In two disparate models, we show that rapid revaccination following sublethal gamma radiation exposure rescues memory CD8+ T cell Responses.
Rescue of CD8+ T cell vaccine memory following sublethal γ irradiation.
No sample metadata fields
View SamplesWe used a combination of genome-wide and promoter-specific DNA binding and expression analyses to assess the functional roles of Myod and Myog in regulating the program of skeletal muscle gene expression. Our findings indicate that Myod and Myog have distinct regulatory roles at a similar set of target genes. At genes expressed throughout the program of myogenic differentiation, Myod can bind and recruit histone acetyltransferases. At early targets, Myod is sufficient for near full expression; whereas, at late expressed genes Myod initiates regional histone modification but is not sufficient for gene expression. At these late genes, Myog does not bind efficiently without Myod, however, transcriptional activation requires the combined activity of Myod and Myog. Therefore, the role of Myog in mediating terminal differentiation is, in part, to enhance expression of a subset of genes previously initiated by Myod.
Global and gene-specific analyses show distinct roles for Myod and Myog at a common set of promoters.
No sample metadata fields
View SamplesMustard and Kenny mutants are resistant to oral infection with V.cholerae. We used microarrays to determine whether Key and Mtd have overlapping regulons.
The Drosophila protein mustard tailors the innate immune response activated by the immune deficiency pathway.
Specimen part
View SamplesRegulatory T cells (Treg) are pivotal for the maintenance of peripheral tolerance by controlling self-reactive, chronic and homeostatic T cell responses. We now report that the increase in Treg suppressive function observed in lymphopenic mice correlates with the degree of lymphopenia and is caused by a higher frequency of a novel subpopulation of CD103posICOSpos cells among peripheral Treg that differentially express multiple Treg signature genes.
A subpopulation of CD103(pos) ICOS(pos) Treg cells occurs at high frequency in lymphopenic mice and represents a lymph node specific differentiation stage.
Sex, Age, Specimen part
View SamplesT cells in mucosal tissues fulfill a complex array of duties to ensure maintenance of barrier immunity. In oral mucosa tissue, we found that increased inflammation altered CD4 T cell subsets in a spatially-dependent manner, although it had a modest effect on the frequency of tissue-resident memory T cells (TRM) and the CD4 T cell transcriptome. In contrast, localization to the tissue profoundly altered the transcriptional profile, emphasizing the importance of studying healthy tissue to understand disease-specific changes. Our data revealed the existence of a TH17 cell population that is predominantly found in the tissue-resident, but not transient, CD4 T cell compartment in mucosal tissue. Overall design: This project contains bulk RNA-seq data from paired oral mucosa tissue and blood CD4 T cell subsets from 10 subjects and 10X genomics sequencing of CD4 T cell subsets from one individual
The human tissue-resident CCR5<sup>+</sup> T cell compartment maintains protective and functional properties during inflammation.
Specimen part, Subject
View SamplesProgenitors in human vasculature expanded in-vitro were differentiated with adipogenic cocktail for 12 days, following which they were stimulated with forskolin for 7 days
Human 'brite/beige' adipocytes develop from capillary networks, and their implantation improves metabolic homeostasis in mice.
Specimen part, Treatment
View SamplesRecent studies have reported that glycosphingolipids (GSL) might be involved in obesity induced insulin resistance. Those reports suggested that inhibition of GSL biosynthesis in animals ameliorated insulin sensitivity accompanied with improved glycemic control leading to decreased liver steatosis in obese mice. In addition, GSL depletion altered hepatic secretory function. In those studies, ubiquitously acting inhibitors for GSL-biosynthesis have been used to inhibit function of the enzyme Ugcg (UDP-glucose:ceramide glucosyltransferase), catalyzing the first step of the glucosylceramide based GSL-synthesis pathway. In the present study, a genetic approach for GSL deletion in hepatocytes was chosen to achieve full inhibition of GSL synthesis and to prevent possible adverse effects caused by Ugcg-inhibitors. Using the Cre/loxP system under control of the albumin promoter, GSL biosynthesis in hepatocytes and their release into the plasma could be effectively blocked. Deletion of GSL in hepatocytes did not change quantity of bile excretion through the biliary duct. Total bile salt content in bile-, feces- and plasma from mutant mice showed no difference as compared to control animals. Cholesterol concentration in liver-, bile-, feces- and plasma-samples remained unaffected. Lipoprotein concentration in plasma-samples in mutant animals reached similar levels as in their control littermates. No alteration in glucose tolerance after intraperitoneal application of glucose and insulin appeared in mutant animals. A preventive effect of GSL-deficiency on development of liver steatosis after high fat diet feeding could not be observed.
Hepatic glycosphingolipid deficiency and liver function in mice.
No sample metadata fields
View SamplesBrdt is a testis specific member of a family of chromatin interacting proteins. All of the family members have been shown to regulate transcription. Brdt is highly expressed in round spermatids, and may play a role in transcriptional regulation in these cells.
The testis-specific double bromodomain-containing protein BRDT forms a complex with multiple spliceosome components and is required for mRNA splicing and 3'-UTR truncation in round spermatids.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Multi-OMIC profiling of survival and metabolic signaling networks in cells subjected to photodynamic therapy.
Cell line, Treatment
View SamplesPhotodynamic therapy (PDT) is a tumor treatment strategy that relies on the production of reactive oxygen species (ROS) in the tumor following local illumination. Although PDT has shown promising results in the treatment of non-resectable perihilar cholangiocarcinoma, it is still employed palliatively. In this study, tumor-comprising cells (i.e., cancer cells, endothelial cells, macrophages) were treated with the photosensitizer zinc phthalocyanine that was encapsulated in cationic liposomes (ZPCLs). Post-PDT survival pathways were studied following sublethal (50% lethal concentration (LC50)) and supralethal (LC90) PDT using a multi-omics approach. ZPCLs did not exhibit toxicity in any of the cells as assessed by toxicogenomics. Sublethal PDT induced survival signaling in perihilar cholangiocarcinoma (SK-ChA-1) cells via mainly hypoxia-inducible factor 1 (HIF-1)-, nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-B)-, activator protein 1 (AP-1)-, and heat shock factor (HSF)-mediated pathways. In contrast, supralethal PDT damage was associated with a dampened survival response. (Phospho)proteomic and metabolomic analysis showed that PDT-subjected SK-ChA-1 cells downregulated proteins associated with epidermal growth factor receptor (EGFR) signaling, particularly at LC50. PDT also affected various components of glycolysis and the tricarboxylic acid cycle as well as metabolites involved in redox signaling. In conclusion, sublethal PDT activates multiple pathways in tumor parenchymal and non-parenchymal cells that, in tumor cells, transcriptionally regulate cell survival, proliferation, energy metabolism, detoxification, inflammation/angiogenesis, and metastasis. Accordingly, sublethally afflicted tumor cells are a major therapeutic culprit. Our multi-omics analysis unveiled multiple druggable targets for pharmacological intervention.
Multi-OMIC profiling of survival and metabolic signaling networks in cells subjected to photodynamic therapy.
Cell line, Treatment
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