Purpose: The goal of this study is to investigate the role of CBS enzyme in colorectal carcinogenesis Methods: RNA-Seq transcriptome analysis of CBS-overexpression in NCM356 cels compared to control vector cells Overall design: RNA-seq transcriptome profiling of NCM356-CBS overexpressing cells vs. vector cells
Upregulation of Cystathionine-β-Synthase in Colonic Epithelia Reprograms Metabolism and Promotes Carcinogenesis.
Subject
View SamplesLow-dose IL-2 represents an immunotherapy to selectively expand regulatory T cells (Tregs) to promote tolerance in patients with autoimmunity. In this article, we show that a fusion protein (FP) of mouse IL-2 and mouse IL-2Ra (CD25), joined by a noncleavable linker, has greater in vivo efficacy than rIL-2 at Treg expansion and control of autoimmunity. Biochemical and functional studies support a model in which IL-2 interacts with CD25 in the context of this FP in trans to form inactive head-to-tail dimers that slowly dissociate into an active monomer. In vitro, IL-2/CD25 has low sp. act. However, in vivo IL-2/CD25 is long lived to persistently and selectively stimulate Tregs. In female NOD mice, IL-2/CD25 administration increased Tregs within the pancreas and reduced the instance of spontaneous diabetes. Thus, IL-2/CD25 represents a distinct class of IL-2 FPs with the potential for clinical development for use in autoimmunity or other disorders of an overactive immune response. Overall design: Splenic murine Tregs mRNA profiles of IL-2/CD25 (FP) or control PBS injected mice were generated 72 hrs post injection by deep sequencing, in quadruplicate (FP) or triplicate (PBS), using NextSeq 500 with a High Output Kit 150-cycle flow cell (Illumina). Reads from RNA-seq were mapped to the Mus musculus genome GRCm38 using STAR (ver.2.5.0) aligner 44. Raw counts were generated on Ensembl gene (GENCODE M13) with featureCounts (ver.1.5.0) 45. Differential expressed genes in Tregs between the IL2/CD25 and PBS injected mice were identified using DESeq2 46, and determined according to threshold of false discovery rate (FDR) <0.05
IL-2/CD25: A Long-Acting Fusion Protein That Promotes Immune Tolerance by Selectively Targeting the IL-2 Receptor on Regulatory T Cells.
Specimen part, Cell line, Subject
View SamplesIxodes species ticks are competent vectors of tick-borne viruses including tick-borne encephalitis and Powassan encephalitis. Tick saliva has been shown to facilitate and enhance viral infection. This likely occurs by saliva-mediated modulation of host responses into patterns favorable for viral infection and dissemination. Because of the rapid kinetics of tick-borne viral transmission, this modulation must occur as early as tick attachment and initiation of feeding. In this study, the gene expression profile of cutaneous bite-site lesions created by uninfected ticks were analyzed at 1, 3, 6, and 12 hours after Ixodes scapularis nymphal tick attachment to discover host pathways or responses potentially important in tick-borne viral establishment.
Early immunologic events at the tick-host interface.
Specimen part, Time
View SamplesThe purpose of this study was to determine and clarify the retinoic effect on the gene expression profile for mouse dendritic cells.
Retinoic acid promotes the development of Arg1-expressing dendritic cells for the regulation of T-cell differentiation.
Specimen part
View SamplesTGF is one of most intensively studied regulators of extracellular matrix formation, and has been implicated in the development of pulmonary fibrosis in different models. However, little is know about the role of miRNAs in TGF mediated fibrogenic gene regulation. By using miRNA qRT-PCR array, we have identified miRNAs whose expression are regulated by TGF in IMR-90 cells. Among those down-regulated miRNAs are miR-29 family members. Knockdown miR-29 in IMR-90 cells results in up-regulation of a large number of extracellular matrix and fibrogenic genes including family members of collagen, laminin, integrin, ADAM and MMP, many of them are predicted or confirmed miR-29 targets. Hierarchichal clustering analysis of mRNA array data revealed that many extracellular matrix and fibrogenic genes up-regulated by TGF in IMR-90 cells, are also up-regulated in miR-29 KD cells. Moreover, the similar set of extracellular matrix and fibrogenic genes is also significantly up-regulated in bleomycin treated mouse lungs. Together, our data strongly suggest that downstream of the TGF, miR-29 is a master modulator of genes involved in extracellular matrix formation and might play a significant role in pulmonary fibrosis.
miR-29 is a major regulator of genes associated with pulmonary fibrosis.
Specimen part, Cell line
View SamplesTumor cells have an increased need for amino acids. Mammalian cells cannot synthesize essential amino acids; they must obtain these amino acids via specific transporters. Glutamine, though a non-essential amino acid, is critical for tumor cells (glutamine addiction). Entry of amino acids into tumor cells is enhanced by upregulation of specific transporters. If the transporters that are specifically induced in tumor cells are identified, blockade of the induced transporters would constitute a logical strategy for cancer treatment.
Deletion of the amino acid transporter Slc6a14 suppresses tumour growth in spontaneous mouse models of breast cancer.
Age, Specimen part
View SamplesWe have carried out transcriptional profile analysis in macroH2A knockdown cells (Namalwa B cells and HeLa cells) and demonstrated that this histone variant plays positive and negative roles in transcription. We also demonstrated the role of macroH2A in regulating the response to Sendai Virus infection.
Composite macroH2A/NRF-1 Nucleosomes Suppress Noise and Generate Robustness in Gene Expression.
Cell line, Treatment
View SamplesSTAT5 interacts with other factors to control transcription, and the mechanism of regulation is of interest as constitutive active STAT5 has been reported in malignancies. Here LSD1 and HDAC3 were identified as novel STAT5a interacting partners in pro-B cells. Characterization of STAT5a, LSD1 and HDAC3 target genes by ChIP-seq and RNA-seq revealed gene subsets regulated by independent or combined action of the factors and LSD1/HDAC3 to play dual role in their activation or repression. Genes bound by STAT5a alone or in combination with weakly associated LSD1 or HDAC3 were enriched for the canonical STAT5a dimer motif, and such binding induced activation or repression. Strong STAT5 binding was seen more frequently in intergenic regions, which might function as distal enhancer elements. Genes bound weakly by STAT5a and strongly by LSD1/HDAC3 present a STAT5a monomer like motif, and are differentially regulated based on their biological role, genomic binding localization and affinity. STAT5a binding in monomer like motifs was found with increased frequency in promoters, indicating a requirement for stabilization by additional factors, which might recruit LSD1/HDAC3. Our study describes an interaction network of STAT5a/LSD1/HDAC3 and a dual function of LSD1/HDAC3 on STAT5-dependent transcription, defined by protein-protein interactions, genomic binding positions-affinities and motifs. Overall design: Mouse pro-B Ba/F3 cells treated with lentiviral vectors expressing short-hairpins to knock-down various genes (STAT5a, STAT5b, LSD1 and HDAC3). All KDs were analysed versus cells treated with lentiviral construct expressing a No-Target short-hairpin at the same condition (either minus [IL3 deprivation for 6h] or plus [IL3 deprivation for 6h and IL3 stimulation for 30min]). Wild-type cells were also generated and compared between the two conditions. All samples contain biological replicates (3-5 depending on the sample).
The dual role of LSD1 and HDAC3 in STAT5-dependent transcription is determined by protein interactions, binding affinities, motifs and genomic positions.
Cell line, Treatment, Subject
View SamplesWe applied next-generation sequencing to investigate the gene expression profiles in mouse bone-marrow derived macrophages with or without long noncoding RNA-Malat1 knockdown. We identified a number of differentially regulated genes in cells with Malat1 knockdown. Overall design: Mouse bone-marrow derived macrophages were transfected with Antisense LNAâ„¢ GapmeRs against Malat1 or Negative Control oligos (Exiqon). 48h after transfection, total RNA was isolated and subjected to high-throughput sequencin (RNA-seq), using Illumina GAIIx. Gene expression profiles were compared between two groups.
Long noncoding RNA Malat1 regulates differential activation of macrophages and response to lung injury.
Specimen part, Cell line, Subject
View SamplesThis is the expression dataset for two studies: 1) Characterization of visceral and subcutaneous adipose tissue transcriptome and biological pathways in pregnant and non-pregnant women: Evidence for pregnancy-related regional-specific differences in adipose tissue and 2) Characterization of visceral and subcutaneous adipose tissue transcriptome in pregnant women with and without spontaneous labor at term: Implication of alternative splicing in the metabolic adaptations of adipose tissue to parturition.
Characterization of visceral and subcutaneous adipose tissue transcriptome in pregnant women with and without spontaneous labor at term: implication of alternative splicing in the metabolic adaptations of adipose tissue to parturition.
Specimen part, Disease stage, Subject
View Samples