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GSE25639
Mus musculus, Homo sapiens
113 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 96 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Attempts at modeling chromosomal translocations involving MALT1 gene, hallmarks of human mucosa-associated lymphoid tissue (MALT) lymphoma, have failed to reproduce the disease in mice. Here we describe a transgenic model in which MALT1 expression was targeted to mouse hematopoietic stem/progenitor cells. In Sca1-MALT1 mice, MALT1 deregulation activated the NF-kappaB pathway in Sca1+ cells, promoting selective B-cell differentiation and mature lymphocyte accumulation in extranodal tissues, progressively leading to the development of clonal B-cell lymphomas. These tumors recapitulated the histopathological features of human MALT lymphomas, presenting typical lymphoepithelial lesions and plasmacytic differentiation. Transcriptional profiling of Sca1-MALT1 murine lymphomas revealed overlapping molecular signatures with human MALT lymphomas, including MALT1-mediated NF-kappaB activation, pro-inflammatory signaling and XBP1-induced plasmacytic differentiation. Moreover, murine Malt1 showed proteolytic activity by cleaving Bcl10 in Sca1-MALT1 lymphomas. Our novel technological approach has allowed modeling human MALT lymphoma in mice, which represent unique tools study MALT lymphoma biology and evaluate anti-MALT1 therapies.
Publication Title
Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 10 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Comparison of gene expression profiling analysis of bone marrow isolated CD34+ cells from patients with MALT lymphoma vs. healthy individuals revealed a large number of differentially expressed genes that included NF-kB target genes, genes involved in inflamatory signalling and immunoglobulin genes, suggesting an early lymphoid B-cell priming.
Publication Title
Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Attempts at modeling chromosomal translocations involving MALT1 gene, hallmarks of human mucosa-associated lymphoid tissue (MALT) lymphoma, have failed to reproduce the disease in mice. Here we describe a transgenic model in which MALT1 expression was targeted to mouse hematopoietic stem/progenitor cells. In Sca1-MALT1 mice, MALT1 deregulation activated the NF-kappaB pathway in Sca1+ cells, promoting selective B-cell differentiation and mature lymphocyte accumulation in extranodal tissues, progressively leading to the development of clonal B-cell lymphomas. These tumors recapitulated the histopathological features of human MALT lymphomas, presenting typical lymphoepithelial lesions and plasmacytic differentiation. Transcriptional profiling of Sca1-MALT1 murine lymphomas revealed overlapping molecular signatures with human MALT lymphomas, including MALT1-mediated NFkappaB activation, pro-inflammatory signaling and XBP1-induced plasmacytic differentiation. Moreover, murine Malt1 showed proteolytic activity by cleaving Bcl10 in Sca1-MALT1 lymphomas. Our novel technological approach has allowed modeling human MALT lymphoma in mice, which represent unique tools study MALT lymphoma biology and evaluate anti-MALT1 therapies.
Publication Title
Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 14 Downloadable Samples
Description
Major roadblocks to developing effective progesterone receptor (PR)-targeted therapies in breast cancer include the lack of highly-specific PR modulators, a poor understanding of the pro- or anti-tumorigenic networks for PR isoforms and ligands, and an incomplete understanding of the cross talk between PR and estrogen receptor (ER) signaling. Through genomic analyses of xenografts treated with various clinically-relevant ER and PR-targeting drugs, we describe how the activation or inhibition of PR dictates distinct ER and PR chromatin binding and differentially reprograms estrogen signaling, resulting in the segregation of transcriptomes into separate PR agonist and antagonist-mediated groups. These findings address an ongoing controversy regarding the clinical utility of PR agonists and antagonists, alone or in combination with tamoxifen, for breast cancer management. Genomic analyses of the two PR isoforms, PRA and PRB, indicate that these isoforms bind distinct genomic sites and interact with different sets of co-regulators to differentially modulate gene expression as well as pro- or anti-tumorigenic phenotypes. Of the two isoforms, PRA inhibited gene expression and ER chromatin binding significantly more than PRB. Of note, the two isoforms reprogrammed estrogen activity to be either pro or anti-tumorigenic. In concordance to the in-vitro observations, differential gene expression was observed in PRA and PRB-rich patient tumors and importantly, PRA-rich gene signatures had poorer survival outcomes. In support of antiprogestin responsiveness of PRA-rich tumors, gene signatures associated with PR antagonists, but not PR agonists, predicted better survival outcomes. This differential of better patient survival associated with PR antagonists versus PR agonists treatments was further reflected in the higher anti-tumor activity of combination therapies of tamoxifen with PR antagonists and modulators. Knowledge of various determinants of PR action and their interactions with estrogen signaling to differentially modulate breast cancer biology should serve as a guide to the development of biomarkers for patient selection and translation of PR-targeted therapies to the clinic. Overall design: For in-vitro experiments, cells were grown in steroid-deprived RPMI for 48 hours to 80% confluence, before being treated for with the hormones of interest (vehicle, 10 nM estrogen, 10 nM R5020 or both estrogen +R5020). Cells were then fixed with 1% formaldehyde for 10 minutes and the crosslinking was quenched with 0.125 M glycine for 5 minutes. Fixed cells were suspended in ChIP lysis buffer (1 ml 1M Tris pH 8.0; 200 µl 5M NaCl; 1 ml 0.5M EDTA; 1 ml NP-40; 1 g SDS, 0.5 g deoxycholate) and sheared in the Diagenode Biorupter for 20 minutes (30 second cycles). 100 µl of sheared chromatin was removed as input control. A 1:10 dilution of sheared chromatin in ChIP dilution buffer (1.7 ml 1M Tris pH 8.0; 3.3 ml 5M NaCl; 5 ml 10% NP-40; 200 µl 10% SDS; to 100 ml with H2O), 4 µg antibody and 30 µl magnetic DynaBeads were incubated in a rotator at 4oC overnight. Chromatin was immunoprecipitated overnight using anti-ER (Santa Cruz Biotechnology HC-20), anti-PR (in-house made KD68) or rabbit IgG (Santa Cruz Biotechnology SC-2027). Next, the immunoprecipitated chromatin was washed with ChIP wash buffer I (2 ml 1M Tris pH 8.0; 3 ml 5M NaCl; 400 µl 0.5M EDTA; 10 ml 10% NP-40; 1 ml 10% SDS; to 100 ml with H2O), ChIP wash buffer II (2 ml 1M Tris pH 8.0; 10 ml 5M NaCl; 400 µl 0.5M EDTA; 10 ml 10% NP-40; 1 ml 10% SDS; to 100 ml with H2O), ChIP wash buffer III (1 ml 1M Tris pH 8.0; 5 ml of 5M LiCl; 200 µl 0.5M EDTA; 10 ml 10% NP-40; 10 ml 10% deoxycholate; to 100 ml with H2O) and TE (pH 8.0). Elution was performed twice from beads by incubating them with 100 µl ChIP-elution buffer (1% SDS, 0.1 M NaHCO3) at 65oC for 15 minutes each. The eluted protein-DNA complexes were de-crosslinked overnight at 65oC in 200 µM NaCl. After de-crosslinking, the mixture was treated with proteinase K for 45 minutes followed by incubation with RNase A for 30 minutes. Finally, DNA fragments were purified using Qiagen PCR purification kit and reconstituted in 50 µl nuclear-free water. Real time PCR was performed using SYBR green. For ChIP-seq library preparations, libraries were prepared using KapaBiosystems LTP library preparation kit (#KK8232) according to the manufacturer's protocol.
Publication Title
Progesterone receptor isoforms, agonists and antagonists differentially reprogram estrogen signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 8 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
In Saccharomyces cerevisiae, the maturation of both pre-rRNA and pre-small nucleolar RNAs (pre-snoRNAs) involves common factors, thereby providing a potential mechanism for the coregulation of snoRNA and rRNA synthesis. In this study, we examined the global impact of the double-stranded-RNA-specific RNase Rnt1p, which is required for pre-rRNA processing, on the maturation of all known snoRNAs. In silico searches for Rnt1p cleavage signals, and genome-wide analysis of the Rnt1p-dependent expression profile, identified seven new Rnt1p substrates. Interestingly, two of the newly identified Rnt1p-dependent snoRNAs, snR39 and snR59, are located in the introns of the ribosomal protein genes RPL7A and RPL7B. In vitro and in vivo experiments indicated that snR39 is normally processed from the lariat of RPL7A, suggesting that the expressions of RPL7A and snR39 are linked. In contrast, snR59 is produced by a direct cleavage of the RPL7B pre-mRNA, indicating that a single pre-mRNA transcript cannot be spliced to produce a mature RPL7B mRNA and processed by Rnt1p to produce a mature snR59 simultaneously. The results presented here reveal a new role of yeast RNase III in the processing of intron-encoded snoRNAs that permits independent regulation of the host mRNA and its associated snoRNA.
Publication Title
Genome-wide prediction and analysis of yeast RNase III-dependent snoRNA processing signals.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 54 Downloadable Samples
- NextSeq 500
Description
Transcriptionally similar subpopulations of exhausted CD8+ T-cells are found in chronic viral infection and tumors Overall design: RNA-seq analysis of progenitor exhausted and terminally exhausted CD8+ T-cells isolated from spleens of mice chronically infected with LCMV Clone 13 (day 30 post-infection) or isolated from B16-ova tumors (day 22 post tumor implantation), with or without anti-PD-1 treatment
Publication Title
Subsets of exhausted CD8<sup>+</sup> T cells differentially mediate tumor control and respond to checkpoint blockade.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- NextSeq 500
Description
Distinct populations of progenitor exhausted (Tcf1+Tim-3-) and terminally exhausted (Tcf1-Tim-3+) CD8+ T-cells occur in B16-OVA tumors Overall design: Profiling of CD8+ T-cells from day 10 and day 20 B16-OVA mouse melanoma tumors
Publication Title
Subsets of exhausted CD8<sup>+</sup> T cells differentially mediate tumor control and respond to checkpoint blockade.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Identification of genes involved in ocular birth defects remains a challenge. To facilitate the identification of genes associated with cataract, we developed iSyTE (integrated Systems Tool for Eye gene discovery; http://bioinformatics.udel.edu/Research/iSyTE). iSyTE contains microarray gene expression profiles of the mouse embryonic lens as it transitions from the stage of placode invagination to that of vesicle formation. We identified differentially regulated genes by comparing lens microarray profiles to those representing whole embryonic body (WB) without ocular tissue. These were then utilized to generate a ranked list of lens-genes enrichment, which can be viewed as iSyTE tracks in the UCSC Genome browser to aid identification of genes with lens function.
Publication Title
iSyTE: integrated Systems Tool for Eye gene discovery.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- IlluminaHiSeq2000
Description
The paired-end next-generation sequencing of all small RNAs of less than 200 nucleotides in length from four different human cell lines (SKOV3ip1, MCF-7, BJ-Tielf, INOF) allowed us to determine the exact sequence(s) and variations of human box C/D snoRNAs (small nucleolar RNAs), revealing processing patterns of this class of molecules. Two distinct groups of box C/D snoRNAs were identified based on the position of their ends with respect to their characteristic boxes and the terminal base pairing potential. Short box C/D snoRNAs start sharply 4 or 5 nucleotides upstream of their box C and end 2 or 3 nucleotides downstream of their box D. In contrast, long box C/D snoRNAs start 5 or 6 nucleotides upstream of their box C and end 4 or 5 nucleotides downstream of their box D, increasing the likelihood of formation of a k-turn between their boxes C and D. Sequencing of SKOV3ip1 cells following the depletions of NOP58, a core box C/D snoRNA-binding protein and of RBFOX2, a splicing factor, shows that the short box C/D snoRNA forms are significantly more affected by the depletion of RBFOX2 while the long snoRNA forms, which display more canonical box C/D snoRNA features, are significantly more affected by the depletion of NOP58. Together the data suggest that box C/D snoRNAs are divided into at least two groups of RNA with distinct maturation and functional preferences. Overall design: Small RNAs (<200 nucleotides) were isolated from different human cell lines that were either untreated or depleted of NOP58 or RBFOX2 using specific siRNAs. The resulting libraries were multiplexed and paired-end sequenced using Illumina HiSeq.
Publication Title
Simultaneous sequencing of coding and noncoding RNA reveals a human transcriptome dominated by a small number of highly expressed noncoding genes.
Sample Metadata Fields
No sample metadata fields
View Samples