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GSE58457
Homo sapiens
11 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Human induced pluripotent stem cells (iPS cells) resemble embryonic stem cells and can differentiate into cell derivatives of all three germ layers. However, frequently the differentiation efficiency of iPS cells into some lineages is rather poor. Here, we found that fusion of iPS cells with human hematopoietic stem cells (HSC) enhances iPS cell differentiation. Such iPS hybrids showed a prominent differentiation bias towards hematopoietic lineages but also towards other mesendodermal lineages. Additionally, during differentiation of iPS hybrids expression of early mesendodermal markers - Brachyury (T), MIX1 Homeobox-Like Protein 1 (MIXL1) and Goosecoid (GSC) - appeared with faster kinetics than in parental iPS cells. Following iPS hybrid differentiation there was a prominent induction of NODAL and inhibition of NODAL signaling blunted mesendodermal differentiation. This indicates that NODAL signaling is critically involved in mesendodermal bias of iPS hybrid differentiation. In summary, we demonstrate that iPS cell fusion with HSC prominently enhances iPS differentiation.
Publication Title
Cell fusion enhances mesendodermal differentiation of human induced pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Conventional anti-cancer drug screening is typically performed in the absence of accessory cells (e.g. stromal cells) of the tumor microenvironment, which can profoundly alter anti-tumor drug activity. To address this major limitation, we have developed assays (e.g. the tumor cell-specific in vitro bioluminescence imaging (CS-BLI) assay) to selectively quantify tumor cell viability, in presence vs. absence of non-malignant stromal cells or drug treatment. These assays have allowed us to identify that neoplastic cells from diverse malignancies exhibit stroma-induced resistance to different anti-tumor agents. In this analysis, we evaluated the molecular changes triggered in myeloma cells by their in vitro interaction with stromal cells. The transcriptional profile of 3 human multiple myeloma (MM) cell lines (MM.1S, MM.1R, INA-6) co-cultured with stromal cells vs. when cultured alone was characterized by oligonucleotide microarray analysis, using the human U133 plus 2.0 Affymetrix GeneChip.
Publication Title
Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anticancer drug activity.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Estrogen signaling pathway is critical for breast cancer development and has remained the major adjuvant therapeutic target for this disease. Tamoxifen has been used in clinic for many years to treat ER-positive breast cancer. However a great many (30%) suffer relapse due to drug resistance. In this study, the bromodomain inhibitor JQ1 was found to down-regulate ERalpha gene expression and have anti-tumor effect in cultured tamoxifen-resisant breast cancer cells.
Publication Title
An epigenomic approach to therapy for tamoxifen-resistant breast cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
- (ffymetrixhumanexon1.0starray[cdf:huex10stv2,corer3,a20071112,ep)
Description
The androgen receptor (AR) is a key driver of prostate cancer (PC), even in the state of castration-resistant PC (CRPC), and frequently even after treatment with second-line hormonal therapies such as abiraterone and enzalutamide. The persistence of AR activity via both ligand-dependent and ligand-independent (including constitutively active AR splice variants) mechanisms highlights the unmet need for alternative approaches to block AR signaling in CRPC. We investigated the transcription factor GATA2 as a regulator of AR signaling and a novel therapeutic target in PC. We demonstrate that GATA2 directly promotes AR expression (both full-length and splice variant), resulting in a strong positive correlation between GATA2 and AR expression in PC (cell lines and patient specimens). Conversely, GATA2 expression is repressed by androgen and AR, suggesting a negative feedback regulatory loop that, upon androgen deprivation, derepresses GATA2 to contribute to AR overexpression in CRPC. Simultaneously, GATA2 is necessary for optimal transcriptional activity of AR (both full-length and splice variant). GATA2 co-localizes with AR and FOXA1 on chromatin to enhance recruitment of steroid receptor coactivators (SRCs) and formation of the transcriptional holocomplex. In agreement with these important functions, high GATA2 expression and transcriptional activity predicted for worse clinical outcome in PC patients. A GATA2 small molecule inhibitor suppressed the expression and transcriptional function of AR (both full-length and splice variant) and exerted potent anticancer activity against PC cell lines. We propose pharmacological inhibition of GATA2 as a first-in-field approach to target AR expression and function and improve outcomes in CRPC.
Publication Title
GATA2 facilitates steroid receptor coactivator recruitment to the androgen receptor complex.
Sample Metadata Fields
Cell line
View Samples- Drosophila melanogaster
- 13 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We previously found a short sleeper mutant, fmn, and identified its mutation in the dopamine transporter gene. In an attempt to discover additional sleep related genes in Drosophila, we carried out a microarray analysis comparing mRNA expression in heads of fmn and control flies and found differentially expressed genes.
Publication Title
The NMDA Receptor Promotes Sleep in the Fruit Fly, Drosophila melanogaster.
Sample Metadata Fields
Sex, Specimen part
View Samples- Arabidopsis thaliana
- 20 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The Arabidopsis thaliana NAC domain transcription factor, VASCULAR-RELATED NAC-DOMAIN7 (VND7), acts as a key regulator of xylem vessel differentiation. In order to identify direct target genes of VND7, we performed global transcriptome analysis using Arabidopsis transgenic lines in which VND7 activity could be induced post-translationally. This analysis identified 63 putative direct target genes of VND7, which encode a broad range of proteins, such as transcription factors, IRREGULAR XYLEM proteins and proteolytic enzymes, known to be closely associated with xylem vessel formation. Recombinant VND7 protein binds to several promoter sequences present in candidate direct target genes: specifically, in the promoter of XYLEM CYSTEINE PEPTIDASE1, two distinct regions were demonstrated to be responsible for VND7 binding. We also found that expression of VND7 restores secondary cell wall formation in the fiber cells of inflorescence stems of nst1nst3 double mutants, as well as expression of NAC SECONDARY WALL THICKENING PROMOTING FACTOR3 (NST3, however, the vessel-type secondary wall deposition was observed only as a result of VND7 expression. These findings indicated that VND7 upregulates, directly and/or indirectly, many genes involved in a wide range of processes in xylem vessel differentiation, and that its target genes are partially different from those of NSTs.
Publication Title
VASCULAR-RELATED NAC-DOMAIN7 directly regulates the expression of a broad range of genes for xylem vessel formation.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hsp90 is critical for regulation of the phenotype and functional activity of human T lymphocytes and natural killer (NK) cells.
Publication Title
Heat shock protein 90 is critical for regulation of phenotype and functional activity of human T lymphocytes and NK cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
In this study, we sought to establish the usefulness of LCM on cDNA microarray analysis. We reported that LCM samples improved the sensitivity of detection of differentially expressed genes over conventional bulk tissue analysis. We also provided the new information of chemokine and its receptor interaction within psoriatic lesional skin.
Publication Title
Combined use of laser capture microdissection and cDNA microarray analysis identifies locally expressed disease-related genes in focal regions of psoriasis vulgaris skin lesions.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 36 Downloadable Samples
Illumina HiSeq 2000
Description
Neuropathic pain is a complex chronic condition, characterized by a wide range of sensory, cognitive, and affective symptoms. Indeed, a large percentage of neuropathic pain patients are also afflicted with depression and anxiety disorders -- a pattern that is reliably replicated in animal models. Mounting evidence from clinical and preclinical studies indicates that chronic pain corresponds with adaptations in several brain networks involved in mood, motivation, and reward. Chronic stress is also a major determinant for depression. However, whether chronic pain and chronic stress affect similar mechanisms, and whether chronic pain can affect gene expression patterns known to be involved in depression, remains poorly understood. We employed the spared nerve injury model (SNI) of neuropathic pain in adult C57BL\6 mice and performed next-generation RNA-sequencing in order to monitor changes in gene expression in three brain regions known to be implicated in the pathophysiology of depression and in the modulation of pain: the nucleus accumbens (NAc), the medial prefrontal cortex (mPFC), and the periaqueductal grey (PAG). We observed mostly unique transcriptome profiles across the three brain regions but found common intracellular signal transduction pathways and biological functions were affected. A large amount of genes showing SNI-induced altered expression have been implicated in depression, anxiety, or chronic pain. In addition, we identified genes that are similarly regulated in a murine model of depression: chronic unpredictable stress. Our study provides the first unbiased characterization of neuropathic pain-induced long-term gene expression changes in three distinct brain regions, and presents evidence that neuropathic pain affects the expression of several genes that are also regulated by chronic stress. Overall design: RNA-seq samples were generated from 3 brain regions (nucleus accumbens, medial prefrontal cortex, and periaqueductal grey) of adult male mice, 2.5 months after sham or spared nerve injury to the sciatic nerve.
Publication Title
Neuropathic pain promotes adaptive changes in gene expression in brain networks involved in stress and depression.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We hypothesize that gene expression in the aging lungs of these two strains of mice are divergent thus contributing to the disparity in the phenotypes. More specifically, (1) Aging DBA/2J mice compared to aging C57BL/6 mice are known to be accelerated in their lung physiology and morphometry; (2) C57BL/6J are known to have longer natural longevity than DBA/2J mice. In order to test these hypotheses at the gene expression level, we utilized microarray analysis to examine transcriptional differences between aging lungs of both strains of mice.
Publication Title
Global expression profiles from C57BL/6J and DBA/2J mouse lungs to determine aging-related genes.
Sample Metadata Fields
No sample metadata fields
View Samples