PURPOSE: To examine if a parental high fat diet (HFD) influences metabolic health in two generations of offspring, and alters the germ cell (GC) transcriptome. PROCEDURE: GC-eGFP Sprague Dawley rats were weaned onto HFD (45% fat) or Control Diet (CD; 10% fat). After metabolic testing, founders (F0) were bred with controls, establishing the F1 generation. Germ cells from F0 males were isolated and their RNA sequenced. F1 rats were bred with control rats at 17 weeks to generate F2 offspring. FINDINGS: HFD resulted in 9.7% and 14.7% increased weight in male and female F0 respectively. F1 offspring of HFD mothers were heavier than controls. F1 daughters of HFD-fed males were also heavier. F2 male offspring derived from HFD-fed maternal grandfathers were 7.2% heavier, and exhibited increases of 31% in adiposity, 97% in plasma leptin and 300% in luteinising hormone to testosterone ratio. HFD exposure did not alter the F0 GC transcriptome. CONTROLS: Matched CD was consumed by all animals not consuming the HFD. Animals were compared to a parallel cohort of CD rats. CONCLUSIONS: HFD consumption by maternal grandfathers results in a disrupted metabolic phenotype in grandsons. This effect is not mediated by alterations to the GC transcriptome. Overall design: Male rats high fat diet vs. control diet. 4 replicates per condition. SmallRNA seq and mRNAseq for each replicate and condition
High-fat diet disrupts metabolism in two generations of rats in a parent-of-origin specific manner.
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View SamplesWe tested the effect iof Pbcas4 knockdown using a specific shRNA on the expression of genes sharing miRNA binding sites in mouse N2A cells.
Evidence for conserved post-transcriptional roles of unitary pseudogenes and for frequent bifunctionality of mRNAs.
Cell line, Treatment
View SamplesHypothalamic hamartomas (HHs) are congenital lesions of the neuroendocrine brain composed of neurons and astroglia. Frequently, HHs are associated with central precocious puberty (CPP) and/or gelastic seizures. Because HHs might express genes similar to those required for the initiation of normal puberty we used cDNA arrays to compare the gene expression profile of a HH associated with CPP with three HHs not accompanied by sexual precocity. Our aim was to identify genes whose expression may be selectively altered in the HH with CPP and hence, involved in the onset of puberty.
Gene expression profiling of hypothalamic hamartomas: a search for genes associated with central precocious puberty.
No sample metadata fields
View SamplesThis study set out to assay the (polyA+) transcriptomes of single mature (MHCII high) mouse medullary thymic epithelial cells (mTEC). Overall design: Following isolation by FACs, the transcriptomes of single mature mTEC was assayed using the Fluidigm C1 microfluidics platform and Illumina RNA-seq.
Population and single-cell genomics reveal the Aire dependency, relief from Polycomb silencing, and distribution of self-antigen expression in thymic epithelia.
No sample metadata fields
View SamplesThis study set out to assay the (polyA+) transcriptomes of specific FACS sorted populations of mouse thymic epithelial cells (TEC). Overall design: Two biological replicates of each of seven murine TEC populations were FACS sorted and sequenced.
Population and single-cell genomics reveal the Aire dependency, relief from Polycomb silencing, and distribution of self-antigen expression in thymic epithelia.
No sample metadata fields
View SamplesEarly chemotherapy for advanced/metastatic non-castration resistant prostate cancer (PCa) may improve overall patient survival. We studied the safety, tolerability and early efficacy of up-front docetaxel chemotherapy and androgen deprivation therapy (ADT) versus ADT alone for patients with newly-diagnosed advanced/metastatic PCa. As proof of concept, we undertook in vivo gene expression profiling by next generation RNA sequencing (RNA-Seq). Overall design: Tumour biposies from 6 patients were taken before and after treatment with combined ADT and docetaxcel for 6 weeks
Identification of a candidate prognostic gene signature by transcriptome analysis of matched pre- and post-treatment prostatic biopsies from patients with advanced prostate cancer.
Specimen part, Subject, Time
View SamplesAndrogen ablation therapy (AAT) is standard treatment for locally-advanced/metastatic prostate cancer (PCa). Many patients develop castration-resistance (CRPCa) after ~2-3 years, with a poor prognosis. The molecular mechanisms underlying CRPCa progression are unclear. mRNA-Seq was performed on tumours from 7 patients with locally-advanced/metastatic PCa before and ~22 weeks after AAT initiation. Differentially regulated genes were identified in treatment pairs. Overall design: Tumour biopsies from 7 patients were taken before and after AAT treatment
Next-generation sequencing of advanced prostate cancer treated with androgen-deprivation therapy.
Specimen part, Subject, Time
View SamplesThe search for developmental mechanisms driving vertebrate organogenesis has paved the way toward a deeper understanding of birth defects. During embryogenesis, parts of the heart and craniofacial muscles arise from pharyngeal mesoderm (PM) progenitors. Here, we reveal a hierarchical regulatory network of a set of transcription factors expressed in the PM that initiates heart and craniofacial organogenesis. Genetic perturbation of this network in mice resulted in heart and craniofacial muscle defects, revealing robust cross-regulation between its members. We identified Lhx2 as a novel player during cardiac and pharyngeal muscle development. Lhx2 and Tcf21 genetically interact with Tbx1, the major determinant in the etiology of DiGeorge/velo-cardio-facial/22q11.2 deletion syndrome. Furthermore, knockout of these genes in the mouse recapitulates specific cardiac features of this syndrome. We suggest that PM-derived cardiogenesis and myogenesis are network properties rather than properties specific to individual PM members. These findings shed new light on the developmental underpinnings of congenital defects.
Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution.
Cell line, Time
View SamplesGenome-wide expression analysis of hapmap lymphoblastoid and ENCODE project cell lines stimulated with calcitriol
A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution.
Cell line, Time
View Samples