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SRP152306
Mus musculus
6 Downloadable Samples
Illumina HiSeq 4000
Description
This study aimed to clarify the role of PRMT5 in the hematopoietic stem cell (HSC) compartment, and elucidate the functional relevance of PRMT5-mediated splicing in HSCs. We confirm the cell intrinsic requirement for PRMT5 in HSC maintenance, and present evidence suggesting that PRMT5 deficiency perturbs HSC proteostasis. Notably, we also uncover a critical role for PRMT5 in maintaining HSC genomic integrity by modulating splicing of genes involved in DNA repair; loss of which leads to unresolved DNA damage, p53 activation and rapid HSC exhaustion. Overall, these findings establish PRMT5-mediated splicing as a major determinant of HSC fate, and highlight the need to maintain an adequate level of PRMT5 activity in HSCs. Overall design: Hematopoietic stem cells (HSCs; Lineage-Sca-1+CD48-CD150+), isolated from Prmt5fl/fl or Prmt5?/? littermate- and gender-matched mice 7 days post-induction, were subjected to RNA-seq. HSCs for each independent sample were obtained from bone marrow cells pooled from two mice. Three independent samples were obtained for each group.
Publication Title
PRMT5 Modulates Splicing for Genome Integrity and Preserves Proteostasis of Hematopoietic Stem Cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Global DNA hypomethylation and DNA hypermethylation of promoter regionsincluding tumor suppressor genesare frequently detected in human cancers. Although many studies have suggested a contribution to carcinogenesis, it is still unclear whether the aberrant DNA hypomethylation observed in tumors is a consequence or a cause of cancer. We found that overexpression of Stella (also known as PGC7, Dppa3), a maternal factor required for the maintenance of DNA methylation in early embryos, induced global DNA hypomethylation and transformation in NIH3T3 cells. This hypomethylation was due to the binding of Stella to Np95 (also known as Uhrf1, ICBP90) and the subsequent impairment of Dnmt1 localization. In addition, enforced expression of Stella enhanced the metastatic ability of B16 melanoma cells through the induction of metastasis-related genes by inducing DNA hypomethylation of their promoter regions. Such DNA hypomethylation itself causes cellular transformation and metastatic ability. These data provide new insight into the function of global DNA hypomethylation in carcinogenesis.
Publication Title
Global DNA hypomethylation coupled to cellular transformation and metastatic ability.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 27 Downloadable Samples
- Ion Torrent Proton
Description
Purpose: The goals of this study are to elucidate the influence of integrin ß3 signaling on STAT1-dependnet gene expression in IFN?-treated HSCs. Methods: Wild type (WT) HSCs were cultured with or without IFN? and/or VN in the presence of stem cell factor (SCF) plus thrombopoietin (TPO). Subsequently, cultured HSC fraction (CD48- c-kit+ Sca-1+ Lineage-) were sorted, followed by mRNA sequence using Ion Proton (n>4). Moreover, to extract genes whose expression were changed via STAT1 in the presence of IFN?, mRNA profiles of STAT1-/- HSCs treated with or without IFN? were also generated by the same way. The sequence reads that passed quality filters were analyzed by CLC genomic workbench. Results: Using an optimized data analysis workflow, we mapped about 30 million sequence reads per sample to the mouse genome (build mm10) with CLC genomic workbench. Indeed, hierarchical clustering analysis showed that IFN?-treated STAT1-/- HSCs was categorized to the group including Wt HSCs cultured in the absence of IFN? rather than HSCs treated with IFN?. Furthermore, gene set enrichment analysis (GSEA) showed that STAT1-dependent upregulated gene sets were significantly enriched within genes whose expression was enhanced in HSCs treated with VN and IFN?. In contrast, integrin ß3 signaling in the absence of IFN? appears to not influence the expression of IFN?/STAT1-dependent genes, as evidenced by the observation that VN treatment was statistically and significantly independent of the enrichment of gene sets that were both up-regulated by STAT1 Conclusions: Our study represents that STAT1 plays a central role in IFN?-mediated HSC responses and integrin ß3 signaling in HSCs promotes STAT1-dependent gene expression in the presence of IFN?. Overall design: After HSCs derived from wild type (WT) and STAT1-/- mice were treated with IFNg and/or vitronectin for 5 days, mRNA profiles were generated by deep sequencing using Ion Proton system (n>4).
Publication Title
Integrin αvβ3 enhances the suppressive effect of interferon-γ on hematopoietic stem cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Our previous study using nude rats revealed that the parental JDCaP xenografts predominantly expressed full-length androgen receptor (AR) whereas the relapsed JDCaP xenografts after castration acquired AR splice variants including AR-V7 and ARv567es. To understand molecular mechanisms underlying the acquisition of AR splice variants in the JDCaP model, we performed microarray analysis using RNA samples of the xenografts without castration (Parent), the relapsed xenografts overexpressing full-length AR and AR-V7 (ARhiV7hi), and the relapsed xenografts expressing ARv567es (ARv567es).
Publication Title
The RNA helicase DDX39B and its paralog DDX39A regulate androgen receptor splice variant AR-V7 generation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 6 Downloadable Samples
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Probe Name Version), Affymetrix Human Gene 2.0 ST Array (hugene20st), Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
OVOL2 Maintains the Transcriptional Program of Human Corneal Epithelium by Suppressing Epithelial-to-Mesenchymal Transition.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 2 Downloadable Samples
- Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Probe Name Version), Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
In development, embryonic ectoderm differentiates into several lineages including neuroectoderm and surface ectoderm, through the mechanism largely unclear. Here we report that OVOL2 is required for the transcriptional program of corneal epithelium cell(CEC)s, a derivative of surface ectoderm, and it might regulates the differential transcriptional programs between the two lineages. By a functional screening, we identified transcription factors (TFs) maintaining human CECs. OVOL2 was necessary to maintain the transcriptional program in CECs, particularly through repressing expression of mesenchymal genes. OVOL2 combined with several TFs were able to activate the transcriptional program of CECs in fibroblasts, accompanied by induction of chromatin landscape. Moreover, our analysis revealed that neuroectoderm derivatives express some of mesenchymal genes. In fact, OVOL2 alone was able to induce the transcriptional program of CECs in neural progenitor cells (NPCs) through repression of mesenchymal genes as well as activation of epithelial genes. Our data suggest that the difference between the transcriptional programs of surface ectoderm-derivatives and neuroectoderm-derivatives is regulated in part by the reciprocally-repressive mechanism between epithelial and mesenchymal genes that is seen in epithelial-to-mesenchymal transition.
Publication Title
OVOL2 Maintains the Transcriptional Program of Human Corneal Epithelium by Suppressing Epithelial-to-Mesenchymal Transition.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To identify factors involved in glioma-initiating cells (GICs), we compared gene expressions between GIC-like cells and non-GICs.
Publication Title
Combination of a ptgs2 inhibitor and an epidermal growth factor receptor-signaling inhibitor prevents tumorigenesis of oligodendrocyte lineage-derived glioma-initiating cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To identify factors involved in glioma-initiating cells (GICs), we compared gene expression between GIC-like cells and non-GICs.
Publication Title
Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To identify factors involved in tumorigenicity of glioma-initiating cells (GICs), we compared gene expression in GIC-like cells with and without sox11 expression.
Publication Title
Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Schizosaccharomyces pombe
- 16 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Transition from proliferation to quiescence brings about extensive changes in cellular behavior and structure. However, genes critical for establishing and/or for maintaining quiescence are largely unknown. The fission yeast S. pombe is found as an excellent model for studying this problem, because it becomes quiescent under nitrogen starvation. Here we characterize 610 temperature-sensitive (ts) mutants, and identify 33 genes required for entry into and the maintenance of quiescence. These genes cover a broad range of cellular functions in the cytoplasm, membrane and the nucleus, encoding proteins for stress-responsive and cell cycle kinase signaling pathway, actin-bound and osmo-controlling endosome formation, RNA transcription, splicing and ribosome biogenesis, chromatin silencing, biosynthesis of lipid and ATP, cell wall and membrane morphogenesis, protein trafficking and vesicle fusion. We specifically highlight Fcp1, CTD phosphatase of RNA polymerase II, which differentially affects transcription of genes involved in quiescence and proliferation. We propose that the transcriptional role of Fcp1 is central to differentiate quiescence from proliferation.
Publication Title
Genetic control of cellular quiescence in S. pombe.
Sample Metadata Fields
No sample metadata fields
View Samples