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Platform
GSE68504
Homo sapiens
12 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
FUS Regulates Activity of MicroRNA-Mediated Gene Silencing.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Individuals with the ALS-linked (amyotrophic lateral sclerosis) truncation mutation (R495X) in FUS (fused in sarcoma) are known to have a more aggressive form of the disease than those with point mutations. The underlying cause for this difference is unclear. We report that FUS is a component of miRISC (miRNA-induced silencing complex) and that overexpression of its truncation mutant R495X negatively impacts miRNA mediated RNA silencing.
Publication Title
FUS Regulates Activity of MicroRNA-Mediated Gene Silencing.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
T cells contribute to host-tumor interactions in patients with monoclonal gammopathies. Expansions of CD8+CD57+TCRV+ restricted cytotoxic T cell (CTL) clones are found in 48% of patients with multiple myeloma and confer a favorable prognosis. We now report the presence of CTL clones with varying TCRV repertoire in 70% of patients with Waldenstroms Macroglobulinaemia (WM) (n=20). Previous nucleoside analogue (NA) therapy, associated with an increased incidence of transformation to aggressive lymphoma, significantly influenced the presence of TCRV expansions (X2=11.6; P<0.001) as 83% of patients without (n=6) and only 7% with TCRV expansions (n=14) had received NA. Clonality of CD3+CD8+CD57+TCRV+ restricted CTLs were confirmed by TCRV CDR3 size analysis and direct sequencing. To characterize CTL clones, samples of CD3+CD8+CD57+TCRV+ cells were profiled using DNA microarrays and the results were validated on both gene and protein level. By gene set enrichment analysis, CTL clones not only expressed genes (GZMB, PRF1, FGFBP2) from cytotoxic pathways but also genes which suppress apoptosis, inhibit proliferation, arrest cell cycle G1/S transition and activate T cells (RAS, CSK and TOB pathways). Proliferation tracking confirmed their anergic state. Our studies demonstrate the incidence, NA sensitivity and anergic nature of clonal T cells in a B cell tumor.
Publication Title
Clonal expansions of cytotoxic T cells exist in the blood of patients with Waldenstrom macroglobulinemia but exhibit anergic properties and are eliminated by nucleoside analogue therapy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Tumor metastasis and lack of NKG2D ligand (NKG2DL) expression are associated with poor prognosis in patients with colon cancer. Here we found that spironolactone (SPIR), an FDA-approved diuretic drug with a long-term safety profile, can upregulate NKG2DL expression in multiple colon cancer cell lines by activating the ATM-Chk2-mediated checkpoint pathway, which in turn enhances tumor elimination by natural killer cells. SPIR can also upregulate the expression of metastasis-suppressor genes TIMP2 and TIMP3, thereby reducing tumor cell invasiveness. Although SPIR is an aldosterone antagonist, its anti-tumor effects are independent of the mineralocorticoid receptor pathway. Instead, by screening the human nuclear hormone receptor siRNA library, we identify retinoid X receptor gamma (RXR gamma) as being indispensable for the anti-tumor functions of SPIR. Collectively, our results strongly support the use of SPIR or other RXR gamma-agonists with minimal side effects for colon cancer prevention and therapy.
Publication Title
Modulation of NKG2D ligand expression and metastasis in tumors by spironolactone via RXRγ activation.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have employed whole genome microarray expression profiling to identify genes differentially expressed in cord blood purified neutrophils after a short-term exposure to peptidoglycan (PGN).
Publication Title
Expression profile of cord blood neutrophils and dysregulation of HSPA1A and OLR1 upon challenge by bacterial peptidoglycan.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Thymocyte selection-associated high mobility group box protein family member 2 (TOX2) is a transcription factor belonging to the TOX family that shares a highly conserved high mobility group DNA binding domain with the other TOX members. While TOX1 has been shown to be an essential regulator of T-cell and natural killer (NK) cell differentiation in mice, little is known about the roles of the other TOX family members in lymphocyte development, particularly in humans. In this study, we found that TOX2 was preferentially expressed in mature human NK cells and was upregulated during in vitro differentiation of NK cells from human umbilical cord blood (UCB)derived CD34+ cells. Gene silencing of TOX2 intrinsically hindered the transition between early developmental stages of NK cells, while overexpression of TOX2 enhanced the development of mature NK cells from UCB CD34+ cells. We subsequently found that TOX2 was independent of ETS-1 but could directly upregulate the transcription of TBX21 (encoding T-BET). Overexpression of T-BET rescued the TOX2 knockdown phenotypes. Given the essential function of T-BET in NK cell differentiation, TOX2 therefore plays a crucial role in controlling normal NK cell development by acting upstream of TBX21 transcriptional regulation.
Publication Title
TOX2 regulates human natural killer cell development by controlling T-BET expression.
Sample Metadata Fields
Specimen part, Subject
View Samples- Danio rerio
- 6 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Eye development and photoreceptor maintenance requires the retinal pigment epithelium (RPE), a thin layer of cells that underlies the neural retina. Despite its importance, RPE development has not been studied by a genomic approach. A microarray expression profiling methodology was established in this study for studying RPE development. The intact retina with RPE attached was dissected from developing embryos, and differentially expressed genes in RPE were inferred by comparing the dissected tissues with retinas without RPE using microarray and statistical analyses. We found 8810 probesets to be significantly expressed in RPE at 52 hours post-fertilization (hpf), of which 1443 might have biologically meaningful expression levels. Further, 78 and 988 probesets were found to be significantly over- or under-expressed in RPE respectively compared to retina. Also, 79.2% (38/48) of the known over-expressed probesets have been independently validated as RPE-related transcripts. The results strongly suggest that this methodology can obtain in vivo RPE specific gene expression from the zebrafish embryos and identify novel RPE markers.
Publication Title
Gene expression profiling of zebrafish embryonic retinal pigment epithelium in vivo.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 24 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Retinal cells are specified in a zebrafish recessive mutant called young (yng) but they fail to terminally differentiate; i.e. extend neurites and make synaptic contacts. A point mutation in a brahma-related gene 1 (brg1) is responsible for this phenotype. In this microarray study, a three-factor factorial design was utilized to investigate the effects of 1) mutation, 2) change in time (36 vs. 52hpf), and 3) change in tissue (retina vs. whole embryos), and their interactions on gene expression. Significant probesets were inferred by using both specific contrasts of the fitted Analysis of Variance (ANOVA) models and a corresponding 2-fold expression cutoff. The probesets were grouped into three broad categories: 1) Brg1-regulated retinal differentiation genes (731 probsets), 2) Retinal specific genes but independent of Brg1 regulation (3038 probesets) and 3) Genes regulated by Brg1 but outside the retina (107 probesets). Four gene groups/pathways including neurite outgrowth regulators, Delta-Notch signalling molecules, Irx family members and specific cell cycle regulators were identified in the first group, and their relevance for retinal differentiation functionally validated. This study demonstrates that an approach such as ours can identify relevant genes and pathways involved in retinal development as well as the development of other tissues at the same time.
Publication Title
Factorial microarray analysis of zebrafish retinal development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 75 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
We used microarrays to compare gene expression profiles between mouse mammary tumors initiated by Myc to those that have escaped Myc oncogene dependence.
Publication Title
Heterogeneity in MYC-induced mammary tumors contributes to escape from oncogene dependence.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To examine the differences between bone marrow (BM) and peripheral blood (PB) myeloblasts in acute myeloid leukaemia (AML), we compared CD34+ myeloblasts of paired BM and peripheral blood (PB) samples from AML patients using microarray.
Publication Title
A comparative study of bone marrow and peripheral blood CD34+ myeloblasts in acute myeloid leukaemia.
Sample Metadata Fields
No sample metadata fields
View Samples