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GSE40965
Mus musculus
28 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Recurrent somatic hotspot mutations of DICER1 appear to be clustered around each of four critical metal binding residues in the RNase IIIB domain of DICER1. This domain is responsible for cleavage of the 3 end of the 5p-miRNA strand of a pre-mRNA hairpin. To investigate the effects of these cancer-associated hotspot mutations we engineered mouse Dicer1-deficient ES cells to express wild-type and an allelic series of the mutant human DICER1 variants. Global miRNA and mRNA profiles from cells carrying the metal binding site mutations were compared to each other and wild-type human DICER1. The miRNA and mRNA profiles generated through the expression of the hotspot mutations were virtually identical, and the DICER1 hotspot mutation carrying cells were distinct from both wild-type and Dicer1-deficient cells. Further, miRNA profiles showed mutant DICER1 results in a dramatic loss in processing of mature 5p-miRNA strands but were still able to create 3p-strand miRNAs. Messenger-RNA profile changes were consistent with the loss of 5p-strand miRNAs and showed enriched expression for predicted targets of the lost 5p derived miRNAs. We therefore conclude that cancer-associated somatic hotspot mutations of DICER1, affecting any one of four metal binding residues in the RNase IIIB domain, are functionally equivalent with respect to miRNA-processing and are hypomorphic alleles, yielding a global loss in processing of mature 5p-strand miRNA. We further propose that this resulting 3p-strand bias in mature miRNA expression likely underpins the oncogenic potential of these hotspot mutations.
Publication Title
Cancer-associated somatic DICER1 hotspot mutations cause defective miRNA processing and reverse-strand expression bias to predominantly mature 3p strands through loss of 5p strand cleavage.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 27 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Tissue-specific NETs alter genome organization and regulation even in a heterologous system.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 27 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
The nuclear transmembrane proteins (NETs) NET29/TMEM120A, NET39/PPAPDC3 and NET47/TM7SF2 are able to reposition chromosomes towards/away from the nuclear envelope when overexpressed or knocked down in HT1080 cells. In this study we wanted to investigate the transcriptome changes after transfection of the full length NETs or a nucleoplasmic soluble fragment that does not localise to the nuclear envelope.
Publication Title
Tissue-specific NETs alter genome organization and regulation even in a heterologous system.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Constrained release of lamina-associated enhancers and genes from the nuclear envelope during T-cell activation facilitates their association in chromosome compartments.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Activation of T-cells induces dramatic changes in genome organisation and gene transcription. Here we identify changes in transcriptional profiles at 8h, 24h and 48 post activation
Publication Title
Constrained release of lamina-associated enhancers and genes from the nuclear envelope during T-cell activation facilitates their association in chromosome compartments.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Preeclampsia complicates more than 3% of all pregnancies in the United States and Europe. High-risk populations include women with diabetes, dyslipidemia, thrombotic disorders, hyperhomocysteinemia, hypertension, renal diseases, previous preeclampsia, twin pregnancies, and low socioeconomic status. In the latter case, the incidence may increase to 20% to 25%. Preeclampsia is a major cause of maternal and fetal morbidity and mortality. Preeclampsia is defined by systolic blood pressure of more than 140 mm Hg and diastolic blood pressure of more than 90 mm Hg after 20 weeks gestation in a previously normotensive patient, and new-onset proteinuria. Abnormal placentation associated with shallow trophoblast invasion (fetal cells from outer cell layer of the blastocyst) into endometrium (decidua) and improper spiral artery remodeling in the decidua are initial pathological steps.
Publication Title
Dysregulation of the circulating and tissue-based renin-angiotensin system in preeclampsia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Tissue-Specific Gene Repositioning by Muscle Nuclear Membrane Proteins Enhances Repression of Critical Developmental Genes during Myogenesis.
Sample Metadata Fields
Treatment, Time
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
The nuclear envelope transmembrane proteins (NETs) NET39/PPAPDC3, TMEM38A, TMEM214 and WFS1 are expressed or localise preferentially to the nuclear envelope in muscle cells. We knocked these proteins down using specific shRNAs and studied their effect in the diffentiation of the mouse C2C12 myoblast cell line.
Publication Title
Tissue-Specific Gene Repositioning by Muscle Nuclear Membrane Proteins Enhances Repression of Critical Developmental Genes during Myogenesis.
Sample Metadata Fields
Treatment, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Tumor growth and metastasis is controlled by paracrine signaling between cells of the tumor microenvironment and malignant cells. Cancer-associated fibroblasts (CAFs), are functionally important components of the tumor microenvironment. Although some steps involved in the cross-talk between these cells are known, there is still a lot that is not clear. Thus, the addition of, the consideration of microenvironment in the development of the disease, to the clinical and pathological procedures (currently admitted as the consistent value cancer treatments) could lay the foundations for the development of new treatment strategies to control the disease.
Publication Title
Functional heterogeneity of cancer-associated fibroblasts from human colon tumors shows specific prognostic gene expression signature.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Purpose: Evaluate gene expression profiles after inducing differentiation in cultured interstitial cystitis (IC) and control urothelial cells. Materials and Methods: Bladder biopsies were taken from IC patients and controls (women having surgery for stress incontinence). Primary cultures were grown in Keratinocyte Growth Medium with supplements. To induce differentiation, in some plates the medium was changed to DMEM-F12 with supplements. RNA was analyzed with Affymetrix chips. Three nonulcer IC patients were compared with three controls. Results: After inducing differentiation, 302 genes with a described function were altered at least 3-fold with p <0.01 in both IC and control cells. Functions of the162 upregulated genes included cell adhesion (e.g. claudins, occludin, cingulin); urothelial differentiation, retinoic acid pathway and keratinocyte differentiation (e.g. skin cornified envelope components). The 140 downregulated genes included genes associated with basal urothelium (e.g. p63, integrins ?4, ?5 and ?6, basonuclin 1 and extracellular matrix components), vimentin, metallothioneins and members of the Wnt and Notch pathways. Comparing IC vs. control cells after differentiation, only seven genes with a described function were altered at least 3-fold with p <0.01. PI3, SERPINB4, CYP2C8, EFEMP2 and SEPP1 were decreased in IC; AKR1C2 and MKNK1 were increased in IC. Conclusions: Differentiation-associated changes occurred in both IC and control cells. Comparing IC vs. control revealed very few differences. This study may have included IC patients with minimal urothelial deficiency and/or selected the cells that were most robust in culture. Also, the abnormal urothelium in IC may be due to post-translational changes and/or the bladder environment.
Publication Title
Differentiation associated changes in gene expression profiles of interstitial cystitis and control urothelial cells.
Sample Metadata Fields
Disease
View Samples