We investigated roles of KRAS on stemness maintenance and differentiation propensity in the context of induced pluripotent stem cells (iPSCs) using isogenic KRAS mutant (G13C/WT) and wild-type (WT/WT) iPSCs from the same RAS-associated autoimmune lymphoproliferative syndrome-like disease (RALD) patients. RNA-seq analysis was conducted to compare gene expression profiles of WT/WT and G13C/WT iPS cells after in vitro differentiation. We found some differences of gene expression profiles regarding stemness and linage markers in the two genotypes. Overall design: To investigate the changes of stemness and linage markers between KRAS mutant and wild-type iPSCs after differentiation, the iPSCs were differentiated for 16 days . Two clones were used for each genotype (WT/WT and G13C/WT) before and after differentiation, resulting in total 8 conditions.
Status of KRAS in iPSCs Impacts upon Self-Renewal and Differentiation Propensity.
Subject
View SamplesEicosanoids are potent regulators of gene expression of inflammatory cells. Pro- (leukotrienes B4 and C4) and anti-indflammatory (lipoxins A4 and B4) eicosanoids have been described in the literature but the detailed impact of these lipid mediators on the gene expression pattern of monocytic cells has not been studied in detail. We cultured the permanent monocytic cell line MonoMac 6 for 12 h in the absence (solvent control) and presence of these eicosanoids and quantified the differential gene expression patterns using the microarray technology.
Gene expression alterations of human peripheral blood monocytes induced by medium-term treatment with the TH2-cytokines interleukin-4 and -13.
No sample metadata fields
View SamplesTranscriptomal comparison between group 2 innate lymphoid cells (ILC2s) in the murine small intestine (SI-ILC2s) and those in white adipose tissue (WAT-ILC2s). Overall design: mRNA profiles of group 2 innate lymphoid cells (ILC2s) sort-purified from small intestinal lamina propria and mesenteric white adipose tissue of 9-week-old wild type (WT) mice were generated by sequencing, in duplicate, using Illumina HiSeq1500.
Innate Lymphoid Cells in the Induction of Obesity.
Age, Specimen part, Subject
View SamplesIn osteosarcoma patients, the development of metastases, often to the lungs, is the most frequent cause of death. To improve this situation, a deeper understanding of the molecular mechanisms governing osteosarcoma development and dissemination and the identification of novel drug targets for an improved treatment are needed. Towards this aim, we characterized osteosarcoma tissue samples compared to primary osteoblast cells using Affymetrix HG U133A microarrays.
De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway.
No sample metadata fields
View SamplesThe aim of the study was to identify markers for the early diagnosis of endoprosthesis loosening, for the differentiation between wear-particle induced and septic loosening, as well as to gather new insights into the pathogenesis.
Gene expression in endoprosthesis loosening: chitinase activity for early diagnosis?
Sex, Age
View SamplesTo study the role Cnot3 in early B cells development, RNASeq analysis of pro-B cells (B220+ and CD43+) was performed in tamoxifen treated Cnot3(fl/fl) RERTCre and Cnot3+/+;RERTCre mice. Overall design: Two individual replicates of Cnot3(fl/fl) RERTCre and Cnot3(+/+) RERTCre mice were tamoxifen treated periodically. Ten days after the initial treatment, B220+CD43+ pro-B cells were sorted from the bone marrow and RNASeq analysis was performed.
Interaction of CCR4-NOT with EBF1 regulates gene-specific transcription and mRNA stability in B lymphopoiesis.
Specimen part, Cell line, Subject
View SamplesApela (also referred to as Elabela, Ende and Toddler) is a small signaling peptide that activates the G protein-coupled receptor Aplnr. We used CRISPR/Cas9 to generate a null, reporter-expressing allele, in order to study the role of Apela in the developing mouse embryo. We found that loss of Apela results in low penetrance cardiovascular defects that manifest after the onset of circulation. Targeted Apela null alleles exhibited different transcriptional activity depending on the presence or absence of a Neomycin selection cassette. These are referred to as Apela KO NEO-IN and Apela KO NEO-OUT strains, respectively. Despite subtle phenotypic characteristics that were unique to the NEO-OUT mutants, both Apela null strains shared the same variable expressivity of cardiovascular defects and the same penetrance of embryonic lethality. To investigate the earliest regulatory events leading to physical abnormalities in Apela mutants, we performed RNA-Seq on whole stage-matched and morphologically normal E7.5 embryos (3 wild-type, 6 Apela KO NEO-IN, and 6 Apela KO NEO-OUT individuals). We chose this stage because Apela is initially expressed in the embryo at late gastrulation, shortly after the emergence of extraembryonic mesoderm progenitors. Since modification of the Apela locus may influence the expression of neighboring genes, we examined the expression of upstream and downstream sequences and found no significant difference in their expression. Downregulated genes of interest included several mitochondrial genes, Ceacam2, Ulk4, and Mov10l1. Upregulated genes included the vascular endothelial growth factor Vegfc. Principal component analysis identified outliers (KO1 and KO9), both of which expressed lower levels of mesoderm markers. KO9 was further characterized by aberrant upregulation of erythroid and myeloid markers. This finding was confirmed in our study by qRT-PCR analysis of additional Apela null individuals. Overall design: 15 individual embryos were analyzed at E7.5. Embryos were stage-matched according to morphological landmarks. Control samples were wild-type (n=3), and Apela KO samples were null embryos from the NEO-IN (n=6, ‘KO1-6’) and NEO-OUT (n=6, ‘KO7-12) mutant strains. Whole embryos (including embryonic and extraembryonic tissues) were used for the analysis. Apela KO samples were isolated from homozygous KO intercrosses and therefore did not require genotyping.
Loss of Apela Peptide in Mice Causes Low Penetrance Embryonic Lethality and Defects in Early Mesodermal Derivatives.
Specimen part, Cell line, Subject
View SamplesGastric cancer is one of the most common causes of cancer-related deaths worldwide. The lymph node status represents the strongest prognostic factor. Due to its extremely poor prognosis, the identification of novel therapeutic targets is urgently needed. Therefore, we aimed to assess differentially expressed genes in nodal negative versus nodal positive intestinal type gastric carcinoma by GeneChip array technique. The transcriptional profile of 6 gastric cancers with and without lymphatic dissemination was analyzed. A total of 115 transcripts were found to be up- and 219 to be down-regulated in node positive compared with node negative gastric cancers. Next we searched for differentially expressed GPCRs. We identified 52 GPCRs and GPCR-related genes, which were up- or down-regulated with a fold change factor greater 1.5.
Vascular CXCR4 expression - a novel antiangiogenic target in gastric cancer?
Sex, Age, Specimen part
View SamplesA significant fraction of breast cancers exhibit de novo or acquired resistance to estrogen deprivation.
A kinome-wide screen identifies the insulin/IGF-I receptor pathway as a mechanism of escape from hormone dependence in breast cancer.
Cell line, Treatment
View SamplesMycobacteria-induced apoptosis of macrophages plays an important role in modulation of the host immune response involving TNF-alpha as major cytokine. The underlying mechanisms are still ill-defined. Here, we show for the first time that methylglyoxal (MG) and AGEs levels were elevated during mycobacterial infection of macrophages and that their increased levels mediated mycobacteria-induced apoptotic and immune response of macrophages. Moreover, we show that high levels of AGEs were formed at the sites of pulmonary tuberculosis. This observation represents the first evidence of the potential involvement of AGEs in tuberculosis and in infectious diseases in general. Global gene expression profiling of MG-treated macrophages reveals diversified potential roles of MG in cellular processes, including apoptosis, immune response, and growth regulation. The results of this study provide new insights into intervention strategies to develop therapeutic tools against infectious diseases in which MG and AGE production plays critical roles.
Critical role of methylglyoxal and AGE in mycobacteria-induced macrophage apoptosis and activation.
No sample metadata fields
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