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SRP020493
Homo sapiens
14 Downloadable Samples
Illumina HiSeq 2000
Description
Recurrent mutations in histone modifying enzymes in multiple cancer types imply key roles in tumorigenesis. However, the functional relevance of these mutations remains unknown. Here we show that the JARID1B histone H3 lysine 4 demethylase is frequently amplified and overexpressed in luminal breast tumors and a somatic point mutation of JARID1B leads to the gain of luminal-specific gene expression programs. Downregulation of JARID1B in luminal breast cancer cells induces the expression of basal cell-specific genes and growth arrest, which is partially rescued by the inhibition of TGFBR thereby indicating a key role for TGFb signaling. Integrated genome-wide analysis of JARID1B chromatin binding, histone H3 lysine trimethyl (H3K4me3) and dimethyl (H3K4me2) patterns, and gene expression profiles in luminal and basal-like breast cancer cells suggest a key role for JARID1B in luminal cell-specific gene expression programs. A significant fraction of JARID1B binding-sites overlaps with CTCF in both luminal and basal-like breast cancer cells. CTCF also co-immunoprecipitates with JARID1B and it may influence its histone demethylase (HDM) activity as the H3K4me3/me2 ratio is lower at the CTCF-overlapping compared to JARID1B-unique sites. Additionally, a heterozygous JARID1B missense mutation (K1435R) in the HCC2157 basal-like breast cancer cell line is associated with unique JARID1B chromatin-binding and gene expression patterns implying gain of luminal features. In line with this, exogenous expression of this mutant in basal-like breast cancer cells leads to a gain of JARID1B binding at many luminal-specific genes. A PARADIGM score reflecting JARID1B activity in luminal breast cancer cells is associated with poor clinical outcome in patients with luminal breast tumors. Together, our data imply that JARID1B is a luminal lineage-driving oncogene and that its therapeutic targeting may represent a novel therapeutic strategy in treatment-resistant luminal breast tumors. Overall design: RNA-Seq in breast cancer cell-lines transfected with JARID1B/CTCF/control siRNA. 50 cycles of sequencing on Illumina platform.
Publication Title
JARID1B is a luminal lineage-driving oncogene in breast cancer.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The estrogen-dependence of breast cancer has long been recognized, however, the role of 17-estradiol (E2) in cancer initiation was not known until we demonstrated that it induces complete neoplastic transformation of the human breast epithelial cells MCF-10F. E2-treatment of MCF-10F cells progressively induced high colony efficiency and loss of ductulogenesis in early transformed (trMCF) cells and invasiveness in Matrigel invasion chambers. The cells that
Publication Title
Epithelial to mesenchymal transition in human breast epithelial cells transformed by 17beta-estradiol.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 110 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
It is widely accepted that a womans lifetime risk of developing breast cancer at menopause is reduced by early full term pregnancy and multiparity. This phenomenon is associated with the development and differentiation of the breast, which ultimately imprints a specific genomic profile in the mammary epithelium. In the present work we demonstrate that this profile represents a permanent signature that could be associated with the breast cancer risk reduction conferred by pregnancy.
Publication Title
Defining the genomic signature of the parous breast.
Sample Metadata Fields
No sample metadata fields
View Samples- Oryza sativa
- 9 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Sperm cells represent the male partner that fuses with the egg cell during fertilization in all multi-cellular eukaryotic organisms, and, in flowering plants, is a founder of both embryo and nutritive endosperm. We examined the transcriptome of Oryza sativa ssp. japonica using the Affymetrix 57K rice genome GeneChip to provide an overview of genes activated in the paternal gamete.
Publication Title
Transcriptome-based examination of putative pollen allergens of rice (Oryza sativa ssp. japonica).
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Illumina HiSeq 2500
Description
Viral infection can dramatically alter a cell''s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in production of viral gene transcripts -- viral transcripts compose less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, and this gene absence partially explains variation in viral transcriptional load. Despite variation in total viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells. Overall design: Dataset consists of a total of five single-cell datasets generated using the 10x Genomics Chromium Single Cell 3'' Solution platform. All samples were generated from a tissue culture infection model using A549 cells from ATCC and Influenza A/WSN/1933 virus. Uninfected control sample identically processed. Infected samples were generated from cells infected for 6, 8, and 10 hours with a single replicate at 8 hours.
Publication Title
Extreme heterogeneity of influenza virus infection in single cells.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Induction of hepatocellular carcinoma by in vivo gene targeting.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
C/EBPbeta-2 results in EMT and ErbB indpendence this project investigated the gene changes in related genes upon C/EBPbeta-2 overexpression in MCF10A cells.
Publication Title
Genomic profiling of C/EBPβ2 transformed mammary epithelial cells: a role for nuclear interleukin-1β.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
The distinct phenotypic and prognostic subclasses of human hepatocellular carcinoma (HCC) are difficult to reproduce in animal experiments. Here we have used in vivo gene targeting to insert an enhancer-promoter element at an imprinted chromosome 12 locus in mice, thereby converting ~1 in 20,000 normal hepatocytes into a focus of HCC with a single genetic modification. A 300 kb chromosomal domain containing multiple mRNAs, snoRNAs and microRNAs was activated surrounding the integration site. An identical domain was activated at the syntenic locus in a specific molecular subclass of spontaneous human HCCs with a similar histological phenotype, which was associated with partial loss of DNA methylation. These findings demonstrate the accuracy of in vivo gene targeting in modeling human cancer, and suggest future applications in studying various tumors in diverse animal species. In addition, similar insertion events produced by randomly integrating vectors could be a concern for liver-directed human gene therapy.
Publication Title
Induction of hepatocellular carcinoma by in vivo gene targeting.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 150 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cross-study homogeneity of psoriasis gene expression in skin across a large expression range.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 79 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
cDNA and cRNA hybridization technologies have different, probe-specific sensitivities. We used samples from an etanercept trial (GSE11903) to explore in a real-life setting the uniqueness of each platform.
Publication Title
Cross-study homogeneity of psoriasis gene expression in skin across a large expression range.
Sample Metadata Fields
Specimen part, Time
View Samples