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GSE48859
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Expression of the EMT-inducing transcription factor Snail is enhanced in different human cancers. To investigate the in vivo role of Snail during progression of epithelial cancer, we used a mouse model with skin-specific overexpression of Snail. Snail transgenic mice spontaneously developed distinct histological subtypes of skin cancer, such as basal cell carcinoma, squamous cell carcinoma and sebaceous gland carcinoma. Development of sebaceous gland carcinomas strongly correlated with the direct and complete repression of Blimp-1, a central regulator of sebocyte homeostasis. Snail expression in keratinocyte stem cells significantly promotes their proliferation associated with an activated FoxM1 gene expression signature, resulting in a larger pool of Mts24-marked progenitor cells. Furthermore, primary keratinocytes expressing Snail showed increased survival and strong resistance to genotoxic stress. Snail expression in a skin-specific p53-null background resulted in accelerated formation of spontaneous tumours and enhanced metastasis. Our data demonstrate that in vivo expression of Snail results in de novo epithelial carcinogenesis by allowing enhanced survival, expansion of the cancer stem cell pool with accumulated DNA damage, a block in terminal differentiation and increased proliferation rates of tumour-initiating cells.
Publication Title
Epidermal Snail expression drives skin cancer initiation and progression through enhanced cytoprotection, epidermal stem/progenitor cell expansion and enhanced metastatic potential.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We demonstrate for the first time that the extracellular matrix glycoprotein Tenascin-C regulates the expression of key patterning genes during late embryonic spinal cord development, leading to a timely maturation of gliogenic neural precursor cells. We first show that Tenascin-C is expressed by gliogenic neural precursor cells during late embryonic development. The loss of Tenascin-C leads to a sustained generation and delayed migration of Fibroblast growth factor receptor 3 expressing immature astrocytes in vivo. Furthermore, we could demonstrate an upregulation of Nk2 transcription factor related locus 2 (Nkx2.2) and its downstream target Sulfatase 1 in vivo. A dorsal expansion of Nkx2.2-positive cells within the ventral spinal cord indicates a potential progenitor cell domain shift. Moreover, Sulfatase 1 is known to regulate growth factor signalling by cleaving sulphate residues from heparan sulphate proteoglycans. Consistent with this possibility we observed changes in both Fibroblast growth factor 2 and Epidermal growth factor responsiveness of spinal cord neural precursor cells. Taken together our data clearly show that Tenascin-C promotes the astroglial lineage progression during spinal cord development.
Publication Title
The extracellular matrix molecule tenascin C modulates expression levels and territories of key patterning genes during spinal cord astrocyte specification.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In order to assess the physiological role of Cop1 in vivo we generated mice that do no longer express the protein. Cop1KO mice die at around E10.5 of embryonic development. In order to gain insights into the molecular mechanisms that cause the embryonic death we compared the genome-wide gene expression profile of E9.5 wild-tytpe and Cop1-null embryos. The data do not support a role for Cop1 in the regulation of the p53 pathway in vivo and highlight a role for Cop1 in cardiovascular development and/or angiogenesis. The abstract of the associated publication is as follows:Biochemical data have suggested conflicting roles for the E3 ubiquitin ligase Cop1 in tumourigenesis. Here we present the first in vivo investigation of the role of Cop1 in cancer aetiology. We used an innovative genetic approach to generate an allelic series of Cop1 and show that Cop1 hypomorphic mice spontaneously develop malignancy at a high frequency in their first year of life and are highly susceptible to radiation-induced lymphomagenesis. Biochemically, we show that Cop1 regulates c-Jun oncoprotein stability and modulates c-Jun/AP1 transcriptional activity in vivo. Cop1-deficiency stimulates cell proliferation in a c-Jun-dependent manner. We conclude that Cop1 is a tumour suppressor that antagonizes c-Jun oncogenic activity in vivo.
Publication Title
Cop1 constitutively regulates c-Jun protein stability and functions as a tumor suppressor in mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Hematopoietic stem and progenitor cells acquire distinct DNA-hypermethylation during in vitro culture.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Hematopoietic stem and progenitor cells (HPCs) can be maintained in vitro, but the vast majority of their progeny loses stemness during culture. We have analyzed DNA methylation (DNAm) profiles of freshly isolated CD34+ cells and upon expansion on either tissue culture plastic (TCP) or mesenchymal stromal cells (MSCs). Cultured HPCs acquired significant DNA-hypermethylation, particularly in up-stream promoter regions and shore-regions of CpG islands (CGIs). To analyze if these DNAm changes are relevant for differential gene expression we analyzed gene expression profiles of additional samples. As expected highly expressed genes (10% with highest signal intensity in gene expression arrays) were hardly methylated at promoter regions, CGIs and shore-regions.
Publication Title
Hematopoietic stem and progenitor cells acquire distinct DNA-hypermethylation during in vitro culture.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Epigenetic rejuvenation of mesenchymal stromal cells derived from induced pluripotent stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Macrophage activation by bacterial lipopolysaccharides (LPS) is induced through Toll-like receptor 4 (TLR4). The synthesis and activity of TLR4 downstream signalling molecules modulates the expression of pro- and anti-inflammatory cytokines. To address the impact of post-transcriptional regulation on that process, we performed RIP-Chip analysis. Differential association of mRNAs with heterogeneous ribonucleoprotein K (hnRNP K), an mRNA-specific translational regulator in differentiating haematopoietic cells, was studied in non-induced and LPS-activated macrophages. Analysis of interactions affected by LPS revealed an enrichment of mRNAs encoding TLR4 downstream kinases and their modulators. We focused on transforming growth factor activated kinase-1 (TAK1), a central player in TLR4 signalling. HnRNP K interacts specifically with a sequence in the TAK1 mRNA 3' UTR in vitro. Silencing of hnRNP K does not affect TAK1 mRNA synthesis and stability, but enhances TAK1 mRNA translation, resulting in elevated TNF-alpha, IL-1beta and IL-10 mRNA expression. Our data suggest that the hnRNP K-3' UTR complex inhibits TAK1 mRNA translation in non-induced macrophages. LPS-dependent TLR4 activation abrogates translational repression and newly synthesised TAK1 initiates the inflammatory response of macrophages.
Publication Title
Translation control of TAK1 mRNA by hnRNP K modulates LPS-induced macrophage activation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Standardization of mesenchymal stromal cells (MSCs) remains a major obstacle in regenerative medicine. Starting material and culture expansion affect cell preparations and render comparison between studies difficult. In contrast, induced pluripotent stem cells (iPSCs) assimilate towards a ground-state and may therefore give rise to more standardized cell preparations. We reprogrammed bone marrow MSCs into iPSCs which were subsequently re-differentiated towards MSCs. These iPS-MSCs revealed similar morphology, immunophenotype, in vitro differentiation potential, and gene expression profiles as primary MSCs. DNA methylation (DNAm) profiles of iPSCs maintained some donor-specific characteristics, whereas tissue-specific, senescence-associated, and age-related DNAm patterns were erased during reprogramming. iPS-MSCs reacquired senescence-associated DNAm during culture expansion but they remained rejuvenated with regard to age-related DNAm. Overall, iPS-MSCs and MSCs are similar in function but differ in their epigenetic makeup.
Publication Title
Epigenetic rejuvenation of mesenchymal stromal cells derived from induced pluripotent stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
Co-treatment with soluble CD74 and MIF induced necroptosis in cardiac myofibroblasts. The underlying mechanism of sCD74/MIF-induced necroptosis are still unkown. We used a microarray to identify pathways regulated by co-treatment with sCD74 and MIF .
Publication Title
Soluble CD74 Reroutes MIF/CXCR4/AKT-Mediated Survival of Cardiac Myofibroblasts to Necroptosis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Neuromedin U (NMU), which is thought to contribute to putative metastasis processes in various tumor entities, was identified as being up-regulated in breast cancer. Therefore, we aimed to uncover the role of NMU in breast cancer subtypes deciphering for the first time NMU-driven signalling pathways and downstream targets.
Publication Title
Oncogenic features of neuromedin U in breast cancer are associated with NMUR2 expression involving crosstalk with members of the WNT signaling pathway.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Race
View Samples