This SuperSeries is composed of the SubSeries listed below.
Atrial identity is determined by a COUP-TFII regulatory network.
Age, Specimen part
View SamplesAtria and ventricles exhibit distinct molecular profiles that produce structural and functional differences between the two cardiac compartments. However, factors that determine these differences remain largely undefined. Cardiomyocyte-specific COUP- TFII ablation produces ventricularized atria that exhibit ventricle-like action potentials, increased cardiomyocyte size, and development of extensive T-tubules.
Atrial identity is determined by a COUP-TFII regulatory network.
Age, Specimen part
View SamplesWhile gene expression dynamics have been extensively catalogued during hematopoietic differentiation in the adult, less is known about transcriptome diversity of human hematopoietic stem cells (HSCs) during development. To characterize transcriptional and post-transcriptional changes in HSCs during development, we leveraged high-throughput genomic approaches to profile miRNAs, lincRNAs, and mRNAs. Our findings indicate that HSCs manifest distinct alternative splicing patterns in key hematopoietic regulators. Detailed analysis of the splicing dynamics and function of one such regulator, HMGA2, identified an alternative isoform that escapes miRNA-mediated targeting. We further identified the splicing kinase CLK3 that, by regulating HMGA2 splicing, preserves HMGA2 function in the setting of an increase in let-7 miRNA levels, delineating how CLK3 and HMGA2 form a functional axis that influences HSC properties during development. Collectively, our study highlights molecular mechanisms by which alternative splicing and miRNA-mediated post-transcriptional regulation impact the molecular identity and stage-specific developmental features of human HSCs. Overall design: RNA-seq of HPC-5F cells transduced with a control (CTRL), HMGA2-L (LONG), HMGA2-S (SHORT) or CLK3 ORF lentiviral over-expression vectors.
A CLK3-HMGA2 Alternative Splicing Axis Impacts Human Hematopoietic Stem Cell Molecular Identity throughout Development.
Specimen part, Subject
View SamplesCOUP-TFII, a member of the nuclear receptor superfamily plays a critical role in angiogenesis and organogenesis during embryonic development. Our results indicate that COUP-TFII expression is profoundly upregulated in prostate cancer patients and might serves as biomarker for recurrence prediction. Thus we conduct transcriptome comparison of control and COUP-TFII depleted PC3 cells to gain genomic insights on the biological processes that COUP-TFII is involved in prostate cancer cells. Ingenuity Pathway Analysis (IPA) shows that the most prominent altered pathways in the COUP-TFII depleted cells are related to cell growth; cell cycle progression and DNA damage response. Indeed many growth related genes including E2F1, p21, CDC25A, Cyclin A and Cyclin B are changed in COUP-TFII knockdown cells, suggesting that COUP-TFII might be an important regulator for prostate cancer cell growth. Further functional assays from cells and mice genetic studies confirm the hypothesis that COUP-TFII serve as the major regulator to control prostrate cancer growth. Together, results provide insight into the role of COUP-TFII in prostate tumorigenesis.
COUP-TFII inhibits TGF-β-induced growth barrier to promote prostate tumorigenesis.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Deficiency of the microRNA-31-microRNA-720 pathway in the plasma and endothelial progenitor cells from patients with coronary artery disease.
Specimen part, Treatment, Time
View SamplesEarly EPCs (eEPCs) appear at less than 1 week in culture dishes, whereas late EPCs (LEPCs) appear late at 2-4 weeks. Distinct angiogenic properties between these two EPC subpopulations have been disclosed by the angiogenesis assay: late EPCs, but not eEPCs, form vascular networks de novo and are able to incorporate into vascular networks. On the contrary, eEPCs, but not late ones, indirectly augment tubulogenesis even when physically separated by a Transwell membrane, implying the involvement of a cytokine-based paracrine mechanism.
Deficiency of the microRNA-31-microRNA-720 pathway in the plasma and endothelial progenitor cells from patients with coronary artery disease.
Specimen part, Time
View SamplesHigh glucose impairs the angiogenic activities of late endothelial precursor cells (EPC). We found that far infrared (FIR) treatment restored partially the activity of late EPC. However, the mechanisms are unclear. We performed gene expression microarray analysis to assess the expression profiles of high glucose-treated late EPC with or without FIR treatment.
Deficiency of the microRNA-31-microRNA-720 pathway in the plasma and endothelial progenitor cells from patients with coronary artery disease.
Specimen part, Treatment
View SamplesTazarotene-induced gene 1 (TIG1), also named as retinoic acid receptor responder 1 (RARRES1), is a retinoid inducible type II tumor suppressor gene; the TIG1B isoform inhibits growth and invasion of cancer cells. Expression of TIG1B is frequently downregulated in various cancer tissues; however, the expression and activities of the TIG1A isoform has yet to be analyzed. This study investigated the effects of TIG1A and TIG1B isoforms on gene expression profiles of colon cancer cells. TIG1A, TIG1B and control stable clones derived from HCT116 colon cells were established using the GeneSwitch system. TIG1 isoform expression was induced upon 5 micro Molar of mifepristone (MFP) treatment for 24 hr. Biological triplicate samples were prepared and gene expression profiles were determined by microarray using human genome HGU133 plus 2 array (Affymatrix). Upon induction of TIG1A and TIG1B expression for 24 hr, a total of 129 and 55 genes were significantly altered, respectively. Of the genes analyzed, 23 and 6 genes were up- and downregulated, respectively in both TIG1A and TIG1B expressing cells.
G protein-coupled receptor kinase 5 mediates Tazarotene-induced gene 1-induced growth suppression of human colon cancer cells.
Cell line, Time
View SamplesIn support of the investigation into the response of tissue resident phagocytes to sterile tissue damage in the peritoneal wall, different phagocyte populations were isolated from this tissue and RNA expression was measured using RNAseq. Overall design: Peritoneal wall phagocytes from three Cx3cr1gfp/+Ccr2rfp/+ animals were sorted into Cx3cr1-Ccr2rfp-, Cx3cr1-Ccr2rfp+, and Cx3cr1+Ccr2rfp- groups. Cells from three mice were sorted, and carried through the RNAseq protocol as three replicates per group.
Resident Macrophages Cloak Tissue Microlesions to Prevent Neutrophil-Driven Inflammatory Damage.
Specimen part, Subject
View SamplesCOUP-TFII plays a critical role in angiogenesis during development. It has also been shown to suppress Notch signaling pathway to confer vein identity. However, the downstream targets and the mechanism mediate COUP-TFII function to regulate these processes remain elusive. To identify the downstream targets and the mechanism by which COUP-TFII regulates agiogenesis and vein specification, we knocked down COUP-TFII in HUVEC cells using COUP-TFII specific siRNA and used microarray analysis to identify downstream targets. Interestingly, we found the expression of many genes in the cell cycle pathway and Notch signaling pathway are significantly altered in the COUP-TFII depleted cells.
COUP-TFII is a major regulator of cell cycle and Notch signaling pathways.
Specimen part
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