We have demonstrated previously that mammalian sexual differentiation requires both GATA4 and FOG2 transcription regulators to assemble the functioning testis. We have now determined that the sexual development of female mice is profoundly affected by the loss of GATA4-FOG2 interaction. We have also identified the Dkk1 gene, encoding a secreted inhibitor of canonical -catenin signaling as a target of GATA4/FOG2 repression in the developing ovary. The tissue-specific ablation of the -catenin gene in the gonads disrupts female development while in the Gata4ki/ki/Dkk1-/- or Fog2-/-/Dkk1-/- embryos the normal ovarian gene expression pattern is partially restored. Control of ovarian development by the GATA4/FOG2 complex presents a novel insight into the crosstalk of transcriptional regulation and extracellular signaling in ovarian development.
Ovarian development in mice requires the GATA4-FOG2 transcription complex.
Specimen part
View SamplesLongitudinal bone growth depends upon the execution of an intricate series of cellular activities by epiphyseal growth plate chondrocytes. In order to better understand these coordinated events, microarray analysis was used to compare gene expression in chondrocytes isolated from the proliferative and hypertrophic zones of the avian growth plate.
Use of microarray analysis to study gene expression in the avian epiphyseal growth plate.
Age, Specimen part
View SamplesComparison of genome-wide mRNA expresson between tumor-infiltrating CD8+ T cells from the tumor (hypofunctional T cells) and periphery (functional T cells)
Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model.
Specimen part
View SamplesGene expression profile of laser-capture microdissected epithelium component of 6 mucinous cystic neoplasms of the pancreas were included in the study. The expression arrays were generated with Affymetrix HU133A gene chips (18,462 genes/EST transcripts).
Characterization of gene expression in mucinous cystic neoplasms of the pancreas using oligonucleotide microarrays.
Sex, Specimen part, Disease, Subject
View SamplesGrowth and patterning of the face relies on several small buds of tissue, the facial prominences, which surround the primitive mouth. Beginning around E10 of mouse development the prominences undergo rapid growth and morphogenesis. By E11.5 the medial nasal prominences are in close apposition in the midline, as are the maxillary and medial nasal prominences on either side of the developing face. Subsequently, by E12.5 the nasal and maxillary prominences fuse to form a continuous shelf at the front of the face - the primary palate. Individual prominences are associated with specific developmental processes, and this is reflected by patterns of differential gene expression that give the prominences their unique identities. Thus, only the mandibular and maxillary prominences give rise to dentition while the frontonasal prominence has a unique role in olfaction, and the mandibular prominence in taste. We used microarrays to detail the differential gene expression program in each of the mandibular, maxillary, and frontonasal prominences during the key developmental timepoints of E10.0 through E12.5.
Spatial and temporal analysis of gene expression during growth and fusion of the mouse facial prominences.
Specimen part
View SamplesWe previously found that the SF3A mRNA splicing complex was required for a robust innate immune response; SF3A acts in part by inhibiting the production of a negatively acting splice form of the TLR signaling adaptor MyD88. Here we inhibit SF3A1 using RNAi and subsequently perform an RNAseq study to identify the full complement of genes and splicing events regulated by SF3A in murine macrophages. Surprisingly, SF3A has substantial specificity for mRNA splicing events in innate immune signaling pathways compared to other pathways, affecting the splicing of many genes in the TLR signaling pathway to modulate the innate immune response. Overall design: RNAseq was used to monitor the effects of SF3A1 siRNA-mediated knockdown in murine macrophages. Three biological replicates were used for each of the four treatment combinations (with/without siRNA, with/without LPS). The first replicates for each combination were each sequenced in two runs, which were combined in the analysis.
Regulation of toll-like receptor signaling by the SF3a mRNA splicing complex.
No sample metadata fields
View SamplesThis investigation provides a robust multi-dimensional compendium of gene expression data relevant to mouse facial development. It profiles the transcriptome ofectoderm and mesenchyme from the three facial prominences in a time series encompassing their growth and fusion. Analysis of the dataset identified more than 8000 differentially expressed genes comprising dramatically different ectoderm and mesenchyme programs. The mesenchyme programs included many genes identified in earlier analyses as well hundreds of genes not previously implicated in craniofacial development. The ectoderm programs included over a thousand genes that highlight epithelial structure, cell-cell interactions and signaling.
Systems biology of facial development: contributions of ectoderm and mesenchyme.
Specimen part
View SamplesIdentifying the effect of the co-regulator Hic-5 (TGFB1I1) and TGFB on the transcriptional profile of WPMY human prostate fibroblast cells with view to further elucidating the broader biological role of Hic-5 and TGFB on fibroblast.
VDR activity is differentially affected by Hic-5 in prostate cancer and stromal cells.
Specimen part, Cell line, Treatment
View Samplesbeta-catenin is an essential mediator of canonical Wnt signaling and a central component of the cadherin-catenin epithelial adhesion complex. Dysregulation of beta-catenin expression has been described in pancreatic neoplasia. Newly published studies have suggested that beta-catenin is critical for normal pancreatic development although these reports reached somewhat different conclusions. In addition, the molecular mechanisms by which loss of beta-catenin affects pancreas development are not well understood. The goals of this study then were; 1] to further investigate the role of beta-catenin in pancreatic development using a conditional knockout approach and 2] to identify possible mechanisms by which loss of beta-catenin disrupts pancreatic development. A Pdx1-cre mouse line was used to delete a floxed beta-catenin allele specifically in the developing pancreas, and embryonic pancreata were studied by immunohistochemistry and microarray analysis.
Wnt/beta-catenin signaling is required for development of the exocrine pancreas.
No sample metadata fields
View SamplesChronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality, is primarily caused by prolonged exposures to cigarette smoke (CS) and the disease may persist or progress even after smoking cessation. To provide novel insight the mechanisms of COPD development we investigated temporal patterns of lung transcriptome expression in response to chronic CS exposure that also persist following CS cessation, using next generation sequencing techniques. Whole lung RNA-seq data was analyzed from C57Bl/6 mice exposed to CS for 1 day, 7 days, 1 month, 3 months, 6 months, and 9 months as well as for 6 months followed by 3 months of cessation. Age-matched littermate mice exposed to ambient air were used as control (AC). Differential gene expression and pathway analyses revealed consistent upregulation of genes involved in glutathione metabolism, a pathway previously implicated in lung responses to chronic CS and in COPD, that was reversible upon cessation. In addition, novel patterns in mouse-model pathways such as pyrimidine metabolism and phosphatidylinositol signaling system and have been recognized. Genes in these pathways encoding for enzymes controlling metabolic functions were significantly altered by CS exposures and were associated with congruent abnormalities in contemporaneous plasma metabolomic profiles. The bioinformatics integration of lung tissue genomics and plasma metabolomics uncovered that changes in lung gene expression induced by CS exposures are translated in systemic metabolic signatures, with potential implication in the development of COPD. Overall design: Whole transcriptome profiling of air control vs cigarette smoke-exposed mice at each of 6 timepoints from 1 day to 9 months of exposure, including a stop smoking group exposed to 6 months of CS followed by 3 months of ambient air recovery. Each treatment-by-time experimental group contains 5 biological replicates. 3 samples were discarded for quality reasons.
Gene and metabolite time-course response to cigarette smoking in mouse lung and plasma.
Specimen part, Cell line, Treatment, Subject, Time
View Samples