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GSE21947
Homo sapiens
29 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Background: We hypothesize that important genomic differences between breast cancer subtypes occur early in carcinogenesis. Therefore, gene expression might distinguish histologically normal breast epithelium (NlEpi) from breasts containing estrogen receptor positive (ER+) compared with estrogen receptor negative (ER-) cancers.
Publication Title
Gene expression profiles of estrogen receptor-positive and estrogen receptor-negative breast cancers are detectable in histologically normal breast epithelium.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Expression of microRNA and their gene targets are dysregulated in preinvasive breast cancer.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Introduction: microRNAs (miRNAs) are short non-coding RNAs that negatively regulate gene expression and may play a causal role in invasive breast cancer. Since many genetic aberrations of invasive disease are detectable in earlier stages, we hypothesized that miRNA expression dysregulation and the predicted changes in gene expression would also be found in early breast neoplasias. Methods: Expression profiling of 365 miRNAs by RT-qPCR was combined with laser-capture microdissection to obtain an epithelial specific miRNA expression signature of normal breast epithelium (n=9) and of paired samples of histologically normal epithelium (HN) and ductal carcinoma in situ (DCIS) (n=16). To determine how miRNAs may control the expression of co-dysregulated mRNAs we also performed gene expression microarray analysis in the same paired HN and DCIS samples and integrated this with miRNA-target prediction. We further validated several target pairs by modulating the expression levels of miRNAs in MCF7 cells and measured the expression of target mRNAs and proteins. Results: Thirty-five miRNAs were aberrantly expressed between RM, HN and DCIS. Twenty-nine miRNAs and 420 mRNAs were aberrantly expressed between HN and DCIS. Combining these two datasets with miRNA-target prediction we identified two established target pairs (miR-195:CCND1 and miR-21:NFIB) and tested several novel miRNA:mRNA target pairs. Over-expression of the putative tumor-suppressor miR-125b, under-expressed in DCIS, repressed the expression of MEMO1, which is required for ErbB2-driven cell motility (also a target of miR-125b); and NRIP1/RIP140, which modulates the transcriptional activity of the estrogen receptor. Knockdown of the putative oncogenic miRNAs miR-182 and miR-183, both highly over-expressed in DCIS, increased the expression of CBX7 (which regulates E-cadherin expression), DOK4, NMT2, and EGR1. Augmentation of CBX7 by knockdown of miR-182 expression, in turn, positively regulated the expression of E-cadherin, a key protein involved in maintaining normal epithelial cell morphology which is commonly lost during neoplastic progression. Conclusions: These data provide the first miRNA expression profile of normal breast epithelium and of pre-invasive breast carcinoma. Further, we demonstrate that altered miRNA expression can modulate gene expression changes that characterize these early cancers. We conclude that miRNA dysregulation likely plays a substantial role in early breast cancer development.
Publication Title
Expression of microRNA and their gene targets are dysregulated in preinvasive breast cancer.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Insight into the role of Insulin-like Growth Factor (IGF) in development of lungs has come from the study of genetically modified mice. IGF1 is a key factor during lung development. IGF1 deficiency in the neonatal mouse causes respiratory failure collapsed alveoli and altered alveolar septa. To further characterize IGF1 function during lung development we analyzed Igf1-/- mouse prenatal lungs in a C57Bl/6 genetic background. Mutant lungs showed disproportional hypoplasia, disorganized extracellular matrix and dilated alveolar capillaries. IGF1 target genes during lung maturation were identified by analyzing RNA differential expression in Igf1-/- lungs using microarrays.
Publication Title
Transcriptome analysis in prenatal IGF1-deficient mice identifies molecular pathways and target genes involved in distal lung differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene expression in histologically normal epithelium from breast cancer patients and cancer-free prophylactic mastectomy patients share a similar profile
Publication Title
Gene expression in histologically normal epithelium from breast cancer patients and from cancer-free prophylactic mastectomy patients shares a similar profile.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 6 Downloadable Samples
NextSeq 500
Description
Previous studies have reported that microglia depletion leads to impairment of synapse formation and these cells rapidly repopulate from CNS progenitors. However, the impact of microglia depletion and repopulation on the long-term state of the CNS environment has not been characterized. Here, we found by RNA-seq analysis that acute and synchronous microglia depletion results in a type 1-interferon inflammatory signature in degenerating somatosensory cortex in microglia-depleted mice. Transcriptomic and mass cytometry analysis of repopulated microglia demonstrates an interferon regulatory factor 7-driven activation state. Minocycline and anti-IFNAR1 antibody treatment attenuate the CNS type-1 interferon-driven inflammation and restore microglia homeostasis. Together, we found that acute microglia ablation induces a type-1 interferon activation state of grey matter microglia associated with acute neurodegeneration. Overall design: RNAseq analysis of brain cortical tissue from control and microglia-depleted mice.
Publication Title
Acute microglia ablation induces neurodegeneration in the somatosensory system.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 60 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Peripheral whole blood transcriptome profiles of pregnant women enrolled in the Vitamin D Antenatal Asthma Reduction Trial (VDAART) at enrollment during early pregnancy, and again at 32-38 weeks of gestation. Mothers were enrolled in 2 treatment groups: Intervention group with 4400 IU vitamin D supplementation and Control group with 400 IU vitamin D supplementation.
Publication Title
The Role of Vitamin D in the Transcriptional Program of Human Pregnancy.
Sample Metadata Fields
Sex, Specimen part, Treatment, Race
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
We identified the ubiquitin ligase Huwe1 as a crucial regulator of hematopoietic stem cell (HSC) functions. We generated Huwe1 conditional knock-out mice and discovered that the loss of this ligase causes an increased proliferation and stem cell exhaustion, together with a decreased lymphoid specification in vivo. We observed that the ubiquitin ligase Huwe1 is controlling the expression of N-myc at the level of the most immature stem and progenitor hematopoietic populations, mediating the described effects. Overall design: High-troughput RNA-sequencing of sorted HSC (Lin-Sca+Kit+CD48-CD150+) from wild type or Huwe1 conditional knockout mice (constitutively deleted with Vav-Cre recombinase or inducibly deleted with Mx1-Cre)
Publication Title
The ubiquitin ligase Huwe1 regulates the maintenance and lymphoid commitment of hematopoietic stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We identified the ubiquitin ligase Huwe1 as a crucial regulator of hematopoietic stem cell (HSC) functions. We generated Huwe1 conditional knock-out mice and discovered that the loss of this ligase causes an increased proliferation and stem cell exhaustion, together with a decreased lymphoid specification in vivo. We observed that the ubiquitin ligase Huwe1 is controlling the expression of N-myc at the level of the most immature stem and progenitor hematopoietic populations, mediating the described effects.
Publication Title
The ubiquitin ligase Huwe1 regulates the maintenance and lymphoid commitment of hematopoietic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
The quality of maternal care in early-life plays a crucial role in mammalian neurodevelopment. Augmented maternal care (AMC) is a well-established rodent model of enhanced neonatal care. Rats that have undergone AMC have improved stress resilience and cognition compared with rats that have experienced normal levels of maternal care or adverse neonatal stress. However, the epigenomic basis of long-lived responses to AMC has not been previously explored. Thus, we employed whole-genome bisulfite sequencing (WGBS), RNA-sequencing (RNA-seq), and a multiplex microRNA (miRNA) assay to assess DNA cytosine methylation, gene expression, and miRNA expression, respectively. The integrated results identify a suite of 20 prioritized candidates impacted by AMC. Overall, these results identified AMC-induced regulatory differences in genes related to neurotransmission, neurodevelopment, protein synthesis, and oxidative phosphorylation in addition to the expected stress response genes. Together, these unbiased results represent a key progression in understanding the complex mechanisms underlying the early-life mechanisms for AMC programming stress resiliency. Overall design: DNA methylation and RNA were assayed in augmented maternal care male rats as well as controls.
Publication Title
Experience-dependent neuroplasticity of the developing hypothalamus: integrative epigenomic approaches.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples