 was higher in lesional skin, indicating regulation at the mRNA level. However, melanocyte numbers were comparable between lesional and perilesional skin. A transcriptomic study was undertaken to identify genes involved in the pathology of melasma. A total of 279 genes were found to be differentially expressed in lesional and perilesional skin. As was expected, the mRNA levels of a number of known melanogenesis-associated genes, such as tyrosinase, were found to be elevated in lesional skin. Bioinformatics analysis revealed that the most lipid metabolism-associated genes were downregulated in lesional skin, and this finding was supported by an impaired barrier function in melasma. Interestingly, a subset of Wnt signaling modulators, including Wnt inhibitory factor 1, secreted frizzled-related protein 2, and Wnt5a, were also found to be upregulated in lesional skin. Immunohistochemistry confirmed the higher expression of these factors in melasma lesions.
Transcriptional profiling shows altered expression of wnt pathway- and lipid metabolism-related genes as well as melanogenesis-related genes in melasma.
Specimen part
View SamplesCell purification technology combined with whole transcriptome sequencing and small molecule agonist of hematopoietic stem cell self-renewal has allowed us to identify the endothelial protein c receptor protein (EPCR) as a surface maker that defines a rare subpopulation of human cells which is highly enriched for stem cell activity in vivo. EPCR-positive cells exhibit a robust multi-lineage differentiation potential and serial reconstitution in immunocompromised mice. In culture, most if not all of the HSC activity is detected in the EPCR+ subset, arguing for the stability of this marker on the surface of cultured cells, a feature not found with more recently described markers such as CD49f. Functionally EPCR is essential for human HSC activity in vivo. Cells engineered to express low EPCR expression proliferate normally in culture but lack the ability to confer long-term reconstitution. EPCR is thus a stable marker for human HSC. Its exploitation should open new possibilities in our effort to understand the molecular bases behind HSC self-renewal. Overall design: Examining 3 cellular subsets: EPCR+, EPCRlow, EPCR- derived form CD34+CD45RA- cord blood cells after 7 day expansion in UM171
EPCR expression marks UM171-expanded CD34<sup>+</sup> cord blood stem cells.
No sample metadata fields
View SamplesWe have analyzed the variation of transcriptome of HUVECs intoxicated by the lethal toxin of Bacillus anthracis at 4 and 8 hours
Transcriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicity.
Specimen part
View SamplesRosacea is a common chronic inflammatory skin disease of unknown etiology. Our knowledge about an involvement of the adaptive immune system is very limited. We performed detailed transcriptome analysis, qRT-PCR, and quantitative immunohistochemistry on facial biopsies of rosacea patients, classified according to their clinical subtype. As controls, we used samples from healthy controls. Our study shows significant activation of the immune system in all subtypes of rosacea, characterizing erythematotelangiectatic rosacea (ETR) already as a disease with significant influx of proinflammatory cells. The T cell response is dominated by Th1/Th17-polarized immune cells, as demonstrated by significant upregulation of IFN or IL-17, for example. Chemokine expression patterns support a Th1/Th17 polarization profile of the T cell response. Macrophages and mast cells are increased in all three subtypes of rosacea, while neutrophils reach a maximum in papulopustular rosacea. Our studies also provide evidence for activation of plasma cells with significant antibody production already in ETR, followed by a crescendo pattern towards phymatous rosacea. In sum, Th1/Th17 polarized inflammation and macrophage infiltration is an underestimated hallmark in all subtypes of rosacea. Therapies directly targeting the Th1/Th17 pathway are promising candidates in the future treatment of this skin disease.
Molecular and Morphological Characterization of Inflammatory Infiltrate in Rosacea Reveals Activation of Th1/Th17 Pathways.
No sample metadata fields
View SamplesAXL is activated by its ligand GAS6 and is expressed in triple-negative breast cancer cells. We report that AXL is also detected in HER2+ breast cancer specimens where its expression correlates with poor patients' survival. Using murine models of HER2+ breast cancer, AXL, but not Gas6, was found essential for metastasis. We determined that AXL is required for intravasation, extravasation and growth at the metastatic site. AXL is expressed in HER2+ cancers displaying EMT signatures and contributes to sustain EMT in murine tumors. Interfering with AXL in patient-derived xenograft impaired TGF-ß-induced cell invasion. Lastly, pharmacological inhibition of AXL decreased the metastatic burden of mice developing HER2+ breast cancer. Our data identify AXL as a potential co-therapeutic target during the treatment of HER2+ breast cancers to limit metastasis. Overall design: Differential gene expression profile between tumor grafts of AXL-/- and AXL+/+ cells in FVB mice by RNA sequencing (Illumina HiSEq 2000)
The Receptor Tyrosine Kinase AXL Is Required at Multiple Steps of the Metastatic Cascade during HER2-Positive Breast Cancer Progression.
Specimen part, Cell line, Subject
View SamplesAXL is activated by its ligand GAS6 and is expressed in triple-negative breast cancer cells. We report that AXL is also detected in HER2+ breast cancer specimens where its expression correlates with poor patients' survival. Using murine models of HER2+ breast cancer, AXL, but not Gas6, was found essential for metastasis. We determined that AXL is required for intravasation, extravasation and growth at the metastatic site. AXL is expressed in HER2+ cancers displaying EMT signatures and contributes to sustain EMT in murine tumors. Interfering with AXL in patient-derived xenograft impaired TGF-ß-induced cell invasion. Lastly, pharmacological inhibition of AXL decreased the metastatic burden of mice developing HER2+ breast cancer. Our data identify AXL as a potential co-therapeutic target during the treatment of HER2+ breast cancers to limit metastasis. Overall design: Differential gene expression profile between MMTV-Neu tumors of AXL-/- and AXL+/+ by RNA sequencing (Illumina HiSEq 2000)
The Receptor Tyrosine Kinase AXL Is Required at Multiple Steps of the Metastatic Cascade during HER2-Positive Breast Cancer Progression.
Specimen part, Cell line, Subject
View Samples