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GSE28634
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
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
- 9 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
A model of tumor metastasis based on v-src transformed immortalized cell lines was developed. The model consists of highly metastatic PR9692 cell line and a derived clone PR9692-E9 which has lost the metastatic abilities. Introduction of exogenous EGR1 gene into the non-metastasizing PR9692-E9 cells completely restores the metastatic potential. Revealed changes in gene expression provide insight into the molecular mechanisms contolling metastatic behavior of sarcoma cells.
Publication Title
The transcription factor EGR1 regulates metastatic potential of v-src transformed sarcoma cells.
Sample Metadata Fields
Cell line
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- Caenorhabditis elegans
- 6 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
NCoR and SMRT are two paralogous vertebrate proteins that function as corepressors with unliganded nuclear receptors. Although C. elegans has a large number of nuclear receptors, orthologues of the corepressors NCoR and SMRT have not unambiguously been identified in Drosophila or C. elegans. Here, we identify GEI-8 as the closest homologue of NCoR and SMRT in C. elegans and demonstrate that GEI-8 is expressed as at least two isoforms throughout development in multiple tissues, including neurons, muscle and intestinal cells. We demonstrate that a homozygous deletion within the gei-8 coding region, which is predicted to encode a truncated protein lacking the predicted NR domain, results in severe mutant phenotypes with developmental defects, slow movement and growth, arrested gonadogenesis and defects in cholinergic neurotransmission. Whole genome expression analysis by microarrays identified sets of de-regulated genes consistent with both the observed mutant phenotypes and a role of GEI-8 in regulating transcription. Interestingly, the upregulated transcripts included a predicted mitochondrial sulfide:quinine reductase encoded by Y9C9A.16. This locus also contains non-coding, 21-U RNAs of the piRNA. Inhibition of the expression of the region coding for 21-U RNAs leads to irregular gonadogenesis in the homozygous gei-8 mutants, but not in an otherwise wild-type background, suggesting that GEI-8 may function in concert with the 21-U RNAs to regulate gonadogenesis. Our results confirm that GEI-8 is the orthologue of the vertebrate NCoR/SMRT corepressors and demonstrate important roles for this putative transcriptional corepressor in development and neuronal function.
Publication Title
GEI-8, a homologue of vertebrate nuclear receptor corepressor NCoR/SMRT, regulates gonad development and neuronal functions in Caenorhabditis elegans.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
NHR-23, a conserved member of the nuclear receptor family of transcription factors, is required for normal development in C. elegans where it plays a critical role in growth and molting. In a search for NHR-23 dependent genes, we performed whole genome comparative expression microarrays on both control and nhr-23 inhibited synchronized larvae. Genes that decreased in response to nhr-23 RNAi included several collagen genes. Unexpectedly, several hedgehog-related genes were also down-regulated after nhr-23 RNAi. A homozygous nhr-23 deletion allele was used to confirm the RNAi knockdown phenotypes and the changes in gene expression. Our results indicate that NHR-23 is a critical coregulator of functionally linked genes involved in growth and molting and reveal evolutionary parallels among the ecdysozoa.
Publication Title
NHR-23 dependent collagen and hedgehog-related genes required for molting.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Polycomb group (PcG) proteins play a pivotal role in silencing developmental genes and help to maintain various stem and precursor cells and regulate their differentiation. PcG factors also regulate dynamic and complex regional specification, particularly in mammals, but this activity is mechanistically not well understood. In this study, we focused on proximal-distal (PD) patterning of the mouse forelimb bud to elucidate how PcG factors contribute to a regional specification process that depends on developmental signals. Depletion of the RING1 proteins RING1A (RING1) and RING1B (RNF2), which are essential components of Polycomb repressive complex 1 (PRC1), led to severe defects in forelimb formation along the PD axis. We show that preferential defects in early distal specification in Ring1A/B-deficient forelimb buds accompany failures in the repression of proximal signal circuitry bound by RING1B, including Meis1/2, and the activation of distal signal circuitry in the prospective distal region. Additional deletion of Meis2 induced partial restoration of the distal gene expression and limb formation seen in the Ring1A/B-deficient mice, suggesting a crucial role for RING1-dependent repression of Meis2 and likely also Meis1 for distal specification. We suggest that the RING1-MEIS1/2 axis is regulated by early PD signals and contributes to the initiation or maintenance of the distal signal circuitry.
Publication Title
RING1 proteins contribute to early proximal-distal specification of the forelimb bud by restricting Meis2 expression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Polycomb group (PcG) proteins play a pivotal role in silencing of development-related genes and contribute to maintain various stem and precursor cells and regulate their differentiation. However, it is not well understood how PcG factors regulate dynamic and complex morphogenetic processes particularly in mammals. In this study, we focused on proximal-distal (PD) patterning of forelimb bud to elucidate how PcG factors contribute to regulation of morphogenetic processes that depends on developmental signals. Depletion of RING1 proteins, which are common components of both canonical and variant Polycomb repressive complex-1 (PRC1), led to dramatic deficiencies in forelimb formation.
Publication Title
RING1 proteins contribute to early proximal-distal specification of the forelimb bud by restricting Meis2 expression.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
IlluminaHiSeq2000
Description
Some of the functions and mechanisms of PPAR?-mediated regulation of vascular homeostasis have been revealed, the potential role of PPAR? in angiogenesis is obscure. In human ECs, PPAR?-deficiency was studied using siRNA strategy and RNA sequencing was utilized to reveal angiogenesis-associated targets for PPARg. Overall design: Our aim is to reveal the possible role of PPARy in angiogenesis.
Publication Title
Loss of PPARγ in endothelial cells leads to impaired angiogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 1000
Description
Using wild type and Ash1l deltaSET mutant embryonic stem cells, here we report differences of gene expression pattern under undifferentiated state and differentiated state. Interestingly, gene expression changes are frequently observed in a subset of gene group that is regulated by Polycomb group proteins. Overall design: Examination of 2 cell types in 2 different conditions.
Publication Title
Ash1l methylates Lys36 of histone H3 independently of transcriptional elongation to counteract polycomb silencing.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples