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GSE59143
Mus musculus
20 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
ABSTRACT:Pregnancy requires a higher functional beta cell mass and this is associated with profound changes in the gene expression profile of pancreatic islets. Taking Tph1 as a sensitive marker for pregnancy-related islet mRNA expression in female mice, we previously identified prolactin receptors and placental lactogen as key signalling molecules. Since beta cells from male mice also express prolactin receptors, the question arose whether male and female islets have the same phenotypic resilience at the mRNA level during pregnancy. We addressed this question in vitro, by using islet tissue culture with placental lactogen and in vivo, by transplanting male or female islets into female acceptor mice. Additionally, the islet mRNA expression of pregnant prolactin receptor deficient mice was compared with that of their pregnant wild-type littermates. When cultured with placental lactogen, or transplanted in female recipients that became pregnant (day 12.5), male islets induced the islet pregnancy gene signature, which we defined as the 12 highest induced genes in non-transplanted female islets at day 12.5 of pregnancy. In addition, serotonin immunoreactivity was also induced in these male transplanted islets at day 12.5 of pregnancy. In order to investigate the importance of prolactin receptors in these mRNA changes we used a prolactin receptor deficient mouse model. For the 12 genes of the signature, which are highly induced in control pregnant mice, no significant induction of mRNA transcripts was found at day 9.5 of pregnancy. Together, our results support the key role of placental lactogen as a circulating factor that can trigger the pregnancy mRNA profile in male and female beta cells.
Publication Title
Prolactin receptors and placental lactogen drive male mouse pancreatic islets to pregnancy-related mRNA changes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
ABSTRACT:Pregnancy requires a higher functional beta cell mass and this is associated with profound changes in the gene expression profile of pancreatic islets. Taking Tph1 as a sensitive marker for pregnancy-related islet mRNA expression in female mice, we previously identified prolactin receptors and placental lactogen as key signalling molecules. Since beta cells from male mice also express prolactin receptors, the question arose whether male and female islets have the same phenotypic resilience at the mRNA level during pregnancy. We addressed this question in vitro, by using islet tissue culture with placental lactogen and in vivo, by transplanting male or female islets into female acceptor mice. Additionally, the islet mRNA expression of pregnant prolactin receptor deficient mice was compared with that of their pregnant wild-type littermates. When cultured with placental lactogen, or transplanted in female recipients that became pregnant (day 12.5), male islets induced the islet pregnancy gene signature, which we defined as the 12 highest induced genes in non-transplanted female islets at day 12.5 of pregnancy. In addition, serotonin immunoreactivity was also induced in these male transplanted islets at day 12.5 of pregnancy. In order to investigate the importance of prolactin receptors in these mRNA changes we used a prolactin receptor deficient mouse model. For the 12 genes of the signature, which are highly induced in control pregnant mice, no significant induction of mRNA transcripts was found at day 9.5 of pregnancy. Together, our results support the key role of placental lactogen as a circulating factor that can trigger the pregnancy mRNA profile in male and female beta cells.
Publication Title
Prolactin receptors and placental lactogen drive male mouse pancreatic islets to pregnancy-related mRNA changes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina HiSeq 2500
Description
Using 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).
Publication Title
Epigenetic regulation of IFITM1 expression in lipopolysaccharide-stimulated human mesenchymal stromal cells.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Using 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).
Publication Title
Epigenetic regulation of IFITM1 expression in lipopolysaccharide-stimulated human mesenchymal stromal cells.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
Using 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).
Publication Title
Epigenetic regulation of IFITM1 expression in lipopolysaccharide-stimulated human mesenchymal stromal cells.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 39 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
ABSTRACT: The human growth hormone (hGH) minigene is frequently used in the derivation of transgenic mouse lines to enhance transgene expression. Although this minigene is present in the transgenes as a secondcistron, and thus not thought to be expressed, we found that three commonly used lines, Pdx1-CreLate, RIP-Cre, and MIP-GFP, each expressed significant amounts of hGH in pancreatic islets. Locally secreted hGH binds to prolactin receptors on cells, activates STAT5 signaling, and induces pregnancy-like changes in gene expression, thereby augmenting pancreatic cell mass and insulin content. In addition, islets of Pdx1-CreLate mice have lower GLUT2 expression and reduced glucose-induced insulin release and are protected against the cell toxin streptozotocin. These findings may be important when interpreting results obtained when these and other hGH minigene-containing transgenic mice are used.
Publication Title
Impaired islet function in commonly used transgenic mouse lines due to human growth hormone minigene expression.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The 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.
Publication Title
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.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Cytokine-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
Publication Title
Synthetic cytokine receptors transmit biological signals using artificial ligands.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Lasting 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.
Publication Title
The cytokine midkine and its receptor RPTPζ regulate B cell survival in a pathway induced by CD74.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Chronic 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.
Publication Title
CD84 is a survival receptor for CLL cells.
Sample Metadata Fields
Disease
View Samples