Dazl (deleted in azoospermia like) is a member of the DAZ family of germ cell-restricted RNA binding proteins required for gametogenesis from worm to human. The direct RNA targets and functions of these essential proteins are poorly understood. Here, we generated high-resolution, transcriptome-wide maps of Dazl-RNA interactions in mouse testes. These maps provide important insights into the mechanism of Dazl recruitment to mRNA and reveal Dazl binding to thousands of mRNAs predominantly through sequence-specific interactions near the polyA tail. Using transgenic mice and fluorescence activated cell sorting (FACS), we isolated DAZL knockout germ cells and used RNA-Seq to identify mRNAs sensitive to DAZL-ablation. Intersecting the RNA-Seq and Dazl-RNA interaction datasets revealed that Dazl enhances expression of a subset of directly-bound transcripts, namely mRNAs for a network of essential cell cycle regulatory genes. Collectively, our integrative analysis delineates a Dazl-dependent post-transcriptional gene regulatory program essential for mammalian germ cell maintenance. Overall design: PolyA Seq libraries generated from isolated spermatogonial cells
DAZL Regulates Germ Cell Survival through a Network of PolyA-Proximal mRNA Interactions.
Sex, Specimen part, Cell line, Subject
View SamplesA novel mouse line was found to exhibit prominent mechanosensory deficits both behaviorally and at the primary sensory afferents, and exhibits decreased ATP release from the skin.
Mechanosensory and ATP Release Deficits following Keratin14-Cre-Mediated TRPA1 Deletion Despite Absence of TRPA1 in Murine Keratinocytes.
Specimen part
View SamplesThe data contained in this record are used to differentiate between the effects of IFN-a and IFN-b on 48h cultures of the ex vivo pbmcs of ATL patients, using Affymetrix microarrays (HuGene 1.0).
IFN-β induces greater antiproliferative and proapoptotic effects and increased p53 signaling compared with IFN-α in PBMCs of Adult T-cell Leukemia/Lymphoma patients.
Specimen part, Subject
View SamplesThe epithelial-mesenchymal transition (EMT), considered essential for metastatic cancer, has been a focus of much research, but important questions remain. Here, we show that silencing or removing H2A.X, a histone H2A variant involved in cellular DNA repair and robust growth, induced mesenchymal-like characteristics including activation of EMT transcription factors, Slug and ZEB1, in HCT116 human colon cancer cells. Ectopic H2A.X re-expression partially reversed these changes; as did silencing Slug and ZEB1. In an experimental metastasis model, the HCT116 parental and H2A.X-null cells exhibited similar metastases levels, but the cells with re-expressed H2A.X exhibited substantially elevated levels. We surmise that H2A.X re-expression led to partial EMT reversal and increased robustness in the HCT116 cells, permitting them to both form tumors and to metastasize. In a human adenocarcinoma panel, H2A.X levels correlated inversely with Slug and ZEB1 levels. Together, these results point to H2A.X as a novel regulator of EMT.
The histone variant H2A.X is a regulator of the epithelial-mesenchymal transition.
Cell line
View SamplesIn addition to the recently published in situ transcriptomics of LCL skin lesions (Novais et al., Khouri et al.), we herein present the first systemic disease signature of localized cutaneous leishmaniasis (LCL), using Affymetrix microarrays (HuGene 1.0) followed by systems biology analysis of the PBMC transciptome of LCL patients (n=18), as compared to healthy controls (n=12).
Systems Approach Reveals Nuclear Factor Erythroid 2-Related Factor 2/Protein Kinase R Crosstalk in Human Cutaneous Leishmaniasis.
Specimen part, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Efficacy of the highly selective focal adhesion kinase inhibitor BI 853520 in adenocarcinoma xenograft models is linked to a mesenchymal tumor phenotype.
Cell line
View SamplesmRNA expression profiling of untreated CDX samples and correlation with sensitivity data derived from treatments with BI 853520.
Efficacy of the highly selective focal adhesion kinase inhibitor BI 853520 in adenocarcinoma xenograft models is linked to a mesenchymal tumor phenotype.
Cell line
View SamplesThe goal of this study was to analyze global gene expression in specific populations of somatosensory neurons in the periphery, including major, non-overlapping populations that include nociceptors, pruriceptors, and prorioceptors. The mammalian somatosensory nervous system encodes the perception of specific environmental stimuli. The dorsal root ganglion (DRG) contains distinct somatosensory neuron subtypes that innervate diverse peripheral tissues, mediating the detection of thermal, mechanical, proprioceptive, pruriceptive, and nociceptive stimuli. We purified discrete subtypes of mouse DRG somatosensory neurons by flow cytometry using fluorescently labeled mouse lines (SNS-Cre/TdTomato, Parv-Cre/TdTomato) in combination with Isolectin B4-FITC surface staining (IB4). This allowed identification of transcriptional differences between these major populations, revealing enrichment of voltage-gated ion channels, TRP channels, G-protein coupled receptors, transcription factors, and other functionally important classes of genes within specific somatosensory neuron subsets.
Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression.
Cell line
View SamplesThe transcriptional repressor ZBTB18 was overexpressed in the brain tumor xenoline JX6 by lentiviral transduction. Three independent transduction were performed (biological replicates) and analyzed by gene expression aray. Gene set enrichemnt analysis (GSEA) showed changes in the expression of mesenchymal signature. A subset of genes was further valiadted by qPCR. These results indicate a role of ZBTB18 as repressor of mesenchymal genes in Glioblastoma.
Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression.
Cell line
View Samples