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GSE47577
Homo sapiens
33 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Uterine NK cells (uNK) play a role in the regulation of placentation but their functions in non-pregnant endometrium are not understood. We have previously reported suppression of endometrial bleeding and alteration of spiral artery morphology in women exposed to asoprisnil, a progesterone receptor modulator (PRM). We now compare global endometrial gene expression in asoprisnil-treated versus control women and demonstrate a statistically significant reduction of genes in the IL-15 pathway, known to play a key role in uNK development and function. Suppression of IL-15 by asoprisnil was also observed at mRNA level (p<0.05), and immunostaining for NK cell marker CD56 revealed a striking reduction of uNK in asoprisnil-treated endometrium (p<0.001). IL-15 levels in normal endometrium are progesterone-responsive. Progesterone receptor (PR) positive stromal cells transcribe both IL-15 and IL-15RA. Thus, the response of stromal cells to progesterone will be to increase IL-15 trans-presentation to uNK, supporting their expansion and differentiation. In asoprisnil-treated endometrium, there is a marked down-regulation of stromal PR expression and virtual absence of uNK. These novel findings indicate that the IL-15 pathway provides a missing link in the complex interplay between endometrial stromal cells, uNK and spiral arteries affecting physiological and pathological endometrial bleeding.
Publication Title
Uterine NK cells regulate endometrial bleeding in women and are suppressed by the progesterone receptor modulator asoprisnil.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Purpose: Epidemiological and intervention studies have attempted to link the health effects of a diet rich in fruits and vegetables with the consumption of polyphenols and their impact in neurodegenerative diseases. Studies have shown that polyphenols can cross the intestinal barrier and reach concentrations in the bloodstream able to exert effects in vivo. However, the effective uptake of polyphenols in the brain is still regarded with some reservations. Here we describe a combination of approaches to examine the putative transport of blackberry-digested polyphenols (BDP) across the blood-brain barrier (BBB) and ultimate evaluation of their beneficial effects.
Publication Title
Blood-brain barrier transport and neuroprotective potential of blackberry-digested polyphenols: an in vitro study.
Sample Metadata Fields
Sex, Specimen part, Cell line, Race
View Samples- Mus musculus
- 16 Downloadable Samples
Illumina HiSeq 4000
Description
The overall goal of this study was to clarify the role of MeCP2 in adult cognition. As one of the measures we analyzed gene expression changes associated with MeCP2 loss in the adult hippocampus. The analysis was performed in basal conditions and after exposure to a novel environment. We report gene expression data of mouse adult hippocampal tissue in which MeCP2 has been knockeddown in both conditions. Overall design: Hippocampal mRNA profiles of 3 months old mice after delivery of a control shRNA sequence or a MeCP2-specific shRNA sequence by RNA-seq. Profiles in basal conditions and after (30 minutes) exposure to a novel environment were obtained. Each condition is in quadriplicate.
Publication Title
Adult hippocampal MeCP2 preserves the genomic responsiveness to learning required for long-term memory formation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Cell fate perturbations underlie many human diseases, including breast cancer. However, the regulation of breast cell fate remains largely elusive. The mammary gland epithelium consists of differentiated luminal epithelial and basal myoepithelial cells, as well as undifferentiated stem cells and more restricted progenitors. Breast cancer originates from this epithelium but the molecular mechanisms underlying breast epithelial hierarchy remain ill-defined. Mouse and human luminal cells express keratins (K)18, 8, 19 and/or estrogen receptor (ER) and progesterone receptor (PR), their basal counterparts express K5, 14 and/or p63 and/or -smooth-muscle actin (-SMA)4-6. In this study, using a high-content confocal image-based shRNA screen for tumor suppressors regulating human breast cell fate, we discovered that ablation of the Hippo kinases large tumor suppressor (LATS) 1 and 2, promoted luminal fate and increased the number of bipotent and luminal progenitors, the proposed cell-of-origin of most human breast cancers. Mechanistically, we discovered a crosstalk between Hippo and ER signaling. In the presence of LATS, ER was targeted for ubiquitination and proteasomal degradation. Loss of LATS stabilized ER and Hippo effectors YAP/TAZ, which in concert control breast cell fate via intrinsic and paracrine mechanisms. Our findings uncover a novel non-canonical (i.e., YAP/TAZ-independent) effect of LATS in the regulation of human breast cell fate.
Publication Title
The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk with ERα.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Perturbation of the tightly regulated dynamic process of cell fate underlies many human diseases. The molecular mechanisms regulating breast cell fate in the hierarchically organized luminal and basal lineages of breast epithelium remain largely elusive. We performed a high-content confocal image-based shRNA screen for regulators of primary human breast cell fate. Inhibition of the Hippo kinases LATS was found to promote luminal fate and increase the number of progenitors, which is a paradox given that Hippo effectors YAP/TAZ have been associated with basal fate. Mechanistically, LATS loss increases the activities of YAP/TAZ and ER, which in concert control breast cell fate via intrinsic and paracrine effects. Reduced LATS expression is found in breast cancers with a poor prognosis; this diminishes the sensitivity of ER-positive- and increases the sensitivity of ER-negative cancers to endocrine therapy. Thus, in this study we have unraveled crosstalk between Hippo and estrogen signaling and shown that LATS loss triggers expansion of luminal progenitors, the highly suspected cell-of-origin in most breast cancers.
Publication Title
The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk with ERα.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 49 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
PIK3CA(H1047R) induces multipotency and multi-lineage mammary tumours.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 34 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This study examined the effect of early pregnancy on the gene expression profiles of stromal and various epithelial mammary cell subpopulations in mice.
Publication Title
PIK3CA(H1047R) induces multipotency and multi-lineage mammary tumours.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: We report the detailed development of biomarkers to predict the clinical outcome under dengue infection. Transcriptional signatures from purified peripheral blood mononuclear cells were derived from whole-genome gene-expression microarray data and validated by quantitative PCR and tested in independent samples. Methodology/Principal Findings: The study was performed on patients of a well-characterized dengue cohort from Recife, Brazil. The samples analyzed were collected prospectively from acute febrile dengue patients who evolved with different degrees of disease severity, classic dengue fever or dengue hemorrhagic fever (DHF) and compared with similar samples from other non-dengue febrile illnesses. The DHF samples were collected 2-3 days before the presentation of the plasma leakage symptoms. Differentially-expressed genes were selected by univariate statistical tests as well as multivariate classification techniques. The results showed that at early stages of dengue infection, the genes involved in effector mechanisms of innate immune response presented a weaker activation on patients who later developed hemorrhagic fever, whereas the genes involved in apoptosis were expressed in higher levels. Conclusions/Significance: Some of the gene expression signatures displayed estimated accuracy rates of more than 95%, indicating that expression profiling with these signatures may provide a useful means of DHF prognosis at early stages of infection
Publication Title
Gene expression profiling during early acute febrile stage of dengue infection can predict the disease outcome.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 25 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This study examined the gene expression profile of mammary tumors derived from Lgr5- and K8-positive cell-of-origins
Publication Title
PIK3CA(H1047R) induces multipotency and multi-lineage mammary tumours.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This study examined the effect of mutant PIK3CAH1047R expression in mammary subsets of preneoplastic mammary glands from Lgr5-creERT2/PIK3CA H1047R mice
Publication Title
PIK3CA(H1047R) induces multipotency and multi-lineage mammary tumours.
Sample Metadata Fields
Specimen part, Treatment
View Samples