Glioblastoma multiforme is the most common and most aggressive type of primary brain tumor. The brain-infiltrative character of glioblastoma makes complete surgical removal of the tumor impossible and neither radiation nor current chemotherapy provide cure. Recent evidence shows that glioblastoma multiforme consists of heterogeneous cell populations which differ in tumor-forming potential. Enriched tumor-initiating capacity has been linked to poorly differentiated glioblastoma cells sharing features with neural stem cells. Thus, these cells are important targets for new therapeutic strategies.
An RNAi screen identifies TRRAP as a regulator of brain tumor-initiating cell differentiation.
Cell line
View SamplesCell 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.
The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk with ERα.
Specimen part, Cell line
View SamplesPerturbation 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.
The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk with ERα.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Histone Methyltransferase G9a Is Required for Cardiomyocyte Homeostasis and Hypertrophy.
Treatment
View SamplesThe role of the histone mehyltrasferase G9a (also known as Ehmt2) in cardiac hypertrophy has not been studied extensively. To address how G9a promotes cardiac hypertrophy, we assessed the gene expression signature defined by G9a in cardiomyocytes (CM) of mice subject to transverse aortic constriction (TAC) for 1 wk, a surgical procedure that causes cardiac hypertrophy following the induction of pressure overload. To this end, we compared the expression profiles of CMs isolated from mice treated with the G9a inhibitor BIX-01294 and control groups (untreated and DMSO-treated mice at baseline and after TAC). The expression profiles were defined by Illumina arrays .
Histone Methyltransferase G9a Is Required for Cardiomyocyte Homeostasis and Hypertrophy.
No sample metadata fields
View SamplesThe role of the histone mehyltrasferase G9a (also known as Ehmt2) in heart has not been extensively studied. To identify the genes regulated by G9a in the normal heart, we first generated a conditional, cardiac-specific KO mouse for this gene using the Cre-Lox approach, crossing G9a flox/flox mice with aMHC-MerCreMer mice (Cre mice were used as controls). Then, we sequenced total RNA (Total-RNA-seq) from cardiomyocyte-enriched populations isolated from G9a-KO and Cre mice, and compared the two expression profiles. Overall design: Profiling of the transcriptome of cardiomyocyte-enriched populations isolated from G9a-KO and Cre mice. Two biological replicates were profiled for each cell type.
Histone Methyltransferase G9a Is Required for Cardiomyocyte Homeostasis and Hypertrophy.
Cell line, Subject
View SamplesThe experiment describes the transcriptional response of Saccharomyces cerevisiae BY4741 and of the deletion mutant Δhaa1 following an incubation in the presence of 50 mM acetic acid (at pH 4.0)
Genomic expression program involving the Haa1p-regulon in Saccharomyces cerevisiae response to acetic acid.
Compound
View SamplesTo try to identify the mechanism of STAT3s indirect action we have used a genomic approach to map the binding sites of STAT3 within the genome and also used RNA-seq technology to map the changes in RNA expression and transcript isoform abundance in response to IL-10. Overall design: Examination of transcriptome changes in peritoneal macrophages when treated with IL-10 for 4 hours. RNA was extracted and sequenced.
Genome-wide analysis of STAT3 binding in vivo predicts effectors of the anti-inflammatory response in macrophages.
Sex, Specimen part, Cell line, Subject
View SamplesRNA-seq was used to look at the transcriptome changes and the early events of T cell receptor stimulation in CD4+ T cells Overall design: CD4+ T cells were stimulated with immobilised anti-CD3/CD28 antibodies for 4 hours and RNA was extracted and subjected to RNA-seq analysis.
Discovery and characterization of new transcripts from RNA-seq data in mouse CD4(+) T cells.
Sex, Specimen part, Cell line, Treatment, Subject
View SamplesNatural grape-juice fermentations involve the sequential development of different yeast species which strongly influence the chemical and sensorial traits of the final product. In the present study,we aimed to examine the transcriptomic response of Saccharomyces cerevisiae to the presence of Hanseniaspora guilliermondii wine fermentation.
Genomic expression program of Saccharomyces cerevisiae along a mixed-culture wine fermentation with Hanseniaspora guilliermondii.
Treatment, Time
View Samples