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SRP092906
Mus musculus
14 Downloadable Samples
Illumina HiSeq 2500
Description
Myc expression cooperates with Rb1 and Trp53 loss in mouse lungs to generate rapid, aggressive, highly metastatic and neuroendocrine-low tumors that are similar to human variant subset of SCLC with high NEUROD1 expression. Targeted drug screening reveals that mouse and human MYC-driven SCLC are vulnerable to Aurora kinase inhibition in combination with chemotherapy in vivo. Overall design: Tumor formation is induced by infecting the conditional Rb1 fl/fl; Trp53 fl/fl, LSL-Myc (T58A) and Rb1 fl/fl; Trp53 fl/fl, p130 fl/fl GEMMs with adenoviruses with Cgrp promoter driving Cre recombinase. The tumors were macro-dissected from lungs. RNA was extracted from fresh or flash frozen tumors and subjected to single end RNA sequencing.
Publication Title
MYC Drives Progression of Small Cell Lung Cancer to a Variant Neuroendocrine Subtype with Vulnerability to Aurora Kinase Inhibition.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Objective: The etiology of PCOS is mostly unknown. Existing data support both genetic and environmental factors in its pathogenesis. Design: Prospective case - control study. Setting: University Hospital. Patients: 25 patients undergoing IVF-ICSI treatment. Intervention: Genome-wide oligonucleotide microarray technology was used to study differential gene-expression patterns of cultured human cumulus cells from IVF patients divided into 4 groups according to disease state (PCOS vs. Control) and BMI (Obese vs. Lean). Results: Two differential PCOS gene expression profiles were established: Lean-Type was formed by comparing PCOS lean (PL) vs. non-PCOS lean (NL) individuals; Obese-Type was formed by comparing PCOS obese (PO) vs. non-PCOS (NO) obese patients. Conclusions: Different molecular pathways are associated with PCOS in Lean and Obese individuals, as demonstrated by gene expression profiling of cumulus cells. Our findings provide insights into the molecular pathogenesis of PCOS.
Publication Title
Gene expression microarray profiles of cumulus cells in lean and overweight-obese polycystic ovary syndrome patients.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Stress granules are small RNA-protein granules that modify the translational landscape during cellular stress to promote survival. The RhoGTPase RhoA is implicated in the formation of RNA stress granules. Our data demonstrate that the cytokinetic proteins ECT2 and AurkB are localized to stress granules in human astrocytoma cells. AurkB and its downstream target histone-3 are phosphorylated during arsenite-induced stress. Chemical (AZD1152-HQPA) and siRNA inhibition of AurkB results in fewer and smaller stress granules when analyzed utilizing high throughput fluorescent based cellomics assays. RNA immunoprecipitation with the known stress granule aggregates TIAR and G3BP1 was performed on astrocytoma cells and subsequent analysis revealed that astrocytoma stress granules harbour unique mRNAs for various cellular pathways including cellular migration, metabolism, translation and transcriptional regulation. Human astrocytoma cell stress granules contain mRNA that are known to be involved in glioma signaling and the mTOR pathway. These data provide evidence that RNA stress granules are a novel form of epigenetic regulation in astrocytoma cells, which may be targetable by chemical inhibitors and enhance astrocytoma susceptiblity to conventional therapy such as radiation and chemotherapy.
Publication Title
Epithelial Cell Transforming 2 and Aurora Kinase B Modulate Formation of Stress Granule-Containing Transcripts from Diverse Cellular Pathways in Astrocytoma Cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Screening small molecules and drugs for activity to modulate alternative splicing, we found that amiloride, distinct from four other intracellular pH-affecting analogues, could normalize the splicing of BCL-X, HIPK3 and RON/MISTR1 transcripts in human hepatocellular carcinoma Huh-7 cells. To elucidate the underlying mechanisms, our proteomic analyses of amiloride-treated cells detected hypo-phosphorylation of splicing factor SF2/ASF and also decreased levels of SRp20 and two un-identified SR proteins. We further observed decreased phosphorylation of AKT, ERK1/2 and PP1, while increased phosphorylation of p38 and JNK, suggesting that amiloride treatment down-regulated kinases and up-regulated phosphatases in the signal pathways known to affect the splicing factor protein phosphorylation. The amiloride effects of splicing factor protein hypo-phosphorylation andnormalizedoncogenic RNA splicing were both abrogated by pre-treatment with a PP1 inhibitor. We then performed global exon array analysis of Huh-7 cells treated with amiloride for 24 hours. Using gene array chips (Affymetrix GeneChip Human Exon 1.0 ST Array of >518000 exons of 42974 genes) for exon array analysis (set parameters of correlation coefficient 0.7, splicing index -1.585 , and log2 ratio -1.585), we found that amiloride influenced the splicing patterns of 551 genes involving at least 584 exons, which included 495 known protein-coding genes involving 526 exons, many of which play key roles in functional networks of ion transport, extracellular matrix, cytoskeletons and genome maintenance. Cellular functional analyses revealed subsequent invasion and migration defects, cell cycle disruption, cytokinesis impairment, and lethal DNA degradation in amiloride-treated Huh-7 cells. This study thus provides mechanistic underpinnings for exploiting small molecule modulation of abnormal RNA splicing for cancer therapeutics.
Publication Title
Small molecule amiloride modulates oncogenic RNA alternative splicing to devitalize human cancer cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The traditional view of hematopoiesis has been that all the cells of the peripheral blood are the progeny of a unitary homogeneous pool of hematopoietic stem cells (HSCs). Recent evidence suggests that the hematopoietic system is actually maintained by a consortium of HSC subtypes with distinct functional characteristics. We show here that myeloid-biased HSCs (My-HSCs) and lymphoid-biased (Ly-HSCs) can be purified according to their capacity for Hoechst dye efflux in combination with canonical HSC markers.
Publication Title
Distinct hematopoietic stem cell subtypes are differentially regulated by TGF-beta1.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Spinal muscular atrophy (SMA) is a neurodegenerative disease which exhibits selective motor neuron death caused by a ubiquitous deficiency of the survival motor neuron (SMN) protein. It remains unclear how the ubiquitous reduction of SMN lead to death in selective motor neuron pools. Medial motor neuron columns (MMC) are vulnerable, whereas lateral motor columns (LMC) are resistant to motor neuron death in SMA. Here we performed microarray and pathway analysis comparing cholera toxin subunit B (CTb) labeled vulnerable MMC and resistant LMC of pre-symptomatic SMA with corresponding motor neuron columns of control mice to identify pathways involved in selective motor neuron death in SMA. WT is FVB. SMN is Delta7 (SMN7;SMN2;Smn-) on a FVB background.
Publication Title
Converging Mechanisms of p53 Activation Drive Motor Neuron Degeneration in Spinal Muscular Atrophy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
Alternative splicing is a mechanism for increasing the protein variety of a limited number of genes. Studies have shown that aberrant regulations of the alternative splicing of apoptotic gene transcripts may contribute to the development of cancer. In this study, we isolated 4ß-Hydroxywithanolide E (4bHWE) from the traditional herb Physalis peruviana, and analyzed its biological effects in cancer cells. The results demonstrated that 4bHWE modulates the alternative splicing of apoptotic genes (e.g., HIPK3, SMAC/DIABLO, and SURVIVIN), changes the expression level of splicing factors (e.g., hnRNP C1/C2, ASF/SF2, SRp20, and SRp55), and induces histone tail posttranslational modifications (e.g., H3K27me1, H3K27me2, H3K36me3, and H3K79me1). Pretreatment with okadaic acid to inhibit protein phosphatase-1 could partly relieve the effects of 4bHWE on the alternative splicing of HIPK3 and SMAC/DIABLO transcripts, as well as on the dephosphorylation of ASF/SF2. Genome-wide detection of alternative splicing further indicated that several other apoptosis-related genes are also regulated by 4bHWE, including APAF1, CARP-1, and RIPK1. Moreover, we extended our study to apoptosis-associated molecules, detecting an increasing level of CASPASE-3 activity and cleavage of poly ADP-ribose polymerase in 4bHWE-induced apoptosis. Furthermore, in vivo experiments showed that the treatment of tumor-bearing mice with 4bHWE resulted in a marked decrease of tumor size and weight. Taken together, this study is the first to show that 4bHWE affects alternative splicing through the modulations of splicing factors, providing a novel view of the antitumor mechanism of 4bHWE. Overall design: Examination of the global genes with altered alternative splicing in 4bHWE-treated Huh-7 cells.
Publication Title
4β-Hydroxywithanolide E Modulates Alternative Splicing of Apoptotic Genes in Human Hepatocellular Carcinoma Huh-7 Cells.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mice lacking the beta 2 subunit (Chrnb2) of the neuronal nicotinic acetylcholine receptor display altered retinal waves and disorganized projections of the retinal ganglion cells to the lateral geniculate nucleus (LGN). mRNA populations from retinas and LGN from Chrnb2-/-and wild type (C57BL/6J) mice were compared at 4 days postnatal, when RGC segregation to the LGN begins in WT mice. Retinal mRNAs were also compared at adulthood.
Publication Title
Mouse mutants for the nicotinic acetylcholine receptor ß2 subunit display changes in cell adhesion and neurodegeneration response genes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
The study demontrates differences in the transcriptome ( both of protein coding transcripts and long non-coding RNAs) in the unilateral ureteric obstruction model of renal fibrosis. Overall design: Renal tissue was studied from animals undergoing sham operation (as controls) or right ureteric ligation. Animals were sacrificed 2 and 8 days following ligation and the right kidney tissue was examined.
Publication Title
Whole-transcriptome analysis of UUO mouse model of renal fibrosis reveals new molecular players in kidney diseases.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We demonstrate that GLUT4 up-regulation significantly increased cell migration and invasion in lower magligance head and neck cancer cell lines in vitro.
Publication Title
Glucose transporter 4 promotes head and neck squamous cell carcinoma metastasis through the TRIM24-DDX58 axis.
Sample Metadata Fields
Specimen part, Cell line
View Samples