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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
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GSE349- Homo sapiens
- 14 Downloadable Samples
Affymetrix Human Genome U95 Version 2 Array (hgu95av2), Affymetrix Human Genome U95A Array (hgu95a)
Description
These patients proved resistant to docetaxel treatment, exhibiting residual tumor of 25% or greater remaining volume.
Publication Title
Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer.
Sample Metadata Fields
No sample metadata fields
View Samples GSE350- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
These patients were sensitive to docetaxel treatment, exhibiting less than 25% residual tumor.
Publication Title
Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer.
Sample Metadata Fields
No sample metadata fields
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- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2), Affymetrix Human Genome U95A Array (hgu95a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Patterns of resistance and incomplete response to docetaxel by gene expression profiling in breast cancer patients.
Sample Metadata Fields
No sample metadata fields
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- Mus musculus
- 43 Downloadable Samples
- Illumina HiSeq 2000
Description
Since the first generation of induced Pluripotent Stem cells (iPSCs), several reprogramming systems have been used to study its molecular mechanisms. However, the system of choice largely affects the reprogramming efficiency, influencing our view on the mechanisms. Here we demonstrate that reprogramming triggered by less efficient polycistronic reprogramming cassettes not only highlights Mesenchymal-Epithelial Transition (MET) as a roadblock, but also faces more severe difficulties to attain a pluripotent state even post-MET. Also, in contrast to previous findings, more efficient cassettes can reprogram both wild type and Nanog-/- fibroblasts with comparable efficiencies, routes and kinetics, rebutting previous studies that Nanog is critical for iPSC generation. We revealed that the 9 amino acids in the N-terminus of Klf4 in polycistronic reprogramming cassettes are the dominant factor causing these critical differences. Our data establishes that some reprogramming roadblocks are system-dependent, highlighting the need to pursue mechanistic studies with close attention to the systems to better understand reprogramming. Overall design: The aim of the experiment is to compare the reprogramming pathways driven by two different polycistronic cassettes (MKOS and OKMS). We have isolated cells at intermediate stages of both MKOS and OKMS reprogramming and analysed their gene expression profiles. 2N- are CD44- ICAM1-, Nanog-GFP-, 3N- are CD44- ICAM1+, Nanog-GFP-, 3N+ are CD44- ICAM1+, Nanog-GFP+, all from day 10 of reprogramming. MKOS/OKMS iPSCs are established iPSC clones, TNG an Embryonic Stem Cell line carrying a Nanog-GFP reporter published in Chambers et al. Cell, 113, 643-655, from this line TNG MKOS and OKMS Embryonic Stem Cells were generated after targeting the Sp3 locus with the MKOS or the OKMS cassette respectively,E14 a reference Embryonic Stem Cell line and MEF are Mouse Embryonic Fibroblasts either wild type or generaterd from TNG MKOS or OKMS ESCs. D6 is the D6s4B5 iPSC line published in O''Malley et al. Nature, 499, 88-91.
Publication Title
Reprogramming Roadblocks Are System Dependent.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
We report the expression profiles of MCF10A cells encapsulated in hydrogels of varying stiffness and composition. Cells were encapsulated for 7 days in either 1.) soft alginate and reconstituted basement membrane (rBM), 2.) stiff alginate and rBM, 3,) soft col-1 and rBM, or 4.) stiff col-1. We find global gene expression changes in response to enhanced ECM stiffness, independent of expression changes in response to col-1 exposure. These results provide a comprehensive study of the gene expression changes associated with increased ECM stiffness in addition to the gene expression changes associated with increased col-1 concentration in combination with, and independent of, ECM stiffness. Overall design: Expression profiling of MCF10A cells in four hydrogel conditions were sequenced in duplicate via Illumina HiSeq.
Publication Title
YAP-independent mechanotransduction drives breast cancer progression.
Sample Metadata Fields
Specimen part, Cell line, Subject
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