Digital gene expression tag profiling of P19CL6 cell model during differentiation to cardiomyocytes Overall design: Four replicates were anlyzed at five time-points during differentiation; day 1, day 4, day 7, day 10 and day 14. Spontanously beating cardiomyocytes was observed at day 14 Spreadsheet with Log2 difference expression values is filtered by FDR and thus incomplete.
TGF-β signaling is associated with endocytosis at the pocket region of the primary cilium.
Cell line, Subject, Time
View SamplesHuman prolactinomas (n=4, 3 males and 1 female) were obtained during trans-sphenoidal surgery as part of an ongoing accession of human pituitary tumors. The study was approved Institutional Review Board (IRB) of Emory University, and informed consent obtained for all subjects. Tumors were microdissected and removed using the surgical microscope, rinsed in sterile saline, snap-frozen in liquid nitrogen, and stored (-80 ) until analysis. Each tumor fragment was confirmed independently by a neuropathologist by histology and immunohistochemistry prior to molecular analysis. Three normal pituitary glands from cadavers were obtained from the National Resource Center (NDRI, www.ndriresource.org). Each human tissue sample was analyzed using Affymetrix Human Genome U95Av2 arrays.
Genomic characterization of human and rat prolactinomas.
Sex, Specimen part
View SamplesBromodomain and extra terminal domain (BET) proteins are important epigenetic regulators facilitating the transcription of genes in chromatin areas linked to acetylated histones. JQ1, a BET protein inhibitor, has antiproliferative activity against many cancers, mainly through inhibition of c-MYC and upregulation of p21. In this research, we investigated the use of JQ1 for human osteosarcoma (OS) treatment. JQ1 significantly inhibited the proliferation and survival of OS cells inducing G1 cell cycle arrest, premature senescence, but little effect on apoptosis. Interestingly, c-MYC protein levels in JQ1-treated cells remained unchanged, whereas the upregulation of p21 protein was still observable. Although effective in vitro, JQ1 alone failed to reduce the size of the MNNG/HOS xenografts in immunocompromised mice. To overcome the resistance of OS cells to JQ1 treatment, we combined JQ1 with rapamycin, an mTOR inhibitor. JQ1 and rapamycin synergistically inhibited the growth and survival of OS cells in vitro and in vivo. We also identified that RUNX2 is a direct target of BRD4 inhibition by JQ1 in OS cells. Chromatin immunoprecipitation (ChIP) showed that enrichment of BRD4 protein around RUNX2 transcription start sites diminished with JQ1 treatment in MNNG/HOS cells. Overexpression of RUNX2 protected JQ1-sensitive OS cells from the effect of JQ1, and siRNA-mediated inhibition of RUNX2 sensitized the same cells to JQ1. In conclusion, our findings suggest that JQ1, in combination with rapamycin, is an effective chemotherapeutic option for OS treatment. We also show that inhibition of RUNX2 expression by JQ1 partly explains antiproliferative activity of JQ1 in OS cells.
Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma.
Specimen part, Cell line
View SamplesRenal hypoxia is widespread in acute kidney injury (AKI) of various aetiologies. Hypoxia adaptation, conferred through the hypoxia-inducible factor (HIF), appears to be insufficient. Here we show that HIF activation in renal tubules through Pax8-rtTA-based inducible knockout of von Hippel-Lindau protein (VHL-KO) protects from rhabdomyolysis-induced AKI. In this model, histological observations indicate that injury mainly affects proximal convoluted tubules, with 5% necrosis at d1 and 40% necrosis at d2. HIF-1alpha up-regulation in distal tubules reflects renal hypoxia. However, lack of HIF in proximal tubules suggests insufficient adaptation by HIF.
Tubular von Hippel-Lindau knockout protects against rhabdomyolysis-induced AKI.
Specimen part, Disease, Disease stage, Treatment
View SamplesThe circadian clock controls a wide variety of metabolic and homeostatic processes in a number of tissues, including the kidney. However, the role of the renal circadian clocks remains largely unknown. To address this question we performed transcriptomic analysis in mice with inducible and conditional ablation of the circadian clock system in the renal tubular cells (Bmal1lox/lox/Pax8-rtTA/LC1 mice). Deep sequencing of the renal transcriptome revealed significant changes in the expression of genes related to metabolic pathways and organic anion transport. In parallel, kidneys from Bmal1lox/lox/Pax8-rtTA/LC1 mice exhibited a significant decrease in the NAD+/NADH ratio suggesting an increased anaerobic glycolysis and/or decreased mitochondrial function. In-depth analysis of two selected pathways revealed (i) a significant increase in plasma urea levels correlating with increased renal arginase 2 (Arg2) activity, hyperargininemia and increase of the kidney arginine content; (ii) a significantly increased plasma creatinine concentration and reduced capacity of the kidney to secrete anionic drugs (furosemide), paralleled by a ~80% decrease in the expression levels of organic anion transporter OAT3 (SLC22a8). Collectively, these results indicate that the renal circadian clocks control a variety of metabolic/homeostatic processes at both the intra-renal and systemic levels and are involved in drug disposition. Overall design: Mice with a specific ablation of the Arntl gene encoding BMAL1 in the renal tubular cells were compared to wild-type littermate at ZT4 and ZT16 (ZT – Zeitgeber time units; ZT0 is the time of light on and ZT12 is the time of light off).
Nephron-Specific Deletion of Circadian Clock Gene Bmal1 Alters the Plasma and Renal Metabolome and Impairs Drug Disposition.
Specimen part, Subject, Time
View SamplesPARK2 (PARKIN) is an E3 ubiquitin ligase whose dysfunction has been associated with the progression of Parkinsonism and human malignancies, and its role in cancer remains to be explored. In this study, we investigated its role in glioma.
Genomic and Functional Analysis of the E3 Ligase PARK2 in Glioma.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
LPS independent activation of the pro-inflammatory receptor Trem1 by C/EBPε in granulocytes.
Specimen part
View SamplesTo identify target genes of C/EBPepsilon in differentiated granulocytes, total RNA were purified from sorted Gr-1intermediate/Mac-1+ and Gr-1hi/Mac-1+ cells of C/EBPepsilon knock out and C57BL/6 wild type mice using RNeasy Mini Kit (Qiagen). The differences of their expression pattern were compared with Illumina Mouse WG-6v2 Expression Chip platform. Raw Illumina BeadArray data in IDAT format were preprocessed using the open-source Bioconductor package illuminaio with the Illumina array design formation BGX file downloaded from NCBI, GEO accession: GPL6887. Following the preprocessing, the expression data were normalized by applying control background correction, log transformation and inter-quantile normalization using the neqc function from the limma bioconductor package. This allowed us to compare the transcriptomic consequences of C/EBPepsilon in two independent populations.
LPS independent activation of the pro-inflammatory receptor Trem1 by C/EBPε in granulocytes.
Specimen part
View SamplesIn order to investigate the function of Bach2 in pre-B ALL, we isolated bone marrow cells from wildtype and Bach2 knockout mice of C57Bl6 background and transformed them with BCR-ABL1.
Mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia.
Age, Specimen part, Disease, Disease stage, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia.
Specimen part
View Samples