Myeloid derived suppressor cells (MDSC) playing the immune suppressive roles in tumor bearing host consists of two major subsets of granulocytic and monocytic cells. Granulocytic MDSC (G-MDSC) express CD11b+ Gr-1high Ly6G+ Ly6Clow and produce high level of reactive oxygen species (ROS). Interestingly, neutrophils are well known ROS producing cells during immune defensive process and share same surface markers with G-MDSC. These similar features always brought the fundamental questions whats the difference between G-MDSC and neutrophils but its not yet proven clearly.
Characterization of the nature of granulocytic myeloid-derived suppressor cells in tumor-bearing mice.
Sex, Specimen partView Samples
Dendritic cells (DC) arise from a diverse group of hematopoietic progenitors and have marked phenotypic and functional heterogeneity. We have found previously that activation of protein kinase C beta 2 (PRKCB2) by cytokines or phorbol esters drives normal human CD34(+) hematopoietic progenitors and myeloid leukemic blasts (KG1, K562 cell lines, and primary patient blasts) to differentiate into DC, but the genetic program triggered by PRKCB2 activation that results in DC differentiation is only beginning to be characterized. Of the cPKC isoforms, only PRKCB2 was consistently activated by DC differentiation-inducing stimuli in normal and leukemic progenitors. To examine early changes in gene expression following PRKCB2 activation, we employed the following cell lines: (1) the CD34(+) human acute myeloid leukemia derived cell line KG1, which undergoes DC differentiation following phorbol ester treatment; (2) KG1a, a spontaneously arising differentiation-resistant daughter cell line of KG1 that has lost PRKCB2 expression; (3) clones established from KG1a that stably express exogenous PRKCB2-GFP fusion proteins and are once again able to undergo DC differentiation (KG1a-PRKCB2-GFP Clone E9 and Clone E11). We examined changes in gene expression in these cells following treatment with the phorbol ester PMA (phorbol 12-myristate 13-acetate) for 2 hours. Since KG1 and KG1a differ in PRKCB2 expression but have similar expression of the other protein kinase C isoforms, this protocol will allow for the identification of genes regulated by PRKCB2 activation.
Tumor-induced STAT3 signaling in myeloid cells impairs dendritic cell generation by decreasing PKCβII abundance.
Sex, Age, Specimen part, Cell line, TreatmentView Samples
The role of myeloid cells as regulators of tumor progression that significantly impact the efficacy of cancer immunotherapies makes them an attractive target for inhibition. Here we explore the effect of a novel, potent, and selective inhibitor of serine/threonine protein kinase CK2 on modulating myeloid cells in the tumor microenvironment. Although inhibition of CK2 caused only a modest effect on dendritic cells in tumor-bearing mice, it substantially reduced the amount of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) and tumor-associated macrophages (TAM). This effect was not caused by the induction of apoptosis, but rather by a block of differentiation. Our results implicated downregulation of CCAAT-enhancer binding protein-a (C/EBPa) in this effect. Although CK2 inhibition did not directly affect tumor cells, it dramatically enhanced the antitumor activity of immune checkpoint receptor blockade using anti-CTLA-4 antibody. These results suggest a potential role of CK2 inhibitors in combination therapies against cancer. Overall design: Untreated and CK2 inhibitor treated hematopoietic progenitor cells cells assayed by RNA-seq
Inhibition of Casein Kinase 2 Disrupts Differentiation of Myeloid Cells in Cancer and Enhances the Efficacy of Immunotherapy in Mice.
Specimen part, Cell line, SubjectView Samples
The bone marrow niche plays a critical role in controlling the fate of hematopoietic stem cells (HSCs) by integrating intrinsic and extrinsic signals. However, the molecular events in the HSC niche remain to be investigated. Here, we report that intercellular adhesion molecule-1 (ICAM-1) maintains HSC quiescence and repopulation capacity in the niche. ICAM-1-deficient mice (ICAM-1-/-) displayed significant expansion of phenotypic long-term HSCs with impaired quiescence, as well as favors myeloid cell expansion. ICAM-1-deficient HSCs presented normal reconstitution capacity during serial transplantation; however, reciprocal transplantation experiments showed that ICAM-1 deficiency in the niche impaired HSCs quiescence and repopulation capacity. In addition, ICAM-1 deletion caused failure to retain HSCs in the bone marrow and changed the expression profile of stroma cell-derived factors, possibly representing the mechanism for defective HSCs in ICAM-1-/- mice. Collectively, these observations identify ICAM-1 as a regulator in the bone marrow niche. Overall design: WT donor LSK (Ly5.1+) were sorted after transplanted into WT (n=3) or ICAM-1-/- (n=3) recipients (Ly5.2+) for 8 weeks, we analysis the transcriptional profile of LSK hematopoietic stem cells after transplantation by High-throughput RNA-sequencing.
ICAM-1 Deficiency in the Bone Marrow Niche Impairs Quiescence and Repopulation of Hematopoietic Stem Cells.
Specimen part, Cell line, SubjectView Samples
To investigate the effects of quality of fat in a high fat diet (HFD) over time on hepatic lipid storage and transcriptome in mice.
Eicosapentaenoic and docosahexaenoic acid-enriched high fat diet delays the development of fatty liver in mice.
Sex, Specimen part, TimeView Samples
Identifying molecular effects between herring and beef diet in Ldlr-/- mice
Identifying molecular effects of diet through systems biology: influence of herring diet on sterol metabolism and protein turnover in mice.
Specimen partView Samples
We analyzed the global effect of c-Myb knockdown by sequencing the transcriptomes of K-562 cells transfected with control siRNA and si2992 (MYB knockdown), as well as K-562 cells stably expressing TY-tagged wild type c-Myb and c-Myb D152V transfected with si2992 Overall design: Cells were tranfected with siRNA and 24 hours after total RNA was extracted. Three individual experiments were performed. Libraries were prepared and 125-bp paired-end reads were obtained using an Illumina HiSeq 2500 sequencer
A c-Myb mutant causes deregulated differentiation due to impaired histone binding and abrogated pioneer factor function.
Specimen part, Cell line, SubjectView Samples
In the present study, we have investigated the effect of CpG Oligodeoxynucleotides (CpG-ODN) on the outcome of Plasmodium infection of the mosquito vectors Anopheles stephensi and Anopheles gambiae and on the modulation of mosquito immunity to Plasmodium. Anopheles mosquitoes inoculated with CpG-ODN showed significant reduction of Plasmodium infection rate and intensity. Microarrays were used to profile transcription of fat-body from CpG-ODN-treated mosquitoes. Mosquitoes were dissected 18h after ODN inoculation (immediately before feeding). Batches of 20 to 30 fat bodies (abdomen without midgut, ovaries and malpighian tubule]) were dissected in cold DEPC-treated phosphate-buffered saline (PBS) and processed for RNA preparation. Mosquitoes treated with CpG-ODNs are less susceptible to Plasmodium infection. Transcription profile of fat body indicates that protection was associated with coagulation/wound healing, while melanization appears to be depressed.
CpG-containing oligodeoxynucleotides increases resistance of Anopheles mosquitoes to Plasmodium infection.
Sex, Specimen part, TreatmentView Samples
A biobank collection of carotid plaque samples taken from patients undergoing endarterectomy operations.
Prediction of ischemic events on the basis of transcriptomic and genomic profiling in patients undergoing carotid endarterectomy.
Specimen part, Disease, SubjectView Samples
Smoking is a major risk factor for Urothelial carcinoma (UC). However the complex mechanisms, how smoking promotes carcinogenesis and tumour progression, remain obscure. A microarray based approached was therefore performed to detect the smoking derived gene expression alteration in non-malignant and malignant urothelial tissues from patients with superficial or invasive UC. Smoking enhanced cell migration and response to tissue damages. In non-malignant tissues smoking induced immune response and altered the cytoskeleton. In urothelial carcinoma, smoking altered extracellular and chromosome structures. Smoking affected tissues from patients with invasive carcinomamore strongly, up-regulating particularly growth factors and oncogenes in non-malignant tissue of patients with invasive but not with superficial carcinoma. In former smokers, comparable changes were seen in tissues form patients with invasive disease while they were minor or reversed in tissue of patients with superficial disease. Best but not complete tissue repair was suggestedfor non-malignant tissue from patients with superficial tumours.
New insights into the influence of cigarette smoking on urothelial carcinogenesis: smoking-induced gene expression in tumor-free urothelium might discriminate muscle-invasive from nonmuscle-invasive urothelial bladder cancer.
Specimen part, DiseaseView Samples