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GSE39788
Rattus norvegicus
10 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
We are using the ACI rat model of 17beta-estradiol induced mammary cancer to define the mechanisms through which estrogens contribute to breast cancer development; identify and functionally characterize the genetic variants that determine susceptibility; and define the hormone-gene-environment interactions that influence development of mammary cancer in this physiologically relevant rat model. Female ACI rats are uniquely susceptible to development of mammary cancer when treated continuously with physiologic levels of 17beta-estradiol. Induction of mammary cancer in female ACI rats occurs through a mechanism that is largely dependent upon estrogen receptor-alpha. Interval mapping analyses of progeny generated in intercrosses between susceptible ACI rats and resistant Brown Norway (BN) rats revealed seven quantitative trait loci (QTL), designated Emca3 (Estrogen-induced mammary cancer) through Emca9, each of which harbors one or more genetic determinants of mammary cancer susceptibility. Genes that reside within Emca8 on RNO5 and were differentially expressed between 17beta-estradiol treated ACI and ACI.BN-Emca8 congenic rats were identified as Emca8 candidates.
Publication Title
Mapping of three genetic determinants of susceptibility to estrogen-induced mammary cancer within the Emca8 locus on rat chromosome 5.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 53 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This study demonstrates that siRNA off-targets (e.g. 3'UTR off-targets), can be significantly reduced when cells are treated with a relatively low dose of siRNA (e.g. 1nM) that is sufficient to effectively silence the intended target.
Publication Title
siRNA off-target effects can be reduced at concentrations that match their individual potency.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
Tight regulation of hematopoietic stem cell (HSC) homeostasis is essential for life-long hematopoiesis, for preventing blood cancers and for averting bone marrow failure. The underlying mechanisms are incompletely understood. Here, we identify production of inositol-tetrakisphosphate (IP4) by inositoltrisphosphate 3-kinase B (ItpkB) as essential for HSC quiescence and function. Young ItpkB-/- mice accumulated phenotypic HSC and showed extramedullary hematopoiesis. ItpkB-/- HSC were less quiescent and proliferated more than wildtype controls. They downregulated quiescence and stemness associated mRNAs, but upregulated activation, oxidative metabolism, protein synthesis and lineage associated transcripts. Although they showed no significant homing defects, ItpkB-/- HSC had a severely reduced competitive long-term repopulating potential. Aging ItpkB-/- mice lost hematopoietic stem and progenitor cells and died with severe anemia. Wildtype HSC normally repopulated ItpkB-/- hosts, incidating a HSC-intrinsic ItpkB requirement. ItpkB-/- HSC had reduced cobblestone-area forming cell activity in vitro and showed increased stem-cell-factor activation of the phosphoinositide 3-kinase (PI3K) effector Akt, reversed by exogenous provision of the known PI3K/Akt antagonist IP4. They also showed transcriptome changes consistent with hyperactive Akt/mTOR signaling. Thus, we propose that ItpkB ensures HSC quiescence by limiting cytokine-induced PI3K signaling in HSC. Overall design: For each of 3 replicate ItpkB-/- or wt samples, we enriched Lin- cells from BM of 4 pooled age-matched mice with Rapidspheres (Stemcell Technologies), FACS-sorted =10,000 LSK CD34-CD150+CD48-Flk2- LT-HSC into lysis buffer and prepared RNA with RNeasy Micro kits (Quiagen). RNA sequencing was done using an Illumina HISeq Analyzer 2000, Casava v1.8.2 genome analyzer pipeline, TopHat v1.4.1/Bowtie2 genome alignment and Partek v6.6 mRNA annotation software. Statistical analyses were done with edgeR (Bioconductor package), excluding genes with false discovery rates >0.15, fold-change magnitudes =1.4 and log2(counts per million) =4 to avoid undefined values and the poorly defined log fold-changes for low counts close to 0. Unsupervised clustering of 441 significantly changed genes was done with dChip using rank correlation and a centroid linkage method. Scatter plots were generated in Spotfire. GSEA was performed with gene set permutation, using gene sets from MSigDB (www.broadinstitute.org/gsea/msigdb/index.jsp) or manually curated from, excluding genes without HUGO approved symbols
Publication Title
IP3 3-kinase B controls hematopoietic stem cell homeostasis and prevents lethal hematopoietic failure in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human bone marrow is a complex, diversified and well-organized hematopoietic network changing composition with age. The purpose of this study was to analyze variations in relative precursor B cell abundance in bone marrow with age by means of global gene expression profiling. RNA was isolated from composite bone marrow from 25 healthy children, adolescents and adults age 2 months to 28 years. As reference transcript for precursor B cells we used recombination activating gene RAG1 exploring the data for other transcripts showing the same profile as RAG1 with age. We identified 54 genes with correlated expression profiles to RAG1 (r 0.9, p = 0), characterized by high expression at 3 - 20 months followed by a fast decline to lower signal levels maintained until early adulthood. Immunophenotyping from a similar healthy age-matched cohort (n = 37) showed a comparable decrease of precursor B cells. Of the 54 genes 15 were characteristically B cell associated representing cell surface molecules (CD19, CD72, CD79A, CD79B, CD180, IGL@, IGLL1, VPREB1, VPREB3), a signal transduction molecule (BLNK) and transcription factors (DNTT, EBF1, PAX5, POU2AF1, RAG2). Of the remaining transcripts some may represent novel B cell transcripts or genes involved in control of B cells.
Publication Title
Striking decrease in the total precursor B-cell compartment during early childhood as evidenced by flow cytometry and gene expression changes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Estrogen plays an important role in the regulation of vascular tone and in the pathophysiology of cardiovascular disease. Physiological effects of estrogen are mediated through estrogen receptors alpha (ERalpha) and beta (ERbeta), which are both expressed in vascular smooth muscle and endothelial cells. However, the molecular pathways mediating estrogen effects in blood vessels are not well defined. We have performed gene expression profiling in the mouse aorta to identify comprehensive gene sets the expression of which is regulated by long-term (1 wk) estrogen treatment. The ER subtype dependence of the alterations in gene expression was characterized by parallel gene expression profiling experiments in ERalpha-deficient [ERalpha knockout (ERalphaKO)] and ERbeta-deficient (ERbetaKO) mice.
Publication Title
Estrogen receptors alpha and beta mediate distinct pathways of vascular gene expression, including genes involved in mitochondrial electron transport and generation of reactive oxygen species.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
KATP opposes depolarization of cells in the heart, smooth muscle, and other tissues by permitting the efflux of potassium ions and this efflux is evidently required to prevent unopposed vasoconstriction and insufficiency of coronary artery blood flow triggered by one or more cytokines induced in response to LPS. The cytokine(s) involved must elicit a dysfunctional response in the Kir6.1-deficient environment, and to gain further insight into the effects of the mutation, we examined the transcriptional status of whole heart, isolated from normal C57BL/6J mice or KcnJ8Md/Md mice, before and after injection of 1 g of LPS
Publication Title
ATP-sensitive potassium channels mediate survival during infection in mammals and insects.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A mouse model for human small cell lung carcinoma (SCLC) has been developed based on evidence in human tumors that the tumor suppressor functions of RB and p53 are defective in more than 90% of SCLC cases. We also developed another mouse model also combines loss of p130 (Rbl2), an RB-related gene, with deletion of RB and p53. These two mouse tumors were shown to closely resemble human SCLC.
Publication Title
Loss of p130 accelerates tumor development in a mouse model for human small-cell lung carcinoma.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The retinoblastoma cell cycle regulator pRb and the two related proteins p107 and p130 are thought to suppress cancer development both by inhibiting the G1/S transition of the cell cycle in response to growth-arrest signals and by promoting cellular differentiation. Here, we investigated the phenotype of Rb family triple knock-out (TKO) embryonic stem cells as they differentiate in vivo and in culture. Confirming the central role of the Rb gene family in cell cycle progression, TKO mouse embryos did not survive past mid-gestation and differentiating TKO cells displayed increased proliferation and cell death. However, patterning and cell fate determination were largely unaffected in these TKO embryos. Furthermore, a number of TKO cells, including in the neural lineage, were able to exit the cell cycle in G1 and terminally differentiate. This ability of Rb family TKO cells to undergo cell cycle arrest was associated with the repression of target genes for the E2F6 transcription factor, uncovering a pRb-independent control of the G1/S transition of the cell cycle. These results show that the Rb gene family is required for proper embryonic development but is not absolutely essential to induce G1 arrest and differentiation in certain lineages.
Publication Title
G1 arrest and differentiation can occur independently of Rb family function.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 10 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Examine global gene expression patterns in control and 35S:PAP1 Arabidopsis plants upon environmental perturbation (light and temperature) over the course of the experiments.
Publication Title
Environmental regulation of leaf colour in red 35S:PAP1 Arabidopsis thaliana.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20), Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cytomegalovirus infection drives adaptive epigenetic diversification of NK cells with altered signaling and effector function.
Sample Metadata Fields
Specimen part, Subject
View Samples