Gene regulation at the maternal-embryonic transition in the pre-implantation mouse embryo is not well understood. We knock down Ccna2 to establish proof-of-concept that antisense morpholino oligonucleotides can be used to target specific genes. We applied this strategy to study Oct4 and discovered that Oct4 is required prior to blastocyst development. Specifically, gene expression is altered as early as the 2-cell stage in Oct4-knockdown embryos.
A novel and critical role for Oct4 as a regulator of the maternal-embryonic transition.
No sample metadata fields
View SamplesLandmark events occur in a coordinated manner during preimplantation development of the mammalian embryo, yet the regulatory network that orchestrates these events remains largely unknown.
An Oct4-Sall4-Nanog network controls developmental progression in the pre-implantation mouse embryo.
No sample metadata fields
View SamplesThe impact of specific p53 mutations on ovarian tumor development and response to therapeutic treatment remain limited. Here, using transgenic mouse models of epithelial ovarian cancer (EOC), we demonstrated that the Trp53R172H mutation promotes EOC progression compared to wild-type p53, but with different consequences between heterozygous and homozygous mutation status. EOC expressing heterozygous Trp53R172H mutation has enhanced responsiveness to steroid hormones and at late stage developed mucinous cystadenocarcinoma. These findings open new realms for exploring the interaction between p53 and steroid receptor, and the allelic status of p53 in EOC development and treatment.
Mutant p53 Promotes Epithelial Ovarian Cancer by Regulating Tumor Differentiation, Metastasis, and Responsiveness to Steroid Hormones.
Age, Specimen part
View SamplesWe tested the hypothesis that a set of differentially expressed genes could be used to predict cardiovascular phenotype in mice after prolonged catecholamine stress.
Gene expression profiling: classification of mice with left ventricle systolic dysfunction using microarray analysis.
No sample metadata fields
View SamplesDuring mammalian kidney development, mesenchymal nephron progenitors (cap mesenchyme) differentiate into the epithelial cells that go on to form the nephron. Although differentiation of nephron progenitors is triggered by activation of Wnt/b-catenin signaling, constitutive activation of Wnt/b-catenin signaling blocks epithelialization of nephron progenitors. Full epithelialization of nephron progenitors requires transient activation of Wnt/b-catenin signaling. We performed transcriptional profiling of nephron progenitors responding to constitutive or transient activation of Wnt/b-catenin signaling.
Six2 and Wnt regulate self-renewal and commitment of nephron progenitors through shared gene regulatory networks.
No sample metadata fields
View SamplesNuocytes are a recently described cell that responds to both IL-25 and IL-33 and produce high levels of IL-13 and IL-5
Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity.
Specimen part, Time
View SamplesHypertrophic scar (HTS) formation is characterized by exuberant fibroproliferation for reasons that remain poorly understood1. One important but often overlooked component of wound repair is mechanical force, which regulates reciprocal cell-matrix interactions through focal adhesion components including focal adhesion kinase (FAK)1,2. Here we report that FAK is activated following cutaneous injury and that this activation is potentiated by mechanical loading. Transgenic mice lacking fibroblast-specific FAK exhibit significantly less fibrosis in a preclinical model of HTS formation. Inflammatory pathways involving monocyte chemoattractant protein-1 (MCP-1), a chemokine highly implicated in human skin fibrosis3, are triggered following FAK activation, mechanistically linking physical force to fibrosis. Further, small molecule inhibition of FAK effectively abrogates fibroproliferative mechanisms in human cells and significantly reduces scar formation in vivo. Collectively, these findings establish a molecular basis for HTS formation based on the mechanical activation of fibroblast-specific FAK and demonstrate the therapeutic potential of targeted mechanomodulatory strategies.
Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling.
Sex, Specimen part
View SamplesActivated phosphoinositide 3-kinase (PI3K)-AKT signaling appears to be an obligate event in the development of cancer. The highly related members of the mammalian FoxO transcription factor family, FoxO1, FoxO3, and FoxO4, represent one of several effector arms of PI3K-AKT signaling, prompting genetic analysis of the role of FoxOs in the neoplastic phenotypes linked to PI3K-AKT activation. While germline or somatic deletion of up to five FoxO alleles produced remarkably modest neoplastic phenotypes, broad somatic deletion of all FoxOs engendered a progressive cancer-prone condition characterized by thymic lymphomas and hemangiomas, demonstrating that the mammalian FoxOs are indeed bona fide tumor suppressors. Transcriptome and promoter analyses of differentially affected endothelium identified direct FoxO targets and revealed that FoxO regulation of these targets in vivo is highly context-specific, even in the same cell type. Functional studies validated Sprouty2 and PBX1, among others, as FoxO-regulated mediators of endothelial cell morphogenesis and vascular homeostasis.
FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Neural-specific Sox2 input and differential Gli-binding affinity provide context and positional information in Shh-directed neural patterning.
Specimen part, Treatment
View SamplesThe objective of this study was to identify genes regulated by Sonic Hedgehog pathway stimulation in neural progenitors.
Neural-specific Sox2 input and differential Gli-binding affinity provide context and positional information in Shh-directed neural patterning.
Specimen part, Treatment
View Samples