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GSE5417
Homo sapiens
8 Downloadable Samples
Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
We examined whether SATB1 functions as a global gene regulator in order to maintain the aggressive phenotype of the MDA-MB-231 cell line. We compared the gene expression profiles between control_shRNA-MDA-MB-231 cells, which express SATB1 at high levels, and SATB1_shRNA1-MDA-MB-231 in which the level of SATB1 was greatly downregulated by RNAi technology. This comparative studies were performed using two different platforms (Codelink and Affymetrix genechip) with two culture conditions either on plastic dish (2D) or on matrigel (3D) which allows cells to form a breast-like morphology only for non-aggressive cells.
Publication Title
SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The non-coding Xist RNA triggers silencing of one of the two female X chromosomes during X inactivation in mammals. Gene silencing by Xist is restricted to special developmental contexts found in cells of the early embryo and specific hematopoietic precursors. The absence of critical silencing factors might explain why Xist cannot silence outside these contexts. Here, we show that Xist can also initiate silencing in a lymphoma model. Using the tumor context we identify the special AT rich binding protein SATB1 as an essential silencing factor. We show that loss of SATB1 in tumor cells abrogates the silencing function of Xist. In normal female lymphocytes Xist localizes along SATB1 filaments and, importantly, forced Xist expression can relocalize SATB1 into the Xist cluster. This reciprocal influence on localization suggests a molecular interaction between Xist and SATB1. SATB1 and its close homologue SATB2 are expressed during the initiation window for X inactivation in embryonic stem cells and are recruited to surround the Xist cluster. Furthermore, ectopic expression SATB1 or SATB2 enables gene silencing by Xist in embryonic fibroblasts, which normally do not provide an initiation context. Thus, SATB1 functions as a crucial initiation factor and may act to organize genes for silencing by Xist during the initiation of X inactivation.
Publication Title
SATB1 defines the developmental context for gene silencing by Xist in lymphoma and embryonic cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
Illumina HiSeq 2500
Description
Hematopoietic stem cells (HSCs) are now recognized as a heterogeneous population in self-renewing and differentiation capabilities. However, fundamental mechanisms governing the heterogeneity remain uncertain. We here show that special AT-rich sequence-binding protein 1 (SATB1), a global chromatin organizer, is involved in the mechanisms. Analyzing hematological lineage-restricted SATB1 knock out mice proved that SATB1 is indispensable for both self-renewal and normal differentiation of adult HSCs. Using SATB1/Tomato knock-in mice, we subdivided HSCs according to SATB1 intensity. Culture experiments and RNA-sequencing revealed essential differences between SATB1- and SATB1+ HSCs regarding lineage potential. Overall design: Total RNAs isolated from SATB1- and SATB1+ CD150+ Flt3- LSK cells were applied for RNA-sequencing, and then amount of change of each genetic expression in SATB1+ HSCs compared with SATB1- HSCs were calculated.
Publication Title
Variable SATB1 Levels Regulate Hematopoietic Stem Cell Heterogeneity with Distinct Lineage Fate.
Sample Metadata Fields
Specimen part, Subject
View Samples- Oryza sativa indica group
- 18 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Traditional rice varieties found in India have many desirable characteristics. Amongst them, their differential responses to abiotic and biotic stresses are of great agricultural importance. Drought or osmotic stress is one of the major abiotic stresses afflicting crop plants in India. Indigenous varieties like Dagad deshi have been found to be drought resistant and, thereby, are being studied in great detail by plant breeders and biotechnologists alike. In this study, we have analyzed the transciptomes of two contrasting cultivars, i.e. Dagad deshi (tolerant) and IR20 (susceptible), under control and stress conditions to elucidate the differences in their responses to drought stress using Affymetrix microarray platform.
Publication Title
Reference genes for accurate gene expression analyses across different tissues, developmental stages and genotypes in rice for drought tolerance.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 10 Downloadable Samples
- IlluminaHiSeq2000
Description
we performed RNA sequencing analysis using 10 tissue samples from human prostate and evaluated efficiency and accuracy of eRNA on mRNA-seq data analysis. Overall design: We sequenced mRNAs from the 10 human tissue samples. After that, we identified mRNAs in these samples against known human genes.
Publication Title
eRNA: a graphic user interface-based tool optimized for large data analysis from high-throughput RNA sequencing.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Chronic hepatitis C virus (HCV) infection is now routinely treated with interferon (IFN)-free regimens composed of directly acting antiviral (DAA) agents. Changes in hepatic and peripheral innate and adaptive immune function during DAA therapy associate with achieving a sustained virologic response (SVR). The present study explored the impact of cirrhosis on host endogenous interferon pathways during DAA therapy. mRNA and micro-RNA (miRNA) expression profiling was performed on paired pre- and end-of-treatment (EOT) liver biopsies from subjects treated with a 2 DAA regimen (sofosbuvir/ledipasvir [SOF/LDV]) for 12 weeks (n=4, 3 with cirrhosis) or a 3 DAA regimen (SOF/LDV with GS-9669 or GS-9451) for 6 weeks (n=6, 0 with cirrhosis). Nine of ten subjects achieved SVR, with one relapse in the GS-9669 treatment arm (ISHAK fibrosis 4). Hepatic interferon-stimulated gene expression was down-regulated in the liver of all subjects, with no observable impact of cirrhosis or duration of treatment. Hepatic down-regulation of all type-III IFNs was observed (IFNL1, IFNL2, IFNL3, IFNL4-G), while IFNA2 expression, undetectable in all subjects pre-treatment, was detected in 3 of 9 subjects at EOT (all 3 achieved SVR). Only the subject who relapsed had detectable IFNL4-G expression in EOT liver. No change in IFNB1, IFNG, or IFNA5 expression was observed, and expression of other type-I IFNs (IFNA1, IFNA4, IFNA5, IFNA6, IFNA8, IFNA16, IFNA17) was not detected pre- or post-treatment. While expression of multiple miRNAs changed in liver tissue over the course of treatment, most miRNAs previously associated with HCV replication, innate interferon signaling, and hepatic fibrosis did not change significantly. Conclusions: Changes in the host IFN-response during DAA therapy associate with favorable treatment outcome regardless of composition and duration of therapy or extent of hepatic fibrosis.
Publication Title
Achieving sustained virologic response after interferon-free hepatitis C virus treatment correlates with hepatic interferon gene expression changes independent of cirrhosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Lineage plasticity is a major mechanism driving prostate cancer progression and antiandrogen therapy resistance. Deletions or mutations in phosphatase and tensin homolog (PTEN) and TP53 tumor suppressor genes have been linked to lineage plasticity in prostate cancer. Fusion-driven overexpression of the E-twenty-six transformation specific (ETS)-related gene (ERG), encoding an oncogenic transcription factor, is observed in approximately 50% of all prostate cancers, yet its role in prostate cell lineage determination remains elusive. Here we demonstrate that transgenic expression of prostate cancer-associated ERG blocks Pten and Trp53 mutation-induced decreased expression of Ar and its downstream target genes and loss of luminal epithelial cell identity in the mouse prostate. Integrative analyses of ERG chromatin-immunoprecipitation sequencing (ChIP-seq) and transcriptome data show that ERG suppresses expression of a subset of cell cycle-promoting genes and RB phosphorylation, which in turn causes repression of E2F1-mediated expression of non-epithelial lineage genes. Xenograft studies show that PTEN/TP53 double mutated prostate tumors are responsive to the cyclin-dependent kinase 4 or 6 (CDK4/6) inhibitor palbociclib, but resistant to the AR inhibitor enzalutamide, while ERG/PTEN/TP53 triple-mutated prostate tumors behave completely opposite. Our studies identify ERG and the repressed cell cycle gene signature as intrinsic inhibitors of PTEN/TP53 double mutation-elicited lineage plasticity in prostate cancer. Our findings also suggest that ERG fusion can be utilized as a biomarker to guide the treatment of PTEN/TP53-mutated, RB1-intact prostate cancer with either antiandrogen or anti-CDK4/6 therapies. Overall design: Prostate tissue from mice with 1) prostate specific PTEN deletion, p53 R172H mutation with loss of heterozygosity, or 2) prostate specific PTEN deletion, p53 R172H mutation with loss of heterozygosity and transgenic ERG expression were harvested at 4-5 months. RNA was isolated from tissue and RNA-seq experiments were then performed for both genotype samples in triplicates. Differentially expressed genes were identified by comparing genotype #1 and genotype #2.
Publication Title
<i>TMPRSS2-ERG</i> Controls Luminal Epithelial Lineage and Antiandrogen Sensitivity in <i>PTEN</i> and <i>TP53</i>-Mutated Prostate Cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 31 Downloadable Samples
- Illumina HiSeq 2000
Description
Exosomes, endosome-derived membrane microvesicles, contain a specific set of RNA transcripts that are involved in cell-cell communication and hold a great potential as disease biomarkers. To systemically characterize exosomal RNA profiles, we performed RNA sequencing analysis using three human plasma samples and evaluated efficacies of small RNA library preparation protocols from 3 manufacturers. Overall design: We tested the six samples (A1 and A2, B1 and B2, C1 and C2) using two small RNA library preparation kits: NEBNext Multiplex Small RNA library Prep Set from New England Biolab (NEB) and NEXTflex Small RNA Sequencing Kit from Bioo Scientific (BS). We also tested Illumina’s TrueSeq Small RNA Sample Preparation Kit (ILMN) in sample A1 and A2. Together, we tested these plasma samples by sequencing 14 indexed libraries. This study allowed direct comparison of current small RNA library preparation protocols and identified the most suitable strategy for future exosomal RNA sequencing analysis.
Publication Title
Characterization of human plasma-derived exosomal RNAs by deep sequencing.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Mutations in the parkin gene, which encodes a ubiquitin ligase, are a major genetic cause of parkinsonism. Interestingly, parkin also plays a role in cancer as a putative tumor suppressor, and the gene is frequently targeted by deletion and inactivation in human malignant tumors. Here, we investigated a potential tumor suppressor role for parkin in gliomas. We found that parkin expression was dramatically reduced in glioma cells. Restoration of parkin expression promoted G1 phase cell cycle arrest and mitigated the proliferation rate of glioma cells in vitro and in vivo. Notably, parkin-expressing glioma cells showed a reduction in levels of cyclin D1, but not cyclin E, and a selective downregulation of Akt serine-473 phosphorylation and VEGF receptor levels. In accordance, cells derived from a parkin null mouse model exhibited increased levels of cyclin D1, VEGF receptor and Akt phosphorylation and divided significantly faster when compared with wild type cells, with suppressionof these changes following parkin re-introduction. Clinically, analysis of parkin pathway activation was predictive for the survival outcome of glioma patients. Taken together, our study provides mechanistic insight into the tumor suppressor function of parkin in brain tumors, and suggests that measurement of parkin pathway activation may be used clinically as a prognostic tool in brain tumor patients.
Publication Title
Parkin pathway activation mitigates glioma cell proliferation and predicts patient survival.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Aberrant expression of immune checkpoint protein programmed death ligand-1 (PD-L1) promotes immune tolerance in cancer. RB is a tumor suppressor known to regulate the cell cycle, DNA damage response, and differentiation. Here, we demonstrate transient knockdown or homozygous deletion of RB markedly induces PD-L1 mRNA expression. RB binds to NF?B protein p65 and serine-249/threonine-252 (S249/T252) phosphorylation of RB is important for its interaction with p65 and suppression of PD-L1 expression. RNA-seq analysis identifies a subset of NF?B pathway genes including PD-L1 are selectively upregulated by RB knockdown. S249/T252-phosphorylated RB inversely correlates with PD-L1 expression in patient samples. Expression of a RB-derived S249/T252 phospho-mimicking peptide blocks radiation-induced PD-L1 expression and increases the anti-cancer efficacy of radiation in mice. Our findings reveal a previously unappreciated tumor suppressor function of hyperphosphorylated RB in inhibition of NF?B activity and PD-L1 expression, suggesting this regulatory module can be exploited to overcome cancer immune evasion. Overall design: Examination of RNA expression in PC-3 cells knocked down endogenous RB or treated cells with the CDK4/6 inhibitor palbociclib
Publication Title
Phosphorylated RB Promotes Cancer Immunity by Inhibiting NF-κB Activation and PD-L1 Expression.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples