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SRP044298
Homo sapiens
10 Downloadable Samples
IlluminaHiSeq2000
Description
UBL5 is an atypical ubiquitin-like protein, whose function in metazoans remains largely unexplored. We show that UBL5 is required for sister chromatid cohesion maintenance in human cells. UBL5 primarily associates with spliceosomal proteins, and UBL5 depletion decreases pre-mRNA splicing efficiency, leading to globally enhanced intron retention. Defective sister chromatid cohesion is a general consequence of dysfunctional pre-mRNA splicing, resulting from the selective downregulation of the cohesion protection factor Sororin. As the UBL5 yeast orthologue, Hub1, also promotes spliceosome functions, our results show that UBL5 plays an evolutionary conserved role in pre-mRNA splicing, the integrity of which is essential for the fidelity of chromosome segregation. Overall design: Total RNA was extracted from HeLa cells treated with control (CTRL), UBL5 (#57, #58, or #82), or SART1 siRNAs for 48 h and processed for RNA-Seq analysis
Publication Title
UBL5 is essential for pre-mRNA splicing and sister chromatid cohesion in human cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 51 Downloadable Samples
Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Time-course and concentration-effect experiments with multiple time points and drug concentrations provide far more valuable information than experiments with just two design-points (treated vs. control), as commonly performed in most microarray studies. Analysis of the data from such complex experiments, however, remains a challenge. Here we present a semi-automated method for fitting time profiles and concentration-effect patterns, simultaneously, to gene expression data. The submodels for time-course included exponential increase and decrease models with parameters such as initial expression level, maximum effect, and rate-constant (or half-time). The submodel for concentration-effect was a 4-parameter Hill model.
Publication Title
Simultaneous modeling of concentration-effect and time-course patterns in gene expression data from microarrays.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 80 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
The earliest recognizable stages of breast neoplasia are lesions that represent a heterogeneous collection of epithelial proliferations currently classified based on morphology. Their role in the development of breast cancer is not well understood but insight into the critical events at this early stage will improve efforts in breast cancer detection and prevention. These microscopic lesions are technically difficult to study so very little is known about their molecular alterations. To characterize the transcriptional changes of early breast neoplasia, we sequenced 3''- end enriched RNAseq libraries from formalin-fixed paraffin-embedded tissue of early neoplasia samples and matched normal breast and carcinoma samples from 25 patients. We find that gene expression patterns within early neoplasias are distinct from both normal and breast cancer patterns and identify a pattern of pro-oncogenic changes, including elevated transcription of ERBB2, FOXA1, and GATA3 at this early stage. We validate these findings on a second independent gene expression profile data set generated by whole transcriptome sequencing. Measurements of protein expression by immunohistochemistry on an independent set of early neoplasias confirms that ER pathway regulators FOXA1 and GATA3, as well as ER itself, are consistently upregulated at this early stage. The early neoplasia samples also demonstrate coordinated changes in long non-coding RNA expression and microenvironment stromal gene expression patterns. This study is the first examination of global gene expression in early breast neoplasia, and the genes identified here represent candidate participants in the earliest molecular events in the development of breast cancer. Overall design: 3SEQ was performed on 72 FFPE human breast samples from 25 patients: 24 normal, 25 early neoplasia, 9 carcinoma in situ, and 14 invasive cancer
Publication Title
A shared transcriptional program in early breast neoplasias despite genetic and clinical distinctions.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
We report the expression profiles of MCF10A cells encapsulated in hydrogels of varying stiffness and composition. Cells were encapsulated for 7 days in either 1.) soft alginate and reconstituted basement membrane (rBM), 2.) stiff alginate and rBM, 3,) soft col-1 and rBM, or 4.) stiff col-1. We find global gene expression changes in response to enhanced ECM stiffness, independent of expression changes in response to col-1 exposure. These results provide a comprehensive study of the gene expression changes associated with increased ECM stiffness in addition to the gene expression changes associated with increased col-1 concentration in combination with, and independent of, ECM stiffness. Overall design: Expression profiling of MCF10A cells in four hydrogel conditions were sequenced in duplicate via Illumina HiSeq.
Publication Title
YAP-independent mechanotransduction drives breast cancer progression.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The Grainyhead family of transcription factors controls morphogenesis and differentiation of epithelial cell layers in multicellular organisms by regulating cell junction- and proliferation-related genes. Grainyhead-like 2 (Grhl2) is expressed in developing mouse lung epithelium and is required for normal lung organogenesis. The specific epithelial cells expressing Grhl2 and the genes regulated by Grhl2 in normal lungs are mostly unknown. In these studies, we identified the NK2 homeobox 1 transcription factor (Nkx2-1) as a direct transcriptional target of Grhl2. By binding and transcriptional assays, and by confocal microscopy we showed that these two transcription factors form a positive feed-back loop in vivo and in cell lines, and are co-expressed in lung bronchiolar and alveolar type II cells. The morphological changes observed in flattening lung alveolar type II cells in culture are associated with down-regulation of Grhl2 and Nkx2-1. Reduction of Grhl2 in lung epithelial cell lines results in lower expression levels of Nkx2-1 and of known Grhl2 target genes. By microarray analysis we identified that in addition to Cadherin1 and Claudin4, Grhl2 regulates other cell interaction genes such as semaphorins and their receptors, which also play a functional role in developing lung epithelium. Impaired collective cell migration observed in Grhl2 knockdown cell monolayers is associated with reduced expression of these genes and may contribute to the altered epithelial phenotype reported in Grhl2 mutant mice. Thus, Grhl2 functions at the nexus of a novel regulatory network, connecting lung epithelial cell identity, migration and cell-cell interactions.
Publication Title
The transcription factors Grainyhead-like 2 and NK2-homeobox 1 form a regulatory loop that coordinates lung epithelial cell morphogenesis and differentiation.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 224 Downloadable Samples
- Illumina HiSeq 2000
Description
Transcriptional profiling of murine dendritic cells stimulated with LPS and IFNg after shRNA knockdown of redox regulators. Overall design: shRNA targeting redox regulators were delivered to bone marrow derived dendritic cells. Cells were stimulated with LPS and IFNg prior to transcriptional profiling by RNAseq over a time course. Each sample sequenced on two Illumina lanes.
Publication Title
Nitric Oxide Engages an Anti-inflammatory Feedback Loop Mediated by Peroxiredoxin 5 in Phagocytes.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Sialic acids on vertebrate cell surfaces mediate many biological roles. Altered expression of certain sialic acid types or their linkages can have prognostic significance in human cancer. A classic but unexplained example is enhanced 2-6-sialylation on N-glycans, resulting from over-expression of the Golgi enzyme -galactoside:2-6-sialyltransferase (ST6Gal-I). Previous data supporting a role for the resulting Sia2-3Gal1-4GlcNAc (Sia6LacNAc) structure in tumor biology were based on in vitro studies in transfected carcinoma cells, in which increased Sia6LacNAc on 1-integrins enhanced their binding to ligands, and stimulated cell motility. Here we examine for the first time the in vivo role of the ST6Gal-I enzyme in the growth and differentiation of spontaneous mammary cancers in mice transgenic for an MMTV-promoter-driven polyoma-middle-T antigen, a tumor in which beta1-integrin function is important for tumorigenesis, and in maintaining the proliferative state of tumor cells. Tumors induced in St6gal1 null animals were more differentiated in comparison to those in the wild-type background, both by histological analysis and by protein expression profiles. Furthermore, we show the St6gal1 null tumors have selectively altered expression of genes associated with focal adhesion signaling, and have decreased phosphorylation of FAK, a downstream target of 1-integrins. This first in vivo evidence for a role of ST6Gal-I in tumor progression was confirmed using a novel approach, which conditionally restored St6gal1 in cell lines derived from the null tumors. These findings indicate a role for ST6Gal-I as a mediator of tumor progression, with its expression causing a less differentiated phenotype, via enhanced 1-integrin function.
Publication Title
alpha 2-6-Linked sialic acids on N-glycans modulate carcinoma differentiation in vivo.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 25 Downloadable Samples
- Illumina HiSeq 4000
Description
mRNA profiles of 8 weeks old C57BL/6 mice 2 days after infections with 5e7 pfu of various strains of murine norovirus (MNV) or 1e8 pfu of T1L reovirus were evauated Overall design: mRNA profiles of 8 weeks old C57BL/6 mice 2 days after infections with 5e7 pfu of various strains of murine norovirus (MNV) or 1e8 pfu of T1L reovirus were evauated
Publication Title
Murine Norovirus Infection Induces T<sub>H</sub>1 Inflammatory Responses to Dietary Antigens.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The goal of this study was to identify potential genes regulated by ERG
Publication Title
Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Human Promoter 1.0R Array (hsprompr)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Consolidation of the cancer genome into domains of repressive chromatin by long-range epigenetic silencing (LRES) reduces transcriptional plasticity.
Sample Metadata Fields
Specimen part, Cell line
View Samples