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GSE54491
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) facilitate breast cancer (BC) metastasis, however stable molecular changes that result as a consequence of these processes remain poorly defined. Therefore, we sought to identify molecular markers that could distinguish tumor cells that had completed the EMT:MET cycle in the hopes of identifying and targeting unique aspects of metastatic tumor outgrowth.Therefore, normal murine mammary gland (NMumG) cells transformed by overexpression of EGFR (NME) cells were cultured in the presence of TGF-beta1 (5 ng/ml) for 4 weeks, at which point TGF-beta1 supplementation was discontinued and the cells were allowed to recover for an additional 4 weeks (Post-TGF-Rec). Total RNA was prepared from unstimulated cells (Pre-TGF) of similar passage and compared by microarray analysis.
Publication Title
Fibroblast growth factor receptor splice variants are stable markers of oncogenic transforming growth factor β1 signaling in metastatic breast cancers.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
Illumina HiSeq 2000, Illumina HiSeq 2500
Description
In humans, the most common sex chromosomal disorder is Klinefelter syndrome (KS), caused by the presence of one or more extra X-chromosomes. The KS patients display a diverse adult phenotype with increased height, gynaecomastia, and hypergonadotropic hypogonadism as the most common symptoms. Men with KS are almost always infertile due to testicular degeneration, which accelerates during puberty. Very few studies investigated when the germ cell loss begins and whether it is caused by dysgenetic fetal development of the testes. We investigated a series of fetal KS testis tissue samples and found a marked reduction in MAGE-A4-positive pre-spermatogonia in the developing KS gonads compared to controls, indicating a failure of the gonocytes to differentiate into pre-spermatogonia. Transcriptome analysis by RNA sequencing of formalin-fixed and paraffin embedded gonads originating from 4 fetal KS samples and 5 age- and cellularity-matched controls revealed 211 differentially expressed transcripts in the fetal KS testis. We found a significant enrichment of upregulated X-chromosomal transcripts and validated the expression of the pseudoautosomal region 1 (PAR1) gene, AKAP17A. Moreover, we found enrichment of long non-coding RNAs in the KS testes (e.g. LINC01569 and RP11-485F13.1). In conclusion, our data indicates that the testicular phenotype observed among adult men with KS is initiated already in fetal life by failure of the gonocyte differentiation into pre-spermatogonia, which could be due to aberrant expression of long non-coding RNAs. Overall design: Includes a total of 9 samples. 4 fetal Klinefelter and 5 age-matched controls testis samples
Publication Title
Transcriptome profiling of fetal Klinefelter testis tissue reveals a possible involvement of long non-coding RNAs in gonocyte maturation.
Sample Metadata Fields
Subject
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
To investigate the role of DNA topoisomerases in transcription, we have studied global gene expression in Saccharomyces cerevisiae cells deficient for topoisomerases I and II and performed single-gene analyses to support our findings. The genome-wide studies show a general transcriptional down-regulation upon lack of the enzymes, which correlates with gene activity but not gene length. Furthermore, our data reveal a distinct subclass of genes with a strong requirement for topoisomerases. These genes are characterized by high transcriptional plasticity, chromatin regulation, TATA box presence, and enrichment of a nucleosome at a critical position in the promoter region, in line with a repressible/inducible mode of regulation. Single-gene studies with a range of genes belonging to this group demonstrate that topoisomerases play an important role during activation of these genes. Subsequent in-depth analysis of the inducible PHO5 gene reveals that topoisomerases are essential for binding of the Pho4p transcription factor to the PHO5 promoter, which is required for promoter nucleosome removal during activation. In contrast, topoisomerases are dispensable for constitutive transcription initiation and elongation of PHO5, as well as the nuclear entrance of Pho4p. Finally, we provide evidence that topoisomerases are required to maintain the PHO5 promoter in a superhelical state, which is competent for proper activation. In conclusion, our results reveal a hitherto unknown function of topoisomerases during transcriptional activation of genes with a repressible/inducible mode of regulation
Publication Title
DNA Topoisomerases maintain promoters in a state competent for transcriptional activation in Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The pesticide rotenone, a neurotoxin that inhibits the mitochondrial complex I, and destabilizes microtubules (MT) has been linked to Parkinson disease (PD) etiology and is often used to model this neurodegenerative disease (ND). Many of the mechanisms of action of rotenone are posited mechanisms of neurodegeneration; however, they are not fully understood. Therefore, the study of rotenone-affected functional pathways is pertinent to the understanding of NDs pathogenesis. This report describes the transcriptome analysis of a neuroblastoma (NB) cell line chronically exposed to marginally toxic and moderately toxic doses of rotenone. The results revealed a complex pleiotropic response to rotenone that impacts a variety of cellular events, including cell cycle, DNA damage response, proliferation, differentiation, senescence and cell death, which could lead to survival or neurodegeneration depending on the dose and time of exposure and cell phenotype. The response encompasses an array of physiological pathways, modulated by transcriptional and epigenetic regulatory networks, likely activated by homeostatic alterations. Pathways that incorporate the contribution of MT destabilization to rotenone toxicity are suggested to explain complex I-independent rotenone-induced alterations of metabolism and redox homeostasis. The postulated mechanisms involve the blockage of mitochondrial voltage-dependent anions channels (VDACs) by tubulin, which coupled with other rotenone-induced organelle dysfunctions may underlie many presumed neurodegeneration mechanisms associated with pathophysiological aspects of various NDs including PD, AD and their variant forms. Thus, further investigation of such pathways may help identify novel therapeutic paths for these NDs.
Publication Title
Transcriptome analysis of a rotenone model of parkinsonism reveals complex I-tied and -untied toxicity mechanisms common to neurodegenerative diseases.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Danio rerio
- 9 Downloadable Samples
- IlluminaHiSeq2500
Description
Goal of this study is differential gene expression between wild type and MZnanog mutant during early zebrafish embryogenesis Overall design: Three timepoints - 2 hours post fertilization (hpf), 4 hpf, and 6.5 hpf; two replicates of wild type at each time point, one replicate for MZnanog at each time point
Publication Title
The primary role of zebrafish <i>nanog</i> is in extra-embryonic tissue.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
- Illumina HiSeq 2000
Description
In humans, the most common sex chromosomal disorder is Klinefelter syndrome (KS), caused by the presence of one or more extra X-chromosomes. The KS patients display a diverse adult phenotype with increased height, gynaecomastia, and hypergonadotropic hypogonadism as the most common symptoms. Men with KS are almost always infertile due to testicular degeneration, which accelerates during puberty. Very few studies investigated the global gene expression analysis of adult KS testes and, more importantly, which cell types the differentially expressed transcripts originate from. Transcriptome analysis by RNA sequencing of fixed and paraffin embedded testes originating from 3 adult KS samples and 3 adult cellularity-matched controls revealed 236 differentially expressed transcripts in the adult KS testis. To examine the cellular origin of the differentially expressed transcripts, transcriptome profiling was also carried out on 4 testes with Sertoli Cell-Only and 4 testes with full spermatogenesis. Also, pre-pubertal KS and controls were RNA-sequenced. Overall design: Includes a total of 22 testis samples. 3 adult Klinefelter, 3 Klinefelter-like, 4 Sertoli Cell-Only, 4 with full spermatogenesi, 4 pre-pubertal Klinefelter and 4 pre-pubertal controls
Publication Title
Transcriptome analysis of the adult human Klinefelter testis and cellularity-matched controls reveals disturbed differentiation of Sertoli- and Leydig cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Danio rerio
- 1138 Downloadable Samples
- NextSeq 500
Description
The identification of cell types and marker genes is critical for dissecting neural development and function, but the size and complexity of the brain has hindered the comprehensive discovery of cell types. We combined single-cell RNA-seq with anatomical brain registration to create a comprehensive map of the zebrafish habenula, a conserved forebrain hub involved in pain processing and learning. Single-cell transcriptomes of ~13000 habenular cells (>4x coverage) identified 18 neuronal types and dozens of marker genes. Registration of marker genes onto a common reference atlas created a rich resource for anatomical and functional studies and enabled the mapping of active neurons onto neuronal types following aversive stimuli. Strikingly, despite brain growth and functional maturation, cell types were retained between the larval and adult habenula. This study provides a gene expression atlas to dissect habenular development and function and offers a general framework for the comprehensive characterization of other brain regions. Overall design: gng8-GFP zebrafish heads were dissected, dissociated and FAC sorted into 96 well plates. Single cell libraries were generated in batches of 384 cells using Smart-seq2. A total of 22 gng8-GFP fish were dissected in 3 batches and 384 cells were processed from each using Smart-seq2.
Publication Title
Comprehensive Identification and Spatial Mapping of Habenular Neuronal Types Using Single-Cell RNA-Seq.
Sample Metadata Fields
Specimen part, Subject
View Samples- Danio rerio
- 1138 Downloadable Samples
- Illumina HiSeq 2500
Description
Spatial localization is a key determinant of cellular fate and behavior, but spatial RNA assays traditionally rely on staining for a limited number of RNA species. In contrast, single-cell RNA-seq allows for deep profiling of cellular gene expression, but established methods separate cells from their native spatial context. Here we present Seurat, a computational strategy to infer cellular localization by integrating single-cell RNA-seq data with in situ RNA patterns. We applied Seurat to spatially map 851 single cells from dissociated zebrafish (Danio rerio) embryos, inferring a transcriptome-wide map of spatial patterning. We confirmed Seurat’s accuracy using several experimental approaches, and used it to identify a set of archetypal expression patterns and spatial markers. Additionally, Seurat correctly localizes rare subpopulations, accurately mapping both spatially restricted and scattered groups. Seurat will be applicable to mapping cellular localization within complex patterned tissues in diverse systems. Overall design: We generated single-cell RNA-seq profiles from dissociated cells from developing zebrafish embryos (late blastula stage - 50% epiboly)
Publication Title
Spatial reconstruction of single-cell gene expression data.
Sample Metadata Fields
Subject
View Samples- Danio rerio
- 415 Downloadable Samples
- Illumina HiSeq 2500
Description
SMART-seq2 was performed on single cells isolated from visually staged zebrafish embryos. Overall design: Samples were all sequenced in one batch. Some were generated with a 5'' UMI-tagged method, and others are full-length SMART-seq2.
Publication Title
Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis.
Sample Metadata Fields
Subject
View Samples- Danio rerio
- 28 Downloadable Samples
- NextSeq 500
Description
Wild-type zebrafish embryos were mechanically dissociated and profiled using Drop-seq Overall design: Drop-seq was performed on 28 groups of 20-40 visually staged, mechanically dissociated embryos. Samples were combined and sequenced in batches DS2-DS5.
Publication Title
Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis.
Sample Metadata Fields
Subject
View Samples