Right ventricular dysfunction (RVD) independently predicts worse outcomes in both heart failure (HF) and pulmonary hypertension (PH), irrespective of their etiologies. Yet no evidence-based therapies exist for RVD and progression towards RV failure (RVF) can occur in spite of optimal medical treatment of HF or PH. This disparity reflects our insufficient understanding of the molecular pathophysiology of RVF. To identify molecular mechanisms that may uniquely underlie RVF, we investigated the cardiac ventricular transcriptome of advanced HF patients, with and without RVF. Using weighted gene co-expression network and module-phenotype analyses, we identified a 279-member gene module that correlated significantly and specifically with RVF. Within this module, WIPI1 served as a genetic hub, HSPB6, SNAP47, and MAP4 as drivers, and PRDX5 as a repressor of RVF. We subsequently confirmed the ventricular specificity and temporal relationship of Wipi1, Hspb6, and Map4 transcript expression changes in murine models of pressure overload induced RV failure versus LV failure and subsequently uncovered differential dysregulation of autophagy in the failing RV versus the failing LV, namely a shift towards excessive non-canonical, Beclin1-independent, Wipi1/LC3II-mediated autophagy in RVF. In vitro siRNA silencing of Wipi1 partially protected isolated neonatal rat ventricular cardiac myocytes against aldosterone-induced failing phenotype. Moreover, silencing Wipi1 blunted mitochondrial superoxide production and limited non-canonical autophagy in this in vitro RVF model. Our findings suggest that Wipi1 regulates mitochondrial oxidative signaling and autophagy in cardiac myocytes. Inhibition of Wipi1 may hold promise as a therapeutic target for RVF. Overall design: Examination of RNAseq results from Left and Right Ventricles of 15 individuals, 5 control, 5 left-sided Heart Failure, 5 bi-ventricular Heart Failure
WIPI1 is a conserved mediator of right ventricular failure.
Specimen part, Subject
View SamplesHuman NK cells were sorted into CD56dim and CD56bright NK cell subpopulations. In order to define characteristics of both populations gene profiling was performed using Affymetrix arrays U133a and U133B.
Gene and protein characteristics reflect functional diversity of CD56dim and CD56bright NK cells.
Specimen part
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ChIP-on-chip analysis identifies IL-22 as direct target gene of ectopically expressed FOXP3 transcription factor in human T cells.
Cell line
View SamplesThe transcription factor (TF) Forkhead Box P3 (FOXP3) is constitutively expressed in high levels in natural occurring CD4+CD25+ regulatory T cells (nTreg) and is not only the most accepted marker for that cell population, but is considered lineage determinative. Chromatin immunoprecipitation (ChIP) of transcription factors in combination with genomic tiling microarray analysis (ChIP-on-Chip) has been shown to be an appropriate tool to identify FOXP3 transcription factor binding sites (TFBS) on a genome-wide scale. In combination with microarray expression analysis the ChIP-on-Chip technique allows to identify direct FOXP3 target genes. This dataset shows expression data of resting and mitogen stimulated (PMA / ionomycin) retrovirally transduced Jurkat T cells either expressing FOXP3(2) (J-FOXP3) or an empty vector control (J-GFP).
ChIP-on-chip analysis identifies IL-22 as direct target gene of ectopically expressed FOXP3 transcription factor in human T cells.
Cell line
View SamplesExperimental Design
Quorum-sensing antagonistic activities of azithromycin in Pseudomonas aeruginosa PAO1: a global approach.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The oscillating miRNA 959-964 cluster impacts Drosophila feeding time and other circadian outputs.
Specimen part
View SamplesUsing high throughput sequencing of Drosophila head RNA, a small set of miRNAs that undergo robust circadian oscillations in levels were discovered. We concentrated on a cluster of six miRNAs, mir-959-964, all of which peak at about ZT12 or lights-off. The data indicate that the cluster pri-miRNA is transcribed under bona fide circadian transcriptional control and that all 6 mature miRNAs have short half-lives, a requirement for oscillating. Manipulation of food intake dramatically affects the levels and timing of cluster miRNA transcription with no more than minor effects on the core circadian oscillator. This indicates that the central clock regulates feeding, which in turn regulates proper levels and cycling of the cluster miRNAs. Viable Gal4 knock-in as well as cluster knock-out and over-expression strains were used to localize cluster miRNA expression as well as explore their functions. The adult head fat body is a major site of expression, and feeding behavior, innate immunity, metabolism, and perhaps stress responses are under cluster miRNA regulation. The feeding behavior results indicate that there is a feedback circuit between feeding time and cluster miRNA function as well as a surprising role of post-transcriptional regulation in these behaviors and physiology.
The oscillating miRNA 959-964 cluster impacts Drosophila feeding time and other circadian outputs.
Specimen part
View SamplesUsing high throughput sequencing of Drosophila head RNA, a small set of miRNAs that undergo robust circadian oscillations in levels were discovered. We concentrated on a cluster of six miRNAs, mir-959-964, all of which peak at about ZT12 or lights-off. The data indicate that the cluster pri-miRNA is transcribed under bona fide circadian transcriptional control and that all 6 mature miRNAs have short half-lives, a requirement for oscillating. Manipulation of food intake dramatically affects the levels and timing of cluster miRNA transcription with no more than minor effects on the core circadian oscillator. This indicates that the central clock regulates feeding, which in turn regulates proper levels and cycling of the cluster miRNAs. Viable Gal4 knock-in as well as cluster knock-out and over-expression strains were used to localize cluster miRNA expression as well as explore their functions. The adult head fat body is a major site of expression, and feeding behavior, innate immunity, metabolism, and perhaps stress responses are under cluster miRNA regulation. The feeding behavior results indicate that there is a feedback circuit between feeding time and cluster miRNA function as well as a surprising role of post-transcriptional regulation in these behaviors and physiology. Overall design: Six samples of small RNA libraries (RNA size 19 to 29 nucleotides long) were prepared from Drosophila heads, each collected at one circadian time point during a light-dark cycle (ZT0, ZT4, ZT8, ZT12, ZT16, ZT20).
The oscillating miRNA 959-964 cluster impacts Drosophila feeding time and other circadian outputs.
Specimen part, Cell line, Subject
View SamplesTo determine whether adding Decipher to standard risk stratification tools (CAPRA-S and Stephenson nomogram) improves accuracy in prediction of metastatic disease within 5 years after surgery in men with adverse pathologic features after RP.
A genomic classifier improves prediction of metastatic disease within 5 years after surgery in node-negative high-risk prostate cancer patients managed by radical prostatectomy without adjuvant therapy.
Age
View SamplesUterine macrophages are thought to play an important regulatory role at the maternal-fetal interface. We report here a unique gene expression pattern intrinsic of first trimester decidual monocytes/macrophages, but not of their blood counterparts. The micro-array data comprises approximately 14,000 genes. Some of the key findings were confirmed by real time PCR or secreted protein measurements. A large number of regulated genes were found to be functionally related to immunomodulation and tissue remodelling, corroborating polarization patterns of differentiated macrophages of M2 phenotype. These include M2 markers such as CCL-18, CD209, insulin-like growth factor (IGF)-1, mannose receptor c type (MRC)-1 and fibronectin-1. Further, the selective up-regulation of triggering receptor expressed on myeloid cells (TREM)-2, alpha-2-macroglobulin (A2M) and prostaglandin D2 synthase (PGDS) provides new insights into the regulatory function of decidual macrophages in pregnancy. In addition, a large number of regulated genes in the micro-array analysis were related to cell cycle regulation. Taken together, molecular characterization of decidual macrophages presents a unique transcriptional profile replete with important components for fetal immunoprotection.
Gene expression profiling of human decidual macrophages: evidence for immunosuppressive phenotype.
Specimen part
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