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SRP042124
Mus musculus
4 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Analysis of class switch recombination, maturation or differenciation of B cells at gene expression levels. The hypothesis tested in the present study was that TLR signaling in B cells plays an pivotal role for class switch, maturation and differenciation. Overall design: Total RNA obtained from cultured splenic B cells. Gene expression compared between control and cKO B cells.
Publication Title
Control of Toll-like receptor-mediated T cell-independent type 1 antibody responses by the inducible nuclear protein IκB-ζ.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
DNA methylation profiling of embryonic stem cell differentiation into the three germ layers.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Embryogenesis is tightly regulated by multiple levels of epigenetic systems such as DNA methylation, histone modification, and chromatin remodeling. DNA methylation patterns are erased in primordial germ cells and in the interval immediately following fertilization. Subsequent reprogramming occurs by de novo methylation and demethylation. Variance of DNA methylation patterns between different cell types is not well understood. Here, using methylated DNA immunoprecipitation and tiling array technology, we have comprehensively analysed DNA methylation patterns at proximal promoter regions in mouse embryonic stem (ES) cells, ES cell-derived early germ layers (ectoderm, endoderm and mesoderm) and four adult tissues (brain, liver, skeletal muscle and sperm). Most of the methylated regions in the three germ layers and in the three adult somatic tissues are shared in common. This commonly methylated gene set is enriched in germ cell associated genes that are generally transcriptionally inactive in somatic cells. We also compared DNA methylation patterns with global mapping of histone H3 lysine 4/27 trimethylation, and found that gain of DNA methylation correlates with loss of histone H3 lysine 4 trimethylation. Taken together, our findings indicate that differentiation from ES cells to the three germ layers is accompanied by an increase in the number of commonly methylated DNA regions and that these tissue-specific alterations are present for only a small number of genes. Our findings indicate that DNA methylation at the proximal promoter regions of commonly methylated genes act as an irreversible mark which fixes somatic lineage by repressing transcription of germ cell specific genes.
Publication Title
DNA methylation profiling of embryonic stem cell differentiation into the three germ layers.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Aberrant DNA methylation, one of the major epigenetic alterations in cancer, has been reported to accumulate in a subset of colorectal cancer (CRC), so-called CpG island methylator phenotype (CIMP), which was known to correlate with microsatellite instability (MSI)-high CRC. To select new methylation markers genome-widely and epigenotype CRC by DNA methylation comprehensively, we performed methylated DNA immunoprecipitation-on-chip analysis using MSI-high CRC cell line HCT116 and microsatellite-stable SW480, and re-expression array analysis by 5-aza-2-deoxycytidine/Trichostatin A. Methylation levels of 44 new markers selected and 16 previously reported markers were analyzed quantitatively in 149 clinical CRC samples using MALDI-TOF mass spectrometry. By unsupervised two-way hierarchical clustering, CRC was clustered into high-, intermediate-, and low-methylation epigenotypes. Methylation markers were clustered into two groups: Group-1 showing methylation in high-methylation epigenotype and including all the 11 CIMP-related markers except NEUROG1, and Group-2 showing methylation in high- and intermediate-methylation epigenotypes. Marker panel deciding methylation epigenotypes with the highest accuracy was developed: 1st-Panel consisting of Group-1 genes (CACNA1G, LOX, SLC30A10) to extract high-methylation epigenotype, and 2nd-Panel consisting of Group-2 genes (ELMO1, FBN2, THBD, HAND1) and SLC30A10 again to divide the remains into intermediate- and low-methylation epigenotypes. High-methylation epigenotype correlated significantly with BRAF mutation, MSI, proximal tumor location, and mucinous component, in concordance with reported CIMP. Intermediate- and low-methylation epigenotypes significantly correlated with KRAS-mutation(+) and KRAS-mutation(-), respectively. KRAS-mutation(+) intermediate-methylation epigenotype showed worse prognosis than KRAS-mutation(-) low-methylation epigenotype (p=0.030). These three epigenotypes with different genetic characteristics suggested different molecular CRC genesis, and the markers might be useful to predict prognosis.
Publication Title
Three DNA methylation epigenotypes in human colorectal cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 66 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
PRC2 overexpression and PRC2-target gene repression relating to poorer prognosis in small cell lung cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 66 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Small cell lung cancer (SCLC) is a subtype of lung cancer with poor prognosis due to early dissemination and rapid growth. We here analyze gene expression profile of 23 clinical SCLC samples. EZH2 was found to be highly expressed in SCLC samples compared to 42 normal tissues including the normal lung, and other PRC2 members, SUZ12 and EED, were also highly expressed in SCLC. To obtain target genes of PRC2 in SCLC, H3K27me3 mark was mapped in three SCLC cell lines, Lu130, H209 and DMS53, and compared to normal small airway epithelial cells (SAEC). Whereas H3K27me3(+) genes in SAEC were significantly overlapped with PRC-target genes in ES cells (P=1.7x10-31), genes with H3K27me3 in SCLC cell lines but not in SAEC were not significantly overlapped with PRC-target genes in ES cells (P=0.64). These genes with H3K27me3 specifically in SCLC cell lines but not in SAEC showed decreased expression, not only in SCLC cell lines but also in clinical SCLCs, and showed enrichment of GO-terms such as plasma membrane (P=8.1x10-21) and cell adhesion (P=1.7x10-8). Introduction of JUB, a gene showing specific H3K27me3 modification and the strongest repression in the three SCLC cell lines, resulted in repression of cellular growth in DMS53. In clinical SCLC cases, lower JUB level correlated to shorter survival (P=0.002), or a set of PRC target genes (JUB, EPHB4) and marker genes of classic type SCLC (GRP, ASCL1) correlated to shorter survival (P=0.0001) and classified SCLC into two groups with distinct prognosis. Growth of SCLC cell lines was repressed when treated with 3-Deazaneplanocin A, an inhibitor against PRC2. It is suggested that high expression of PRC2 in SCLC contributed to repression of genes including non-PRC-target genes in ES cells, and that the gene repression may play a role in genesis of SCLC.
Publication Title
PRC2 overexpression and PRC2-target gene repression relating to poorer prognosis in small cell lung cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To elucidate whether or not a subtype of adenocarcinoma with neuroendocrine nature has poor prognosis, we performed gene expression profiling of an achaete-scute complex homolog 1 (ASCL1) siRNA experiment.
Publication Title
ASCL1-coexpression profiling but not single gene expression profiling defines lung adenocarcinomas of neuroendocrine nature with poor prognosis.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
Background. Androgen receptor splice variant-7 (AR-V7) is a truncated form of the androgen receptor protein which lacks the ligand-binding domain, the target of enzalutamide and abiraterone, but remains constitutively active as a transcription factor. We hypothesized that detection of AR-V7 in circulating tumor cells (CTCs) from men with advanced prostate cancer would be associated with resistance to enzalutamide and abiraterone. Methods. We used quantitative reverse-transcription polymerase-chain-reaction (qRT-PCR) to interrogate CTCs for the presence or absence of AR-V7 from prospectively enrolled patients with metastatic castration-resistant prostate cancer initiating treatment with either enzalutamide or abiraterone. We examined associations between AR-V7 status and PSA response rates, PSA-progression-free-survival (PSA-PFS), clinical/radiographic-progression-free-survival (PFS), and overall survival (OS). Multivariable Cox regression analyses were performed to determine the independent effect of AR-V7 status on clinical outcomes. Results. Thirty-one enzalutamide-treated patients and thirty-one abiraterone-treated patients were enrolled, of which 38.7% and 19.4% had detectable AR-V7 from CTCs, respectively. Among men receiving enzalutamide, AR-V7–positive patients had inferior PSA response rates (0% vs 52.6%, P=0.004), PSA-PFS (median: 1.4 vs 6.0 months, P<0.001), PFS (median: 2.1 vs 6.1 months, P<0.001), and OS (median: 5.5 months vs not reached, P=0.002) compared to AR-V7–negative patients. Similarly, among men receiving abiraterone, AR-V7–positive patients had inferior PSA response rates (0% vs 68.0%, P=0.004), PSA-PFS (median: 1.3 months vs not reached, P<0.001), PFS (median: 2.3 months vs not reached, P<0.001), and OS (median: 10.6 months vs not reached, P=0.006). The negative prognostic impact of AR-V7 was maintained after adjusting for full-length-AR expression. Conclusions. Detection of AR-V7 in CTCs from patients with castration-resistant prostate cancer is associated with resistance to enzalutamide and abiraterone. Overall design: A total of four metastatic castration-resistant prostate tumor samples from four patients were subjected to RNA-seq. Two samples were positive for androgen receptor splice variant 7 and the other two were negative for this variant.
Publication Title
AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
SMARCB1 (Snf5/Ini1/Baf47) is a potent tumor suppressor, the loss of which serves as the diagnostic feature in Malignant Rhabdoid Tumors (MRT) and Atypical Teratoid/Rhabdoid Tumors (AT/RT), two highly aggressive forms of pediatric neoplasms. Here, we restore Smarcb1 expression in cells derived from Smarcb1-deficient tumors which developed in Smarcb1-heterozygous p53-/- mice.
Publication Title
Loss of IGFBP7 expression and persistent AKT activation contribute to SMARCB1/Snf5-mediated tumorigenesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Danio rerio
- 2 Downloadable Samples
- IlluminaHiSeq2000
Description
Purpose: using RNA-seq as a screening tool to determine candidate genes of interest within a genetically defined neural subpopulation in the zebrafish embryonic spinal cord. Results: The early embryonic spinal cord displays patterns of spontaneous activity that generate the earliest motor behavior in the zebrafish. We show the behavior and the neural activity to be inhibited by environmental levels of light. Since at these young ages the fish is blind, and since restricted illumination patterns on the trunk of the fish can elicit a photo-response, we hypothesized that the photo-inhibition is an intrinsic property of the active central pattern generator network within the spinal cord. We FACS-isolated cells from this network as well as those from a panneuronal population and sequenced mRNAs. Through differential expression analysis we identified vertebrate ancient long opsin a as a candidate and then further validated its function in the circuit through knockdown and rescue experiments. Overall design: RNA sequencing of 2 FACS purified neural populations from zebrafish spinal cord.
Publication Title
A spinal opsin controls early neural activity and drives a behavioral light response.
Sample Metadata Fields
No sample metadata fields
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