ZBTB20 is an adjuvant-specific factor for long-term antibody responses. This factor is critical for maintaining long-lived plasma cells in alum-adjuvanted antibody responses but is dispensable for TLR ligand-adjuvanted responses.
Adjuvant-specific regulation of long-term antibody responses by ZBTB20.
Specimen part
View SamplesGjd3-CreEGFP mice is a novel genetic tool to study the structural and molecular signatures of Atrioventricular Node (AVN) at a high resolution. Overall design: Focusing on the cardiac conduction system, we developed and rigorously characterized a geentic tool Gjd3-CreEGFP to perform in-depth analysis of AVN structure and composition. Utilizing this AVN-specific mouse model, we performed scRNA-Seq on neonatal Gjd3-CreEGFP mice to guide our single-cell atlas of the Atrio-ventricular conduction system (AVCS).
Using Gjd3-CreEGFP mice to examine atrioventricular node morphology and composition.
Specimen part, Subject
View SamplesG-CSF treatment targets CXCL12-abundant reticular (CAR) cells to suppress their production of a number of B trophic factors, including CXCL12, IL-6, IL-7, IGF-1, and Flt3 ligand.
Granulocyte colony-stimulating factor reprograms bone marrow stromal cells to actively suppress B lymphopoiesis in mice.
Treatment
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Definition of the landscape of promoter DNA hypomethylation in liver cancer.
Specimen part, Cell line, Subject
View SamplesExtensive loss of DNA methylation is a hallmark of cancer. The role of hypomethylation in altering gene expression in cancer cells has been poorly understood. Hepatic cellular carcinoma (HCC) is one of the most common human cancers. We use HCC as a model to investigate hypomethylation in cancer by a combination of methylated DNA immunoprecipitation and hybridization with comprehensive promoter arrays. We identify approximately 2,800 promoters that are hypomethylated in tumor samples. The hypomethylated promoters appear in clusters across the genome suggesting a high-level organization behind the epigenomic changes in cancer. The genes whose promoters are demethylated are mainly involved in cell growth, cell adhesion and communication, signal transduction, mobility and invasion; functions that are essential for cancer progression and metastasis. Previous studies suggested that MBD2 was involved in demethylation of uPA and MMP2 genes in human breast and prostate cancer cell lines. We extend these results here showing that whereas MBD2 depletion in normal liver cells has little or no effect, its depletion in the human hepatocellular carcinoma cell line HepG2 and the adenocarcinoma cell line SkHep1 results in suppression of cell growth, anchorage-independent growth and invasiveness, as well as an increase in promoter methylation and silencing of several of the genes that are hypomethylated in tumors. Our studies establish for the first time the rules governing hypomethylation of promoters in liver cancer and define the potential functional role of hypomethylation in cancer.
Definition of the landscape of promoter DNA hypomethylation in liver cancer.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Combinatorial recruitment of CREB, C/EBPβ and c-Jun determines activation of promoters upon keratinocyte differentiation.
Specimen part, Treatment
View SamplesCombinatorial recruitment of CREB, C/EBPb and Jun determines activation of promoters upon keratinocyte differentiation
Combinatorial recruitment of CREB, C/EBPβ and c-Jun determines activation of promoters upon keratinocyte differentiation.
Specimen part, Treatment
View SamplesWe have identified loss of deiminated MA-Brent-1 (an RNA and export binding protein) in the retinal ganglion cells (RGCs) in multiple sclerosis and in glaucoma eyes compared to normal controls. Deimination refers to posttranslational modification of protein bound arginine (not free arginine) in citrulline. Our preliminary studies suggest binding of different repertoire of RNA by non-deiminated and deiminated MA-Brent-1. In vitro, in neurites of cultured RGCs and hippocampal neurons, the select mRNA translation is enhanced by addition of deiminated but not non-deiminated MA-Brent-1. These observations suggest that lack of deiminated MA-Brent-1 has consequences for protein synthesis, remodeling and plasticity of RGCs/neurons. Identification of RNA species bound by deiminated and non-deiminated MA-Brent-1 will enable us there further verification and determining the role that deimination plays in biological function of MA-Brent-1 in multiple sclerosis and glaucoma. To summarize identification of RNA species bound by deiminated and non deiminated MA-Brent-1 will enable us to gain further insight into role of deimination in the overall disease process.
The role of deimination in ATP5b mRNA transport in a transgenic mouse model of multiple sclerosis.
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View SamplesANGPTL4 regulates plasma triglyceride levels by inhibiting lipoprotein lipase. Inactivation of ANGPTL4 decreases plasma triglycerides and reduces risk of coronary artery disease. Unfortunately, targeting ANGPTL4 for the therapeutic management of dyslipidemia and atherosclerosis is hampered by the observation that mice and monkeys in which ANGPTL4 is inactivated exhibit lipid accumulation in mesenteric lymph nodes. In mice these pathological events exclusively unfold upon feeding a high saturated fatty acid diet and are followed by an ultimately lethal pro-inflammatory response and chylous ascites. Here we show that Angptl4-/- mice fed a diet rich in trans fatty acids develop numerous lipid-filled giant cells in their mesenteric lymph nodes, yet do not have elevated serum amyloid and haptoglobin, do not exhibit ascites, and survive, unlike Angptl4-/- mice fed a saturated fatty acid-rich diet. In RAW264.7 macrophages the saturated fatty acid palmitate markedly increases markers of inflammation and the unfolded protein response, whereas the trans-unsaturated elaidate and the cis-unsaturated oleate have the opposite effect. In conclusion, trans and saturated fatty acids have very distinct biological effects. Furthermore, lipid accumulation in mesenteric lymph nodes is uncoupled from activation of an acute-phase response and chylous ascites, suggesting that ANGPTL4 should not be fully dismissed as target for dyslipidemia.
Feeding <i>Angptl4</i><sup>-/-</sup> mice <i>trans</i> fat promotes foam cell formation in mesenteric lymph nodes without leading to ascites.
Specimen part, Cell line
View SamplesSeveral homeobox genes belonging to HD-ZIP I subfamily are highly induced by drought stress at various developmental stages in rice. To analyze the role of a candidate HD-ZIP I subfamily member, OsHOX24, we constitutively overexpressed it in rice. The physiological analyses revealed that overexpression of OsHOX24 gene reduced drought stress tolerance in transgenic plants as compared to wild-type.
Over-Expression of <i>OsHOX24</i> Confers Enhanced Susceptibility to Abiotic Stresses in Transgenic Rice via Modulating Stress-Responsive Gene Expression.
Specimen part
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