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GSE48163
Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
HEK293T cells were transfected with the Rbp1-amr or slow (R729H-amr) -amanitin resistant subunit of RNA Pol II and selected with -amanitin 24 hours after transfection for additional 24 hours. Total RNA was extracted and global changes in gene expression were determined using microarray chips.
Publication Title
Disparity between microRNA levels and promoter strength is associated with initiation rate and Pol II pausing.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 3 Downloadable Samples
IlluminaHiSeq2000
Description
When assembling a nephron during development a multipotent stem cell pool becomes restricted as differentiation ensues. A faulty differentiation arrest in this process leads to transformation and initiation of a Wilms'' tumor. Mapping these transitions with respective surface markers affords accessibility to specific cell subpopulations. NCAM1 and CD133 have been previously suggested to mark human renal progenitor populations. Herein, using cell sorting, RNA sequencing, in vitro studies with serum-free media and in vivo xenotransplantation we demonstrate a sequential map that links human kidney development and tumorigenesis; In nephrogenesis, NCAM1+CD133- marks SIX2+ multipotent renal stem cells transiting to NCAM1+CD133+ differentiating segment-specific SIX2- epithelial progenitors and NCAM1-CD133+ differentiated nephron cells. In tumorigenesis, NCAM1+CD133- marks SIX2+ blastema that includes the ALDH1+ WT cancer stem/initiating cells, while NCAM1+CD133+ and NCAM1-CD133+ specifying early and late epithelial differentiation, are severely restricted in tumor initiation capacity and tumor self-renewal. Thus, negative selection for CD133 is required for defining NCAM1+ nephron stem cells in normal and malignant nephrogenesis. Overall design: Human fetal kidney mRNA profiles of 3 cell populations (NCAM1+/CD133-, NCAM+/CD133+, NCAM-/CD133+) were generated by deep sequencing using Illumina HiSeq.
Publication Title
Dissecting Stages of Human Kidney Development and Tumorigenesis with Surface Markers Affords Simple Prospective Purification of Nephron Stem Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Association of juvenile spondyloarthritis (jSpA) with the HLA-B27 genotype is well established, but there is little knowledge of other genetic factors with a role in disease development. The aim of the present study was to identify and confirm gene signatures and novel biomarkers in various cohorts of untreated and treated patients diagnosed with jSpA and other forms of juvenile idiopathic arthritis (JIA).
Publication Title
Aberrant expression of shared master-key genes contributes to the immunopathogenesis in patients with juvenile spondyloarthritis.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Mus musculus
- 14 Downloadable Samples
- IlluminaHiSeq2000
Description
We have employed gene expression profiling in order to identify targets of transcriptional response to stress in resting mouse Swiss 3T3 fibroblasts, either untreated (control) or treated with anisomycin for 3 or 6 hours to induce the p38/MAP kinase pathway. In order determine transcriptional effects dependent on MSK1/2 kinase activity, H89 inhibitor was used in the study. Overall design: Serum starved (72 h 0.2% FCS) mouse 3T3 cells were treated with anisomycin (188.5 nM) for 3 h or 6h (in duplicates) either with or without 15-min pre-treatment with MSK1/2 inhibitor H89 (10 uM). Untreated, serum-starved cells were used as a control. RNA was collected and gene expression profiling using strand-specific RNA-seq was performed.
Publication Title
H3S28 phosphorylation is a hallmark of the transcriptional response to cellular stress.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
We have employed gene expression profiling in order to identify targets of transcriptional response to stress in resting mouse Swiss 3T3 fibroblasts, either untreated (control) or treated with anisomycin to induce the p38/MAP kinase pathway. Overall design: Serum starved (72 h 0.2% FCS) mouse 3T3 cells were treated with anisomycin (188.5 nM) for 1 h (in duplicates). Untreated, serum-starved cells were used as a control. RNA was collected and gene expression profiling using strand-specific RNA-seq was performed.
Publication Title
H3S28 phosphorylation is a hallmark of the transcriptional response to cellular stress.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 21 Downloadable Samples
- Illumina HiSeq 2500
Description
Somatic cancer driver mutations may result in distinctly diverging phenotypic outputs. Thus, a common driver lesion may result in cancer subtypes with distinct clinical presentations and outcomes. The diverging phenotypic outputs of mutations result from the superimposition of the mutations with distinct progenitor cell populations that have differing lineage potential. However, our ability to test this hypothesis has been challenged by currently available tools. For example, flow cytometry is limited in its inability to resolve lineage commitment of early progenitors. Single-cell RNA sequencing (scRNA-seq) may provide higher resolution mapping of the early progenitor populations as long as high throughput technology is available to sequence thousands of single cells. Nevertheless, high throughput scRNA-seq is limited in its inability to jointly and robustly detect the mutational status and the transcriptional profile from the same cell. To overcome these limitations, we propose the use of scRNA-seq combined with targeted mutation sequencing from transcrptional read-outs. Overall design: We apply this method to study myeloid neopasms, in which the comlex process of hematopoiesis is corrupted by mutated stem and progenitor cells.
Publication Title
Somatic mutations and cell identity linked by Genotyping of Transcriptomes.
Sample Metadata Fields
Sex, Age, Disease, Treatment, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Ion Torrent Proton
Description
We searched for roles of ZEB1 during EMT by RNA-seq in breast cancer cells. Overall design: Expression of mRNA in a basal type breast cancer cell line MDA-231-D transfected with ZEB1/ZEB2 siRNAs and stimulated with TGF-beta for 24 h.
Publication Title
ZEB1-regulated inflammatory phenotype in breast cancer cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 138 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Endometriosis, an estrogen-dependent, progesterone-resistant, inflammatory disorder affects 10% of reproductive-age women. It is diagnosed and staged at surgery, resulting in an 11-year latency from symptom onset to diagnosis, underscoring the need for less invasive, less expensive approaches. Since the uterine lining (endometrium) in women with endometriosis has altered molecular profiles, we tested whether molecular classification of this tissue can distinguish and stage disease. We developed classifiers using genomic data from n=148 archived endometrial samples from women with endometriosis or without endometriosis (normal controls or with other common uterine/pelvic pathologies) across the menstrual cycle and evaluated their performance on independent sample sets. Classifiers were trained separately on samples in specific hormonal milieu, using margin tree classification, and accuracies were scored on independent validation samples. Classification of samples from women with endometriosis or no endometriosis involved two binary decisions each based on expression of specific genes. These first distinguished presence or absence of uterine/pelvic pathology and then no endometriosis from endometriosis, with the latter further classified according to severity (minimal/mild or moderate/severe). Best performing classifiers identified endometriosis with 90-100% accuracy, were cycle phase-specific or independent, and utilized relatively few genes to determine disease and severity. Differential gene expression and pathway analyses revealed immune activation, altered steroid and thyroid hormone signaling/metabolism and growth factor signaling in endometrium of women with endometriosis. Similar findings were observed with other disorders versus controls. Thus, classifier analysis of genomic data from endometrium can detect and stage pelvic endometriosis with high accuracy, dependent or independent of hormonal milieu. We propose that limited classifier candidate-genes are of high value in developing diagnostics and identifying therapeutic targets. Discovery of endometrial molecular differences in the presence of endometriosis and other uterine/pelvic pathologies raises the broader biological question of their impact on the steroid hormone response and normal functions of this tissue.
Publication Title
Molecular classification of endometriosis and disease stage using high-dimensional genomic data.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A population of endometrial cells displaying key properties of mesenchymal stem cells (eMSC) has been identified in human endometrium. eMSC co-express CD146 and PDGFRB surface markers, have a perivascular location, and likely represent the reservoir of progenitors giving rise to the endometrial stromal fibroblast lineage. Endometrial stromal cells isolated from 16 oocyte donors and 3 benign gynecologic surgery subjects were FACS sorted into four populations: CD146+/PDGFRB+ (eMSC); CD146+/PDGFRB- (endothelial cells); CD146-/PDGFRB+ (stromal fibroblasts); CD146-/PDGFRB- (mixed population) then subjected to gene expression analysis on Affymetrix Human Gene 1.0 ST arrays, and differentially expressed genes compared between eMSC, stromal fibroblast, and endothelial cell populations. Ninety-two genes were validated by multiplex quantitative RT-PCR on seventy of these sorted cell populations. Immunohistochemistry was used to verify the perivascular location of eMSCs.Principal component analysis and hierarchical clustering showed eMSC clustering discretely near stromal fibroblasts and separately from endothelial cells. eMSC expressed pericyte markers and genes involved hypoxia response, inflammation, proteolysis, and angiogenesis/vasculogenesis all relevant to endometrial tissue breakdown and regeneration. Additionally, eMSC displayed distinct gene profiles for cell-cell communication and regulation of gene expression. Overall, the phenotype of the eMSC is that of a multipotent pericyte responsive to hypoxic, proteolytic, and inflammatory stimuli, able to induce angiogenesis, migrate and differentiate into lineage cells, and potentially respond to estradiol and progesterone. Identifying the pathways and gene families described herein in the context of the endometrial niche, will be valuable in understanding normal and abnormal endometrial development in utero and differentiation in adult uterus.
Publication Title
Perivascular human endometrial mesenchymal stem cells express pathways relevant to self-renewal, lineage specification, and functional phenotype.
Sample Metadata Fields
Age, Specimen part
View Samples- Saccharomyces cerevisiae
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
The extent to which carbon flux is directed towards fermentation vs. respiration differs between cell types and environmental conditions. Understanding the basic cellular processes governing carbon flux is challenged by the complexity of the metabolic and regulatory networks. To reveal the genetic basis for natural diversity in channeling carbon flux, we applied Quantitative Trait Loci analysis by phenotyping and genotyping hundreds of individual F2 segregants of budding yeast that differ in their capacity to ferment the pentose sugar xylulose. Causal alleles were mapped to the RXT3 and PHO23 genes, two components of the large Rpd3 histone deacetylation complex. We show that these allelic variants modulate the expression of SNF1/AMPK-dependent respiratory genes. Our results suggest that over close evolutionary distances, diversification of carbon flow is driven by changes in global regulators, rather than adaptation of specific metabolic nodes. Such regulators may improve the ability to direct metabolic fluxes for biotechnological applications. Overall design: mRNA profiles of S. cerevisiae strain BY4741 with either the RXT3 or PHO23 genes either deleted, replaced by S. cerevisiae T73 allele or replaced by S. cerevisiae PHO23 allele
Publication Title
Natural Diversity in Pentose Fermentation Is Explained by Variations in Histone Deacetylases.
Sample Metadata Fields
Cell line, Subject
View Samples