In order to investigate the role of reptin methylation on the expression of hypoxia-responsive genes across the whole genome, we performed a microarray analysis from RNAs isolated from MCF7 cells expressing either control shRNA (shRNA) or reptin shRNA (shreptin) in normoxic and hypoxic conditions.
Negative regulation of hypoxic responses via induced Reptin methylation.
Specimen part, Cell line
View SamplesUsing RNA-seq, we report here that BM-MSC cells have a distinct transcriptomic signature and express a unique cluster of transcripts in response to 4 hrs polyIC (10 ug/ml). Overall design: Examination of effects of PolyIC-stimulated BM-MSCs, were generated by deep sequencing on an Illumina HiSeq 2500 (101 cycles PE lane).
Epigenetic regulation of IFITM1 expression in lipopolysaccharide-stimulated human mesenchymal stromal cells.
Specimen part, Treatment, Subject
View SamplesUsing RNA-seq, we report here that BM-MSC cells have a distinct transcriptomic signature and express a unique cluster of transcripts in response to 4 hrs LPS. Overall design: Examination of effects of LPS-stimulated BM-MSCs, were generated by deep sequencing on an Illumina HiSeq 2000(101 cycles PE lane).
Epigenetic regulation of IFITM1 expression in lipopolysaccharide-stimulated human mesenchymal stromal cells.
Treatment, Subject
View SamplesUsing RNA-seq, we report here that BM-MSC cells have a distinct transcriptomic signature and express a unique cluster of transcripts in response to 4 hrs Poly(I:C) (10ug/ml) Overall design: Examination of effects of LPS-stimulated BM-MSCs, were generated by deep sequencing on an Illumina HiSeq 2500(101 cycles PE lane).
Epigenetic regulation of IFITM1 expression in lipopolysaccharide-stimulated human mesenchymal stromal cells.
Specimen part, Treatment, Subject
View SamplesWe report specific changes in schizophrenia developmental interneurons by genome-wide transcriptome analysis. Overall design: RNA sequencing analysis (bulk) of healthy control interneurons vs. schizophrenia interneurons. Fourteen independent iPSC lines per group with two independent differentiations
Dysregulated protocadherin-pathway activity as an intrinsic defect in induced pluripotent stem cell-derived cortical interneurons from subjects with schizophrenia.
Specimen part, Disease, Subject
View SamplesWe report down-regulation of protocadeherins in schizophrenia interneurons by genome-wide transcriptome analysis. Overall design: RNA sequencing analysis (bulk) of healthy control interneurons vs. schizophrenia interneurons. Four independent iPS lines per group (total 8 iPSC lines) with three independent differentiations
Dysregulated protocadherin-pathway activity as an intrinsic defect in induced pluripotent stem cell-derived cortical interneurons from subjects with schizophrenia.
Specimen part, Disease, Subject
View SamplesThe edible mushroom Agaricus blazei Murill has immunomodulating and antiproliferative effects. In a clinical study 33 patients with multiple myeloma were randomized to receive treatment with Agaricus (16 patients) or placebo (17 patients) in addition to chemotherapy.
Immunomodulatory effects of the Agaricus blazei Murrill-based mushroom extract AndoSan in patients with multiple myeloma undergoing high dose chemotherapy and autologous stem cell transplantation: a randomized, double blinded clinical study.
Specimen part, Treatment, Subject, Time
View SamplesCytokine-induced signal transduction is executed by natural biological switches, which among many others control immune related processes. To construct a biological device, that simulates cytokine signaling, we utilized nanobodies to generate synthetic cytokine receptors (SyCyR). High affinity GFP- and mCherry-nanobodies were selected and extracellularly fused to trans-membrane and intracellular domains of IL-23 cytokine receptors. Soluble homo- and heterodimeric GFP:mCherry fusion proteins served as SyCyR ligands. Heterodimeric GFP-mCherry and homodimeric GFP fusion proteins efficiently phenocopied IL-23 signal transduction, respectively, as demonstrated by STAT3-, ERK- and Akt-activation, SOCS3 expression and transcriptome profiling. Interestingly, the homodimeric GFP fusion protein induced IL-23 receptor homo-dimerization and activation of IL-23-like signal transduction
Synthetic cytokine receptors transmit biological signals using artificial ligands.
Specimen part, Cell line
View SamplesLasting B-cell persistence depends on survival signals that are transduced by cell surface receptors. Here, we describe a novel biological mechanism essential for survival and homeostasis of normal peripheral mature B cells and chronic lymphocytic leukemia (CLL) cells, regulated by the heparin-binding cytokine, midkine (MK), and its proteoglycan receptor, the receptor-type tyrosine phosphatase zeta (RPTP). We demonstrate that MK initiates a signaling cascade leading to B cell survival, by binding to RPTP. In mice lacking PTPRZ, the proportion and number of the mature B cell population is reduced. Our results emphasize a unique and critical function for MK signaling in the previously described MIF/CD74 induced survival pathway. Stimulation of CD74 with MIF leads to c-Met activation, resulting in elevation of MK expression in both normal mouse splenic B and CLL cells. Our results indicate that MK and RPTP are important regulators of the B cell repertoire. These findings could pave the way towards understanding the mechanisms shaping B cell survival, and suggest novel therapeutic strategies based on the blockade of the midkine/RPTP-dependent survival pathway.
The cytokine midkine and its receptor RPTPζ regulate B cell survival in a pathway induced by CD74.
Age
View SamplesChronic lymphocytic leukemia (CLL) is characterized by the accumulation of CD5+ B lymphocytes in peripheral blood, lymphoid organs and BM. The main feature of the disease is accumulation of the malignant cells due to decreased apoptosis. CD84 belongs to the Signaling Lymphocyte Activating Molecule (SLAM) family of immunoreceptors, and has an unknown function in CLL cells. Here, we show that the expression of CD84 is significantly elevated from the early stages of the disease, and is regulated by macrophage migration inhibitory factor (MIF) and its receptor, CD74. Activation of cell surface CD84 initiates a signaling cascade that enhances CLL cell survival. Both immune-mediated neutralization or blockade of CD84 induce cell death in vitro and in vivo. In addition, analysis of samples derived from an on-going clinical trial, in which human subjects were treated with humanized anti-CD74 milatuzumab shows a decrease in CD84 mRNA levels milatuzumab-treated cells. This downregulation was correlated with reduction of Bcl-2 and Mcl-1 message. Thus, our data show that overexpression of CD84 in CLL is an important survival mechanism that appears to be an early event in the pathogenesis of the disease. These findings suggest novel therapeutic strategies based on the blockade of this CD84-dependent survival pathway.
CD84 is a survival receptor for CLL cells.
Disease
View Samples