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GSE48438
Mus musculus
10 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Multipotent stromal cells (MSC) and their osteoblastic lineage cell (OBC) derivatives are part of the bone marrow (BM) niche and contribute to hematopoietic stem cell (HSC) maintenance. During myeloproliferative neoplasm (MPN) development, MSCs are stimulated to overproduce functtionally altered OBCs, which accumulate in the BM cavity as myelofibrotic cells. These MPN-expanded OBCs, in turn, impair the maintenance of normal HSCs but not of leukemic stem cells.
Publication Title
Myeloproliferative neoplasia remodels the endosteal bone marrow niche into a self-reinforcing leukemic niche.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 574 Downloadable Samples
Illumina HiSeq 2500
Description
Single cell RNA Seq and bioinformatic analysis are used to study what processes are important for the molecular reprogramming of GMPs after 5-FU treatment. Samples were collected at different time points (0, 8, 10, 12 and 14 days post treatment) Overall design: Single cell RNA sequencing of GMP cells upon 5-FU treatment
Publication Title
Myeloid progenitor cluster formation drives emergency and leukaemic myelopoiesis.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
The goal of this study is to compare tumor-infiltrating antigen presenting cell populations by global transcriptome profiling (RNA-seq) to help further delineate sub-populations of infiltrating myeloid cells in tumor. Methods: Four tumor antigen presenting cell populations were sorted from digested B78chOVA (melanoma variant) tumors in biological triplicate Results: RNA was extracted from the 4 groups (n=3 per group) and prepared for RNAseq. Sequencing yielded ~405 million reads with an average read depth of 33.7 million reads/sample. Reads were then aligned to the mouse genome (UCSC mm10) and those that mapped uniquely to known mRNAs were used to assess differential expression. Overall design: Examination of four tumor infiltrating myeliod populations
Publication Title
Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 4000
Description
Intratumoral stimulatory dendritic cells (SDCs) play an important role in locally restimulating cytotoxic T cells and driving immune responses against cancer. However, the mechanisms that control SDC numbers remain poorly understood. In human melanoma, SDC numbers correlated with intratumoral expression of the gene encoding the cytokine FLT3LG, and we subsequently found in mouse and human tumors that this cytokine was predominantly produced by lymphocytes, notably including natural killer (NK) cells. NK cells stably formed conjugates with SDCs in the mouse tumor microenvironment (TME) and genetic and cellular ablation of NK cells in mice demonstrated their importance in regulation of SDC numbers through production of Flt3L. Although anti-PD-1 “checkpoint” immunotherapy for cancer largely targets T cells, we found that NK cells correlated with protective SDCs in human cancers, with patient responsiveness to anti-PD-1 immunotherapy, and with better overall survival. Our studies reveal that innate immune SDCs and NK cells cluster together as the best prognostic tool for T cell directed immunotherapy and that these innate cells are necessary for enhanced T cell tumor responses, suggesting this axis for novel therapies. Overall design: This dataset is n=11 biologically independent metastatic melanoma samples from patient tumors. There is no control dataset.
Publication Title
A natural killer-dendritic cell axis defines checkpoint therapy-responsive tumor microenvironments.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 30 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
This study aimed at investigating the impact of chronic ingestion of sebacic acid (SA), a 10 carbons medium-chain dicarboxylic acid, on glycemic control in a mouse model of type 2 diabetes (db/db mice). Three groups of 15 mice were fed for 6 weeks either a chow diet (Ctrl), or a chow diet supplemented with 1.5% or 15% (SA1.5% and SA15% resp.) energy from SA. Fasting glycemia was measured once a week and HbA1c before and after supplementation. An oral glucose tolerance test (OGTT) was performed at the end of the supplementation. Gene expression was determined by transcriptomic analysis on the liver of the Ctrl and SA15% groups. Results-After 42 days of supplementation, fasting glycemia and HbA1c were ~70% and ~25% lower in the SA15% group compared to other groups showing a beneficial effect of SA on hyperglycemia. During OGTT, blood glucose area under the curve (AUC) was reduced after SA15% compared to other groups. This effect was associated with a tendency for an improved insulin response. In the liver, Pck1 and FBP mRNA were statistically decreased in the SA15% compared to Ctrl suggesting a reduced hepatic glucose output induced by SA. Conclusions-Dietary supplementation of SA largely improves glycemic control in a mouse model of type 2 diabetes. This beneficial effect may be due (1) to a reduced hepatic glucose output resulting from transcriptional down regulation of key gluconeogenesis genes and (2) to an improved glucose induced-insulin secretion.
Publication Title
Six weeks' sebacic acid supplementation improves fasting plasma glucose, HbA1c and glucose tolerance in db/db mice.
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- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Post-hybridization washing is an essential part of microarray experiments. Both, the quality of the experimental washing protocol and the adequate consideration of washing in intensity calibration ultimately affect the quality of the expression estimates extracted from the microarray intensities. We conducted experiments on GeneChip microarrays with altered protocols for washing, scanning and staining to study the probe-level intensity changes as a function of washing cycles. Particularly, three Affymetrix GeneChip HGU133plus2 arrays were hybridized and equilibrated for 16 hours in the hybridization oven. For one of the three arrays washing and staining was performed according to the manufacturers instructions. For another array the first scan was done immediately after low stringent wash and staining without intermitting stringent washing. Then, the array was stringently washed and scanned in alternating order three more times where each washing step consists of a definite number of washing cycles. The third array was low stringently washed followed by two stringent washing cycles and staining before the first scan. Subsequently it was analogously processed as array A. All three chips are repeatedly processed in a second series of alternating wash/scan-cycles which was performed using the same protocol for each chip as in the first series as described above. As in the first series the arrays were also stained a second time to compensate for any loss of bleached fluorescent dye. Analysis of the washing kinetics shows that the signal-to-noise ratio doubles roughly every ten stringent washing cycles. Washing can be characterized by time-dependent rate constants which reflect the heterogeneous character of target binding to microarray probes. We propose an empirical washing function which estimates the survival of probe bound targets. The washing function allows calibrating probe intensities for the effect of washing. On a relative scale, proper calibration for washing markedly increases expression measures especially in the limit of small and large values.
Publication Title
Washing scaling of GeneChip microarray expression.
Sample Metadata Fields
Cell line
View Samples