ATC are among the most lethal malignancies, for which there is no effective treatment.
Cell cycle deregulation and TP53 and RAS mutations are major events in poorly differentiated and undifferentiated thyroid carcinomas.
Sex, Specimen part
View SamplesNo description.
Mili and Miwi target RNA repertoire reveals piRNA biogenesis and function of Miwi in spermiogenesis.
Cell line, Subject
View SamplesTo define and compare the genome-wide transcriptional signatures of Notch1+ cells in intestinal tumors and in normal ISCs we performed Affymetrix analyses of these two populations.
Lineage tracing of Notch1-expressing cells in intestinal tumours reveals a distinct population of cancer stem cells.
Specimen part
View SamplesIntravenous Immunoglobulin (IVIg) is widely used as an immunomodulatory therapy. We have recently demonstrated that IVIg protects against airway hyper-reactivity (AHR) and inflammation in mouse models of allergic airway disease (AAD), associated with induction of Foxp3+ regulatory T cells (Treg). Using DEREG (DEpletion of REGulatory T cell) mice, in which endogenous Treg can be ablated with Diphtheria toxin (DTx) treatment, we demonstrate that IVIg generates a de novo population of induced Treg (iTreg) in the absence of endogenous Treg. IVIg-generated iTreg were sufficient for inhibition of ovalbumin-induced AHR in an antigen-driven murine model of AAD. In the absence of endogenous Treg, IVIg failed to confer protection against AHR and airway inflammation. Adoptive transfer of purified IVIg-generated iTreg prior to antigen challenge effectively prevented airway inflammation and AHR in an antigen-specific manner.
Peripherally Generated Foxp3<sup>+</sup> Regulatory T Cells Mediate the Immunomodulatory Effects of IVIg in Allergic Airways Disease.
Specimen part
View SamplesMicroRNAs inhibit gene expression by recruiting the RNA-induced silencing complex (RISC) to mRNAs in a process termed RNA interference (RNAi). While it is generally accepted that RNAi modulates gene expression pervasively, the number of mRNAs bound and repressed by miRNAs in vivo in individual cell types remains unknown, with estimates ranging from a few hundred genes to many thousands. We examined microRNA activities in primary cells by combining genetic loss of function with RNA-sequencing, quantitative proteomics and High-Throughput Sequencing of RNA isolated by Crosslinking Immunoprecipitation (HITS-CLIP), focusing on miR-144/451, the most highly expressed microRNA locus during red blood cell (RBC) formation. We show that Argonaute (Ago) protein binds over one thousand different mRNAs in a miR-144/451-dependent manner, accounting for one third of all Ago-bound mRNAs. However, only about 100 mRNAs are stabilized in RBC precursors after ablation of the miR-144/451 locus. Thus, Ago-miRNA complexes destabilize only a small subset of bound mRNAs, probably no more than a few hundred in erythroblasts under physiological conditions. Our integrated approach identified more than 50 new miR-144/451 target mRNAs, including Cox10, which facilitates assembly of the mitochondrial cytochrome c oxidase (COX) electron transport complex. Loss of miR-144/451 resulted in increased Cox10 expression, accumulation of the COX complex, and increased mitochondrial membrane potential with no change in mitochondrial mass. Thus, miR-144/451 represses mitochondrial respiration during erythropoiesis by inhibiting Cox10. Overall design: HITS-CLIP analysis of 3 WT mice fetal livers vs 3 miR-144/451 KO mice fetal livers
Regulation of gene expression by miR-144/451 during mouse erythropoiesis.
Cell line, Subject
View Samples5 day RNAi treatment to knockdown Enigma, CG9006, a Drosophila mitochondrial protein with homology to acyl-CoA dehydrogenases.
Enigma, a mitochondrial protein affecting lifespan and oxidative stress response in Drosophila.
No sample metadata fields
View SamplesMuscle stem cells (MuSC) change molecular and functional properties during development. Using a transgenic Tg:Pax7-nGFP mice, we FACS-isolated MuSC from embryonic (E12.5) and foetal (E17.5) stages to understand the differences and similarities amongst the myogenic stem/progenitor populations.
Cell-autonomous Notch activity maintains the temporal specification potential of skeletal muscle stem cells.
Specimen part
View SamplesMouse neural stem cells were generated from conditional knockout mice (Cicflox/flox) or the wild trype control mice (Cic+/+). Cic is conditionally knocked out following expression of Cre-recombinase. Cre-recombinase was incorporated in vitro via adenoviral-Cre transduction.
<i>Cic</i> Loss Promotes Gliomagenesis via Aberrant Neural Stem Cell Proliferation and Differentiation.
Specimen part
View SamplesMouse Hammer toe (Hm) shows syndactyly. To reveal the molecular mechanisms of Hm phenotype, we performed microarray analysis to search differencially expressed genes in Hm limb.
Enhancer adoption caused by genomic insertion elicits interdigital <i>Shh</i> expression and syndactyly in mouse.
Specimen part
View SamplesDCD is a gene amplified and overexpressed in a subset of breast tumors acting as a growth and survival factor. Patients with DCD-positive breast cancer have worse prognostic features. To investigate the role of DCD in breast tumorigenesis, we analyzed the consequences of its downregulation in human breast cancer cell lines using three specific shRNA lentivirus vectors. Genes up- and down-regulated by DCD were identified using Affymetrix microarray and analyzed by MetaCore Platform. We found that loss of DCD expression led to reduced cell proliferation, resistance to apoptosis, and suppressed tumorigenesis in immunodeficient mice. Network analysis of gene expression data revealed perturbed ERBB signaling following DCD shRNA expression including changes in the expression of ERBB receptors and their ligands. These findings imply that DCD promotes breast tumorigenesis via modulating the activity of the ERBB signaling pathways. As ERBB signaling is also important for neural survival, HER2+ breast tumors may highjack DCDs neural survival-promoting functions to promote tumorigenesis.
Dermcidin exerts its oncogenic effects in breast cancer via modulation of ERBB signaling.
Cell line
View Samples