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GSE15143
Gallus gallus
6 Downloadable Samples
Affymetrix Chicken Genome Array (chicken)
Description
Fibrotic diseases are a group of pathologies with high incidence and mortality. Despite extensive research efforts, efficient therapies are still not available. Understanding the molecular mechanisms driving the onset, progression and possible resolution of fibrosis is a prerequisite to the development of successful therapies. The central role of the TGF-beta pathway and myofibroblasts in the pathogenesis of fibrosis is now generally accepted. The possible mechanisms of myofibroblast elimination or dedifferentiation, on the other hand, are still almost uncharted territory. Basic fibroblast growth factor (bFGF) is able to suppress myofibroblastic differentiation of mesenchymal cells, but the underlying mechanism has not been studied in detail. Here, we show that sustained expression of the transcription factor EGR4, which is inducible by bFGF, in primary chicken embryo dermal myofibroblasts results in suppression of the myofibroblastic phenotype, characterized by the loss of smooth muscle actin fibers and a substantial reduction in the production of extracellular matrix. Detailed analysis of the possible molecular mechanisms revealed FOXG1, BAMBI, NAB1, NAB2 and DUSP5 genes forming an EGR4 regulated network counteracting autocrine TGF-beta signaling.
Publication Title
Effective myofibroblast dedifferentiation by concomitant inhibition of TGF-β signaling and perturbation of MAPK signaling.
Sample Metadata Fields
Specimen part
View Samples- Gallus gallus
- 6 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
Myofibroblast is a specific type of mesenchymal cell characterized by synthesis of extracellular matrix and contractile activity. While it serves a beneficial function during tissue wound healing under physiological conditions, it can cause devastating damage to organs afflicted with fibrosis. Myofibroblasts are also present in tumor stroma and contribute actively to tumor growth and spreading. Chicken embryo dermal myofibroblasts (CEDM) represent a novel ex vivo model suitable for the analysis of myofibroblastic phenotype as they show strongly pronounced, uniform and self-sustained myofibroblastic phenotype that is stable in time. As myofibroblastic differentiation is controlled chiefly by TGF-beta signaling, the understanding of the differentiation program entails the determination of TGF-beta-regulated genes. To achieve such a goal, we performed oligonucleotide microarray analysis of CEDM cells treated with a selective TGFBR1 kinase inhibitor. Genes reported previously to be under the control of TGF-beta signaling in mammalian cells appeared among the affected genes also in CEDM cells and many so far unknown TGF-beta targets were revealed.
Publication Title
Molecular analysis of the TGF-beta controlled gene expression program in chicken embryo dermal myofibroblasts.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Gallus gallus
- 6 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
The AMV v-Myb oncoprotein causes oncogenic transformation of myelomonocytic cells in vivo and in vitro. Its transforming capacity is strictly dependent upon the N-terminal DNA binding domain, the central transactivation region, and on the C-terminal domain containing a putative leucine zipper motif. While deletions in the central part of the leucine zipper region or point mutations of critical leucine residues abolish the leukemogenicity of the protein, a small deletion within the N-terminal part (deltaP mutant) preserves almost full in vitro transforming ability and only weakens the leukemogenic potential in vivo. We analyzed the gene expression profiles of ex vivo cultures transformed with either wild type or deltaP mutant of v-Myb. A few tens of genes were found to be significantly and reproducibly differentially expressed between the two cultures. Among them, the transcript of the CDKN2A gene, which is critically involved in the cell cycle progression regulation, showed higher expression in the deltaP mutant transformed cells. In mammals and also some avian species, there are two different mRNAs - ARF and INK4A transcribed from the CDKN2A locus. It is known that in chickens the locus had been rearranged in evolution and only one mRNA is transcribed. We found that this mRNA encodes both ARF and INK4A and that the INK4A protein translation starts with a GUG codon downstream of the ARF AUG initiation codon and proceeds in a different reading frame. INK4A protein thus exists in chicken cells as well and its negative regulation by v-Myb is a part of the leukemic transformation mechanism.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Gallus gallus
- 6 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
The neural crest (NC) is a transient dynamic structure of ectodermal origin, found in early vertebrate embryos. The multipotential NC cells migrate along well defined routes, differentiate to various cells types including melanocytes and participate in the formation of various permanent tissues. Abnormal development of NC cells causes several human diseases neurocristopathies. As there is only limited information about the molecular mechanisms controlling early events in melanocyte specification and development, we exploited the AMV v-Myb transcriptional regulator, which directs differentiation of in vitro chicken NC cells to the melanocyte lineage. This activity is strictly dependent on v-Myb specifically binding to the Myb recognition DNA element (MRE). The two tamoxifen-inducible v-myb alleles were constructed, one which recognizes the MRE and one which does not. These were activated in ex-ovo NC cells, and the expression profiles of resulting cells were analyzed using Affymetrix microarrays and RT-PCR. These approaches revealed up-regulation of the BMP antagonist gremlin 2 mRNA, and down-regulation of mRNAs encoding several epithelial genes including KRT19 as very early events following the activation of melanocyte differentiation by v-Myb.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Gallus gallus
- 4 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
Metastatic progression is the leading cause of cancer mortality yet we have an incomplete view of the genetic events governing this process. An investigation was undertaken to explore the role of homeodemain only protein X (HOPX) in metastatic propensity and to identify other genes that may participate in metastasis development. The transcription factor HOPX was assessed for its possible involvement in metastasis formation using a knock-down induced by plasmid-delivered shRNAs. We used our original model system of chicken v-src-transformed tumour cell line PR9692 and its subclone (PR9692-E9) that have lost the ability to induce metastases after inoculation into syngeneic chickens without any significant change in primary tumour formation. We found that also a PR9692 cell line with decreased expression of HOPX gene (PR9692-shHOPX) lost its metastatic capacity in vivo (in chickens) and displayed a reduced cell migration in vitro. We compared the gene expression profiles of control (PR9692-shMOCK) and PR9692-shHOPX cells using oligonucleotide microarrays, assuming that genes with differential expression might be associated with metastasis. The data were compared with a previous study showing differences in gene expression between the PR9692 and PR9692-E9 cells. Bioinformatics was applied to identify gene expression patterns associated with metastasis. 234 genes were identified to show at least 2-fold change in both pairs of cell lines. The results were validated with real-time quantitative RT-PCR and the differential expression was confirmed for several genes. We were also able to demonstrate a significant change at protein level in case of three selected genes (NCAM, FOXG1, ITGA4). shRNA mediated knockdown of one of the identified HOPX regulated genes (integrin alpha 4) in the PR9692 cell line itself showed a marked inhibition of metastasis formation.
Publication Title
Downregulation of HOPX controls metastatic behavior in sarcoma cells and identifies genes associated with metastasis.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
We examined the adherence-mediated signaling of meningococci to human cells by comparing gene expression profiles of primary human umbilical vein endothelial cells (HUVEC) infected by piliated and adherent wild-type (WT), frpC/frpA-deficient mutant, or the non-adherent (pilD) N. meningitidis MC58 bacteria defective in production of the type IV pilus, respectively. Surprisingly, no significant difference was found between the transcriptomes of HUVECs infected by bacteria producing, or not the RTX FrpC and FrpA proteins, thus failing to provide any hints on their biological activity. In contrast, pili-mediated adhesion of meningococci resulted in alterations of expression levels of human genes known to regulate apoptosis, cell proliferation, inflammatory response or adhesion. In particular, genes for signaling pathway proteins involved in early embryonic development, such as transforming growth factor- (TGF-)/Smad, Wnt/-catenin, and Notch/Jagged were found to be upregulated upon adhesion of N. meningitidis together with genes for a number of transcription factors. This reveals that adhering piliated meningocci manipulate signaling pathways controlling human cell proliferation, survival and defense mechanisms, while establishing a commensal relationship with the host.
Publication Title
Meningococcal adhesion suppresses proapoptotic gene expression and promotes expression of genes supporting early embryonic and cytoprotective signaling of human endothelial cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Oocyte maturation is accompanied by a transition from mRNA stability to instability. We investigated the role of DCP1A and DCP2, proteins responsible for mRNA decapping, in mRNA destabilization during mouse oocyte maturation.
Publication Title
Maternally recruited DCP1A and DCP2 contribute to messenger RNA degradation during oocyte maturation and genome activation in mouse.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Double-stranded RNA (dsRNA) can enter different pathways in mammalian cells, including sequence-specific RNA interference, sequence-independent interferon response and editing by adenosine deaminases. To assess the potential of expressed dsRNA to induce interferon stimulated genes in somatic cells, we performed microarray analysis of HEK293 and HeLa cells transfected with a MosIR plasmid expressing an mRNA with a long inverted repeat structure in its 3UTR (MosIR) or with a parental MosIR plasmid (without inverted repeat) as a control.
Publication Title
dsRNA expression in the mouse elicits RNAi in oocytes and low adenosine deamination in somatic cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
We analyzed a role of histone deacetylases in alternative splicing regulation. Using human exon arrays we identified a list of 683 genes whose splicing changes after HDAC inhibition with sodium butyrate.
Publication Title
Histone deacetylase activity modulates alternative splicing.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
We analyzed a role of Brd2 protein in transcription and alternative splicing. 289 genes change alternative splicing after Brd2 knockdown and 1459 genes alter gene expression compared to cells treated with negative control siRNA.
Publication Title
The C-terminal domain of Brd2 is important for chromatin interaction and regulation of transcription and alternative splicing.
Sample Metadata Fields
Cell line
View Samples