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GSE18088
Homo sapiens
51 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background Published multi-gene classifiers suggested outcome prediction for patients with stage UICC II colon cancer based on different gene expression signatures. However, there is currently no translation of these classifiers for application in routine diagnostic. Therefore, we aimed at validating own and published gene expression signatures employing methods which enable RNA and protein detection in routine diagnostic specimens. Results Immunohistochemistry was applied to 68 stage UICC II colon cancers to determine the protein expression of five selected previously published classifier genes (CDH17, LAT, CA2, EMR3, and TNFRSF11A). Correlation of protein expression data with clinical outcome within a 5-year post-surgery course failed to separate patients with a disease-free follow-up [Group DF] and relapse [Group R]). In addition, RNA from macrodissected tumor samples from 53 of these 68 patients was profiled on Affymetrix GeneChips (HG-U133 Plus 2.0). Prognostic signatures were generated by Nearest Shrunken Centroids with cross-validation. Although gene expression profiling allowed the identification of differentially expressed genes between the groups DF and R, a stable classification and prognosis signature was not discernable in our data. Furthermore, the application of previously published gene signatures consisting of 22 and 19 genes, respectively, to our gene expression data set using global tests and leave-one-out cross-validation was unable to predict clinical outcome (prediction rate 75.5% and 64.2%; n.s.). T-stage was the only independent prognostic factor for relapse in multivariate analysis with established clinical and pathological parameters including microsatellite status. Conclusions Our protein and gene expression analyses currently do not support application of molecular classifiers for prediction of clinical outcome in routine diagnostic as a basis for patient-orientated therapy in stage UICC II colon cancer. Further studies are needed to develop prognosis signatures applicable in patient care.
Publication Title
Molecular profiles and clinical outcome of stage UICC II colon cancer patients.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cutaneous T-cell lymphomas form a heterogeneous group of non-Hodgkin lymphomas characterized by only poor prognosis in advanced stage. Despite significant progress made in the identification of novel genes and pathways involved in the pathogenesis of cutaneous lymphoma, the therapeutic value of these findings has still to be proven. Here, we demonstrate by gene expression arrays that aurora kinase A is one of highly overexpressed genes of the serine/threonine kinase in CTCL. The finding was confirmed by qualitative RT-PCR, Western blotting and immunohistochemistry in CTCL cell lines and primary patient samples. Moreover, treatment with a specific aurora kinase A inhibitor blocks cell proliferation by inducing cell cycle arrest in G2 phase as well as apoptosis in CTCL cell lines. These new data provide a promising rationale for using aurora kinase A inhibition as a therapeutic modality of CTCL.
Publication Title
Aurora Kinase A Is Upregulated in Cutaneous T-Cell Lymphoma and Represents a Potential Therapeutic Target.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
Illumina HiSeq 2500
Description
A key limitation in single cell genomics is generating a high-quality single cell suspension that contains rare or difficult to dissociate cell types and is free of RNA degradation or transcriptional stress responses. Samples with unpredictable availability or that must be collected at several timepoints present additional challenges. Using adult mouse kidney, we compared single-cell RNA sequencing (scRNA-seq) data generated using DropSeq with snRNA-seq data generated from nuclei using sNuc-DropSeq, DroNc-seq and 10X Chromium. We validated snRNA-seq on fibrotic kidney from day 14 unilateral ureteral obstruction (UUO). Overall design: Dropseq, sNucDropseq, DroNcSeq and 10X Chromium were used to profile mouse healthy and fibrotic kidneys
Publication Title
Advantages of Single-Nucleus over Single-Cell RNA Sequencing of Adult Kidney: Rare Cell Types and Novel Cell States Revealed in Fibrosis.
Sample Metadata Fields
Subject
View Samples- Mus musculus, Homo sapiens
- 19 Downloadable Samples
- Affymetrix HT MG-430 PM Array Plate (htmg430pm), Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Macrophages are amongst the major targets of glucocorticoids (GC) as therapeutic anti-inflammatory agents. Here we show that GC treatment of mouse and human macrophages initiates a cascade of induced gene expression including many anti-inflammatory genes. Inducible binding of the glucocorticoid receptor (GR) was detected at candidate enhancers in the vicinity of induced genes in both species and this was strongly associated with canonical GR binding motifs. However, the sets of inducible genes, the candidate enhancers, and the GR motifs within them, were highly-divergent between the two species.
Publication Title
Enhancer Turnover Is Associated with a Divergent Transcriptional Response to Glucocorticoid in Mouse and Human Macrophages.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 19 Downloadable Samples
Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm), Affymetrix HT MG-430 PM Array Plate (htmg430pm)
Description
Macrophages are amongst the major targets of glucocorticoids (GC) as therapeutic anti-inflammatory agents. Here we show that GC treatment of mouse and human macrophages initiates a cascade of induced gene expression including many anti-inflammatory genes. Inducible binding of the glucocorticoid receptor (GR) was detected at candidate enhancers in the vicinity of induced genes in both species and this was strongly associated with canonical GR binding motifs. However, the sets of inducible genes, the candidate enhancers, and the GR motifs within them, were highly-divergent between the two species.. The data cast further doubt upon the predictive value of mouse models of inflammatory disease.
Publication Title
Enhancer Turnover Is Associated with a Divergent Transcriptional Response to Glucocorticoid in Mouse and Human Macrophages.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Bos taurus
- 19 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Thecal tissue forms a layer around the follicle just prior to antral stage and grows with the follicle (containing an oocyte) as it matures. The innermost component (theca interna) supplies hormones and other factors necessary to the growth and development of the granulosa and oocyte. Most follicles regress and die (become atretic) at the antral stage, and this process as well as development of the follicle are undoubtedly influenced by the theca.
Publication Title
Transcriptome profiling of the theca interna in transition from small to large antral ovarian follicles.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
BACKGROUND: Hox genes are implicated in hematopoietic stem cell (HSC) regulation as well as in leukemia development through translocation with the nucleoporin gene NUP98. Interestingly, an engineered NUP98-HOXA10 (NA10) fusion can induce a several hundred-fold expansion of HSCs in vitro and NA10 and the AML-associated fusion gene NUP98-HOXD13 (ND13) have a virtually indistinguishable ability to transform myeloid progenitor cells in vitro and to induce leukemia in collaboration with MEIS1 in vivo. METHODOLOGY/PRINCIPAL FINDINGS: These findings provided a potentially powerful approach to identify key pathways mediating Hox-induced expansion and transformation of HSCs by identifying gene expression changes commonly induced by ND13 and NA10 but not by a NUP98-Hox fusion with a non-DNA binding homedomain mutation (N51S). The gene expression repertoire of purified murine bone marrow Sca-1+Lin- cells transduced with retroviral vectors encoding for these genes was established using the Affymetrix GeneChip MOE430A. Approximately seventy genes were differentially expressed in ND13 and NA10 cells that were significantly changed by both compared to the ND13(N51S) mutant. Intriguingly, several of these potential Hox target genes have been implicated in HSC expansion and self-renewal, including the tyrosine kinase receptor Flt3, the prion protein, Prnp, hepatic leukemia factor, Hlf and Jagged-2, Jag2. CONCLUSIONS: In conclusion this study has identified several novel Hox downstream target genes and provides important new leads to key regulators of the expansion and transformation of hematopoietic stem cells by Hox.
Publication Title
Candidate genes for expansion and transformation of hematopoietic stem cells by NUP98-HOX fusion genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Geminin is a small nucleoprotein that neuralizes ectoderm in the Xenopus embryo. Geminin promotes neural fate acquisition of mouse embryonic stem cells: Geminin knockdown during neural fate acquisition decreased expression of neural precursor cell markers (Pax6, Sox1), while increasing expression of Pitx2, Lefty1 and Cited2, genes involved in formation of the mouse node. Here we differentiated mouse embryonic stem cells into embryoid bodies to study Geminin's ability to repress primitive streak mesendoderm fate acquisition. We used microarrays to define the sets of genes that are regulated by Geminin during cell fate acquisition in embryoid bodies, using Dox-inducible Geminin knockdown or overexpression mouse embryonic stem cell lines.
Publication Title
Geminin restrains mesendodermal fate acquisition of embryonic stem cells and is associated with antagonism of Wnt signaling and enhanced polycomb-mediated repression.
Sample Metadata Fields
Specimen part
View Samples- Xenopus laevis
- 12 Downloadable Samples
- Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
Geminin cooperates with Polycomb to restrain multi-lineage commitment in the early embryo: Transient maintenance of a pluripotent embryonic cell population followed by the onset of multi-lineage commitment is a fundamental aspect of development. However, molecular regulation of this transition is not well characterized in vivo. Here we demonstrate that the nuclear protein Geminin is required to restrain commitment and spatially restrict mesoderm, endoderm, and non-neural ectoderm to their proper locations in the Xenopus embryo. We used microarray analyses to demonstrate that Geminin overexpression represses many genes associated with cell commitment and differentiation, while elevating expression levels of genes that maintain pluripotent early and immature neurectodermal cell states. We characterized Geminins relationship to cell signaling and found that Geminin broadly represses Activin-, FGF-, and BMP-mediated cell commitment. Conversely, Geminin knockdown enhances commitment responses to growth factor signaling and causes ectopic mesodermal, endodermal, and epidermal fate commitment in the embryo. We also characterized Geminins functional relationship with transcription factors that had similar activities and found that Geminin represses commitment independent of Oct4 ortholog (Oct25/60) activities, but depends upon intact Polycomb repressor function. Consistent with this, chromatin immunoprecipitation assays directed at mesodermal genes demonstrate that Geminin promotes Polycomb binding and Polycomb-mediated repressive histone modifications, while inhibiting modifications associated with gene activation. This work defines Geminin as an essential regulator of the embryonic transition from pluripotency through early multi-lineage commitment, and demonstrates that functional cooperativity between Geminin and Polycomb contributes to this process.
Publication Title
Geminin cooperates with Polycomb to restrain multi-lineage commitment in the early embryo.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens, Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Dynamic interaction between prostate cancer and the bone microenvironment is a major contributor to metastasis of prostate cancer to bone. In this study we utilized an in-vitro co-culture model of PC3 prostate cancer cells and osteoblasts followed by microarray based gene expression profiling to identify previously unrecognized prostate cancer-bone microenvironment interactions. Factors secreted by PC3 cells resulted in the up-regulation of many genes in osteoblasts associated with bone metabolism and cancer metastasis, including Mmp13, Il-6 and Tgfb2, and down-regulation of Wnt inhibitor Sost. To determine whether altered Sost expression in the bone microenvironment has an effect on prostate cancer metastasis, we co-cultured PC3 cells with Sost knockout (SostKO) osteoblasts and wildtype (WT) osteoblasts and identified several genes differentially regulated between PC3-SostKO osteoblast co-cultures and PC3-WT osteoblast co-cultures. Co-culturing PC3 cells with WT osteoblasts up-regulated cancer-associated long noncoding RNA (lncRNA) MALAT1 in PC3 cells. MALAT1 expression was further enhanced when PC3 cells were co-cultured with SostKO osteoblasts and treatment with recombinant Sost down-regulated MALAT1 expression in these cells. Our results suggest that reduced Sost expression in the tumor microenvironment may promote bone metastasis by up-regulating MALAT1 in prostate cancer.
Publication Title
Cancer-Osteoblast Interaction Reduces Sost Expression in Osteoblasts and Up-Regulates lncRNA MALAT1 in Prostate Cancer.
Sample Metadata Fields
Cell line
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