Fascin, an actin-binding protein, is upregulated in a variety of cancers, including esophageal squamous cell carcinoma (ESCC) and is proposed to function in cellular growth, mobility and invasiveness. Nonetheless, the molecular mechanisms through which fascin expression contributes to the proliferation and invasiveness of ESCC are unknown.
Involvement of CYR61 and CTGF in the fascin-mediated proliferation and invasiveness of esophageal squamous cell carcinomas cells.
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View SamplesErg is an ETS family transcription factor frequently overexpressed in human leukemias and has been implicated as a key regulator of hematopoietic stem cells (HSCs). However how Erg controls normal hematopoiesis, particularly at the stem cell level, remains poorly understood. Using homologous recombination, we generated an Erg knockdown allele (Ergkd) in which Erg expression can be restored upon Cre-mediated excision of a Stopper cassette. In Ergkd/+ mice, ~40% reduction in Erg dosage perturbed both fetal liver and bone marrow hematopoiesis by reducing the numbers of Lin-Sca-1+c-Kit+ (LSK) hematopoietic stem and progenitor cells (HSPCs) and megakaryocytic progenitors.
Reduced Erg Dosage Impairs Survival of Hematopoietic Stem and Progenitor Cells.
Specimen part
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Comprehensive functional characterization of cancer-testis antigens defines obligate participation in multiple hallmarks of cancer.
Cell line, Treatment
View SamplesWe found that the cancer testis antigen, ZNF165, is required for viability and can modulate TGF-induced gene expression in mesenchymal, Claudin-Low, TNBC. We employed the Affymetrix microarray platform to uncover transcriptionally modulated genes following ZNF165 depletion and TGF stimulation using the Claudin-low TNBC tumor-derived cell lines, SUM159 as a model. Our results provide insight into how ZNF165 globally modulates TGF signaling.
Comprehensive functional characterization of cancer-testis antigens defines obligate participation in multiple hallmarks of cancer.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
H3K36 histone methyltransferase Setd2 is required for murine embryonic stem cell differentiation toward endoderm.
Specimen part
View SamplesSETD2/HYPB has been known as a histone H3K36 specific methyltransferase. However, its roles in physiology such as development and cellular function remain unclear. In this study, using mESCs as cellular model, we show that Setd2 mainly regulates differentiation of murine embryonic stem cells (mESCs) towards primitive endoderm. This study aimed at exploring how did Setd2 regulate primitive endoderm. differentiation.
H3K36 histone methyltransferase Setd2 is required for murine embryonic stem cell differentiation toward endoderm.
Specimen part
View SamplesThe mechanisms by which the epidermis responds to disturbances in barrier function and restores homeostasis are unknown. With a disruption of the epidermal barrier, water is lost resulting in an increase in extracellular sodium concentration. We demonstrate that the sodium channel Nax functions as the sodium sensor. With increased extracellular sodium, Nax up-regulates prostasin which results in activation of the sodium channel ENaC, resulting in increased sodium flux and increased downstream mRNA synthesis of inflammatory mediators. The same pathways are present in lung epithelial cells.
Sodium channel Nax is a regulator in epithelial sodium homeostasis.
Sex, Specimen part, Cell line, Treatment, Time
View SamplesUnderstanding the function of individual miRNA species in mice would require the production of hundreds of loss-of-function strains. To accelerate analysis of miRNA biology in mammals, we combined recombinant adeno-associated virus (rAAV) vectors with miRNA ‘Tough Decoys’ (TuDs) to inhibit specific miRNAs. Intravenous injection of rAAV9 expressing anti-miR-122 or anti-let-7 TuD depleted the corresponding miRNA and increased its mRNA targets. rAAV producing anti-miR-122—but not anti-let-7—TuD reduced serum cholesterol by 40% for 18 weeks in wild-type mice and reduced serum LDL by 50% in LDL receptor-deficient mice. High throughput sequencing of liver miRNAs from the treated mice confirmed that the targeted miRNA, but no other miRNAs, were depleted and revealed that TuD RNAs induce miRNA tailing and trimming in vivo. rAAV-mediated miRNA inhibition thus provides a simple way to study miRNA function in adult mammals and a potential therapy for dyslipidemia and other diseases caused by miRNA deregulation. Overall design: Examining the effect of Tough Decoy miRNA inhibitors on miRNA stability and integrity
Long-term, efficient inhibition of microRNA function in mice using rAAV vectors.
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View Sampleswe reporter the transcritional difference after THP-1 cells were infected with HSV-1UL37WT virus or HSV-1UL37C819S virus. Overall design: RNA sequencing of 3 samples with 2 repeats
Species-Specific Deamidation of cGAS by Herpes Simplex Virus UL37 Protein Facilitates Viral Replication.
Specimen part, Cell line, Subject
View SamplesDNA methylation is the net result of deposition by DNA methyltransferases (DNMT1, 3A and 3B) and removal by the Ten-Eleven Translocation 1-3 (TET1-3) family of proteins and/or passive loss by replication. The relative contribution of the individual enzymes and pathways is only partially understood. Here we comprehensively analyzed and mathematically simulated the dynamics of DNA de-methylation during the reprogramming of the hypermethylated serum-cultured mouse embryonic stem cells (ESCs) to the hypomethylated 2i-cultured ground state of mESC. We show that DNA demethylation readily occurs in TET[1-/-, 2-/-] ESCs with similar kinetics as their WT littermates. Vitamin C activation of TET causes accelerated and more profound DNA demethylation without markedly affecting reprogramming kinetics. We developed a mathematical model that highly accurately predicts the global level of 5methyl- and 5hydroxymethylcytosine during the transition. Modeling and experimental validation show that the concentration of DNMT3A and DNMT3B determines the steady state level of global DNA methylation and absence of DNMT3A/B even in continued presence of DNMT1 results in gradual loss of 5mC. Taken together, DNMT1 alone is insufficient to maintain DNA methylation but requires the action of DNMT3A/3B that act as a “dimmer switches”. Overall design: RNA-seq time series was performed during the early time phase of serum to 2i transition in the presence and absence of vitamin C (4h, 16h,24h, 32h), 1 replicate
Impairment of DNA Methylation Maintenance Is the Main Cause of Global Demethylation in Naive Embryonic Stem Cells.
No sample metadata fields
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