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Platform
GSE57281
Homo sapiens
12 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
RNA helicases DDX5 and DDX17 are members of a large family of highly conserved proteins involved in gene expression regulation, although their in vivo targets and activities in biological processes like cell differentiation, that requires reprogramming of gene expression programs at multiple levels, are not well characterized. In this report, we uncovered a new mechanism by which DDX5 and DDX17 cooperate with hnRNP H/F splicing factors to define epithelial- and myoblast-specific splicing subprograms. We next observed that downregulation of DDX5 and DDX17 protein expression during epithelial to mesenchymal transdifferentiation and during myogenesis contributes to switching splicing programs during these processes. Remarkably, this downregulation is mediated by the production of microRNAs induced upon differentiation in a DDX5/DDX17-dependent manner. Since DDX5 and DDX17 also function as coregulators of master transcriptional regulators of differentiation, we propose to name these proteins master orchestrators of differentiation, that dynamically orchestrate several layers of gene expression.
Publication Title
RNA helicases DDX5 and DDX17 dynamically orchestrate transcription, miRNA, and splicing programs in cell differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Malat1 is not an essential component of nuclear speckles in mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Malat1 is an abundant long noncoding RNA that localizes to nuclear bodies known as nuclear speckles, which contain a distinct set of pre-mRNA processing factors. Previous in vitro studies have demonstrated that Malat1 interacts with pre-mRNA splicing factors, including the serine- and arginine-rich (SR) family of proteins, and regulates a variety of biological processes, including cancer cell migration, synapse formation, cell cycle progression, and responses to serum stimulation. To address the physiological function of Malat1 in a living organism, we generated Malat1-KO (KO) mice using homologous recombination. Unexpectedly, the Malat1-KO mice were viable and fertile, showing no apparent phenotypes. Nuclear speckle markers were also correctly localized in cells that lacked Malat1. However, the cellular levels of another long noncoding RNA, Neat1, which is an architectural component of nuclear bodies known as paraspeckles, were downregulated in a particular set of tissues and cells lacking Malat1.
Publication Title
Malat1 is not an essential component of nuclear speckles in mice.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 32 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Rhabdomyosarcoma is a pediatric malignancy thought to arise from the uncontrolled proliferation of myogenic cells. Here, we have generated models of rhabdomyosarcoma in the zebrafish by inducing oncogenic KRASG12D expression at different stages during muscle development. Several zebrafish promoters were used including the cdh15 and rag2 promoters that drive gene expression in early muscle progenitors, and the mylz2 promoter that expresses in differentiating myoblasts. The tumors that developed differed in their ability to recapitulate normal myogenesis. cdh15:KRASG12D and rag2:KRASG12D fish developed tumors that displayed an inability to fully undergo muscle differentiation by histologic appearance and gene expression analyses. In contrast, mylz2:KRASG12D tumors more closely resembled mature skeletal muscle and were most similar to well-differentiated human rhabdomyosarcoma by gene expression. mylz2:KRASG12D fish showed significantly improved survival compared to cdh15:KRASG12D and rag2:KRASG12D fish. Tumor-propagating activity was enriched in myf5-expressing cell populations within all of the tumor types. Our results demonstrate that oncogene expression at different stages during muscle development has profound effects on the ability of tumor cells to recapitulate normal myogenesis, altering the tumorigenic capability of these cells.
Publication Title
Zebrafish rhabdomyosarcoma reflects the developmental stage of oncogene expression during myogenesis.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 9 Downloadable Samples
- Zebrafish Gene 1.0 ST Array (zebgene10st)
Description
Key regulators of septum formation between the left and right ventricle in mammals, including the transcription factors TXB5 and PITX2, feature loss-of-function phenotypes that affect development of the two-chambered zebrafish heart, suggesting
Publication Title
Generating and evaluating a ranked candidate gene list for potential vertebrate heart field regulators.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 18 Downloadable Samples
- Zebrafish Gene 1.0 ST Array (zebgene10st)
Description
The zebrafish is a powerful model for the study of hematopoietic stem and progenitor cells (HSPC). We have developed a novel HSPC-specific transgenic line (Runx1+23:GFP). We have used this line in time-lapse live imaging studies to track the migration of HSPC during development. We have also performed a chemical genetic screen to find small molecules that modulate HSPC numbers during development. Treating embryos from 2-3 days post fertilization (2-3 dpf) then fixing for in situ staining with HSPC probes cmyb and runx1, we found the compound lycorine increased HSPC numbers. Applying this compound during time-lapse live imaging showed increased accumulation of Runx+ HSPC in the caudal hematopoietic tissue (CHT). Treatment from 2-3 dpf, then washing off the compound, had a sustained effect on the size of the HSPC with Runx+ numbers higher at 5 and 7 dpf.
Publication Title
Hematopoietic stem cell arrival triggers dynamic remodeling of the perivascular niche.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Activation or maintenance of a leukemia stem cell self-renewal pathway in downstream myeloid cells is an important component of AML development
Publication Title
The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 8 Downloadable Samples
IlluminaHiSeq2500
Description
Goal of this study is differential gene expression between wild type and Toddler mutant during early zebrafish embryogenesis Overall design: Four timepoints - 4 hours post fertilization (hpf), 5 hpf, 6 hpf, and 7 hpf; one replicate of wild type at each time point, one replicate Toddler mutant at each time point
Publication Title
Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We aimed to investigate the function of syndecan-1 in tumor cell adhesion and migration, with special focus on the importance of its distinct protein domains, to better understand the structure-function relationship of syndecan-1 in tumor progression. We utilized two mesenchymal tumor cell lines which were transfected to stably overexpress full-length syndecan-1 or truncated variants: the 78 which lacks the extracellular domain except the DRKE sequence proposed to be essential for oligomerization, the 77 which lacks the whole extracellular domain, and the RMKKK which serves as a nuclear localization signal. Various bioassays for cell adhesion, chemotaxis, random movement and wound healing were studied. Furthermore we performed gene microarray to analyze the global gene expression pattern influenced by syndecan-1.
Publication Title
Novel genes and pathways modulated by syndecan-1: implications for the proliferation and cell-cycle regulation of malignant mesothelioma cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The transcriptomic responses of syndecan-1 silencing in a human mesothelioma cell line was followed with microarray analysis. To project the transcriptome analysis on the full-dimensional picture of cellular regulation, we applied a novel method of network enrichment analysis which elucidated signalling relations between differentially expressed genes and pathways acting via various molecular mechanisms.
Publication Title
Novel genes and pathways modulated by syndecan-1: implications for the proliferation and cell-cycle regulation of malignant mesothelioma cells.
Sample Metadata Fields
Cell line
View Samples