Hypoxia, which characterizes most tumor tissues, can alter the function of different immune cell types, favoring tumor escape mechanisms. In this study, we show that hypoxia profoundly acts on NK cells by influencing their transcriptome, affecting their immunoregulatory functions, and changing the chemiotactic responses of different NK cell subsets.
Hypoxia Modifies the Transcriptome of Human NK Cells, Modulates Their Immunoregulatory Profile, and Influences NK Cell Subset Migration.
Specimen part
View SamplesGene expression profiling in arterial tissue from type 2 diabetic patients
Fibulin-1 is a marker for arterial extracellular matrix alterations in type 2 diabetes.
No sample metadata fields
View SamplesWe have shown that activin promoted skin tumorigenesis in mice induced by the human papilloma virus 8 oncogenes. Activin attracted blood monocytes to the skin as revealed by depletion of CCR2-positive monocytes. To determine if activin also altered the gene expression profile of these cells, we performed RNA-Sequencing of macrophages FACS-sorted from the pre-cancerous ear skin. We have found that activin induces a pro-migratiory, pro-angiogenic and pro-tumorigenic genes in skin macrophages in vivo. This largely contributes to the pro-tumorigenic function of activin, since macrophage depletion delayed spontaneous tumorigenesis in HPV8-transgenic mice by reducing keratinocyte proliferation and angiogenesis. Overall design: F4/80+CD11b+CD45+ cells were FACS-sorted from the pre-cancerous ear skin of wt/wt, HPV8/wt, wt/Act and HPV8/Act mice and their expression profile was analysed by RNA-Sequencing. Experiment was performed in triplicates, for each replicate ear skin of 3-6 mice of corresponding genotype was pooled.
Activin promotes skin carcinogenesis by attraction and reprogramming of macrophages.
Specimen part, Cell line, Subject
View SamplesPurpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS transcriptome profiling (RNA-seq) from whole eye, after removal of the lens and cornea from 1-2 month old miR-211-/- mice and compare it with wt mice Methods: Whole eye (after removal of the lens and cornea) mRNA profiles of 1-2 month old wild-type (WT) and neural miR-211-/-mice were generated by deep sequencing, in multiple biological replicates, five for WT and six for miR-211-/- animals, using Illumina GAIIx. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using TaqMan and SYBR Green assays RNA-Seq libraries were prepared from whole eye, after removal of the lens and cornea from miR-211-/- mice. Results: Each library was sequenced using 100 bp paired-end sequencing on the Illumina HiSeq 1000 system. Gene abundances from RNA-Seq data were quantified using RSEM45. Using an optimized data analysis workflow, we mapped about 30 million sequence reads per sample to the mouse genome. This approach yielded read count values for a total of 38253 mouse genes annotated in GenCode. We only considered genes that had at least 1 count per million in at least five out of 11 samples as expressed, yielding a total of 15590 genes. Next we performed differential gene expression analysis to determine the transcriptional effects of miR-211 deletion. This analysis yielded a total of 63 genes that were differentially expressed with a False Discovery Rate (FDR) <0.1 (Fig. 4). Of these, the expression levels of 61 genes were significantly decreased upon miR-211 deletion, while only 2 genes were upregulated. Conclusions: Our study represents the first detailed analysis of whole eye transcriptomes, with biologic replicates, generated by RNA-seq technology on miR-211-/-. Overall design: Whole eye (after removal of the lens and cornea) mRNA profiles of 1-2 month old wild-type (WT) and neural miR-211-/-mice were generated by deep sequencing, in multiple biological replicates, five for WT and six for miR-211-/- animals, using Illumina GAIIx.
MiR-211 is essential for adult cone photoreceptor maintenance and visual function.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The genetic and genomic background of multiple myeloma patients achieving complete response after induction therapy with bortezomib, thalidomide and dexamethasone (VTD).
Specimen part, Disease, Disease stage, Subject
View SamplesThe prime focus of the current therapeutic strategy for Multiple Myeloma (MM) is an early and deep tumour burden reduction; this characterizes and defines the complete response (CR). To date, no description of the characteristics of the plasma cells (PC) prone to achieve CR has been reported. This study aimed at the molecular characterization of PC derived from MM patients who achieved CR after bortezomib-thalidomide-dexamethasone (VTD) first line therapy.
The genetic and genomic background of multiple myeloma patients achieving complete response after induction therapy with bortezomib, thalidomide and dexamethasone (VTD).
Specimen part, Disease, Disease stage
View SamplesEGR3 expression is upregulated in human prostate cancer compared to normal prostate tissue and is associated with absence of relapse, while low EGR3 expression in tumors is predicitive of disease relapse (Pio et al., PLOS One 2013; 8(1):e54096). However the function of EGR3 in prostate cancer is unknown. Human prostate cancer cells M12 containing high levels of EGR3 were used for shRNA-mediated silencing of EGR3. Gene expression analysis of EGR3 knockdown cells reveals a role in inflammation and the existence of a crosstalk with the NFkB pathway.
Early growth response 3 (Egr3) is highly over-expressed in non-relapsing prostate cancer but not in relapsing prostate cancer.
Cell line, Treatment
View SamplesThe anthracycline, doxorubicin (Dox), is widely used in oncology, but it may it may cause a cardiomyopathy which has dismal prognosis and cannot be effectively prevented. The secretome of multipotent human amniotic fluid-derived stem cells (hAFS) has previously been demonstrated to reduce ischemic cardiac damage. Here, it is shown that the hAFS conditioned medium (hAFS-CM) antagonizes senescence and apoptosis of cardiomyocytes and cardiac progenitor cells, two major features of Dox cardiotoxicity. Mechanistic studies with primary mouse neonatal cardiomyocytes reveal that hAFS-CM inhibition of Dox-elicited senescence and apoptosis is paralleled by decreased DNA damage and is associated with nuclear translocation of NF-kB and upregulation of a set of genes controlled by NF-kB, namely Il6 and Cxcl1, which promote cardiomyocyte survival, and Cyp1b1 and Abcb1, which encode for proteins involved in Dox metabolism and efflux, respectively. The PI3K/Akt signaling cascade, upstream of NF-kB, is potently activated by the hAFS-CM and pre-treatment with a PI3K inhibitor abrogates NF-kB accumulation into the nucleus, modulation of its target genes, and prevention of Dox-initiated senescence and apoptosis in response to the hAFS-CM. This work may lay the ground for the development of a stem cell-based paracrine therapy of chemotherapy-related cardiotoxicity.
The human amniotic fluid stem cell secretome effectively counteracts doxorubicin-induced cardiotoxicity.
Specimen part
View SamplesTo examine the molecular phenotype of hypoxic cardiomyocytes in their native environment, we isolated tdTomato+ cardiomyocytes from fresh cryosections using laser microdissection. And perform gene expression analysis using RNA sequencing (RNA-seq).
Hypoxia fate mapping identifies cycling cardiomyocytes in the adult heart.
No sample metadata fields
View SamplesDepending on the tumor type IB kinase (IKK) can act as tumor promoter or tumor suppressor in various malignancies. Here we demonstrate a key function of IKK in the suppression of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKK kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of IFN expressing M1-like myeloid cells. In IKK mutant mice M1-like polarization is not controlled in a cell autonomous manner but depends rather on the interplay of both IKK mutant tumor epithelia and immune cells.
IKKα promotes intestinal tumorigenesis by limiting recruitment of M1-like polarized myeloid cells.
Specimen part, Time
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