Vitamin A is the only known compound that produces spontaneous fractures in rats. In an effort to resolve the molecular mechanism behind this effect, we fed young rats high doses of vitamin A and performed a global transcriptional analysis of diaphyseal bone after one week, i.e. just before the first fractures appeared. Microarray gene expression analysis revealed that 68 transcripts were differentially expressed in hypervitaminotic cortical bone and 118 transcripts were found when the bone marrow was also included. 98% of the differentially expressed genes in the bone marrow sample were up-regulated. In contrast, hypervitaminotic cortical bone without marrow showed reduced expression of 37% of differentially expressed genes. Gene Ontology (GO) analysis revealed that only samples containing bone marrow were associated to a GO term, which principally represented extracellular matrix (ECM). This is consistent with the histological findings of increased endosteal bone formation. Four of the genes in this ECM cluster and four other genes, including Cyp26b1 which is known to be up-regulated by vitamin A, were selected and verified by real-time PCR. In addition, immunohistochemical staining of bone sections confirmed that the bone-specific molecule, osteoadherin (Omd) was up-regulated. Further analysis of the major gene expression changes revealed distinct differences between cortical bone and bone marrow, e.g. there appeared to be augmented Wnt signaling in the bone marrow but reduced Wnt signaling in cortical bone. Moreover, induced expression of hypoxia-associated genes was only found in samples containing bone marrow. Together, these results corroborate our previous observations of compartment-specific effects of vitamin A, with reduced periosteal but increased endosteal bone formation, and suggest important roles for Wnt signaling and hypoxia in the processes leading to spontaneous fractures.
Microarray profiling of diaphyseal bone of rats suffering from hypervitaminosis A.
Sex, Age, Specimen part, Disease
View SamplesDNA microarrays were conducted on E. coli K12 cells stressed with 10 M in N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN). Overall, 260 genes varied in expression, 114 up-regulated and 146 down-regulated by Zn deprivation
Characterization of Zn(II)-responsive ribosomal proteins YkgM and L31 in E. coli.
No sample metadata fields
View SamplesWe characterized tumor and immune microenvironment (TiME) of malignant pleural mesothelioma (MPM) using immunoproteomic approach to comprehensively understand the landscape to affect prognosis and possibly to predict response to immunotherapy. Time-of-Flight Mass Cytometry (CyTOF) was performed on the tumors of 12 MPM patients. We comprehensively analyzed TiME by developing intuitive models for visualizing single-cell data with statistical inference and performed unsupervised clustering of cell frequency. A clinically relevant protein signature through mass spectrometry and mRNA transcriptome array was tested for its ability to reflect prognosis in three independent cohorts (n=330) and to predict response to immune checkpoint inhibitor therapy in publicly available data and in 10 patients of MPM treated with anti-PD1 therapy. A systematic understanding of antitumor immunity by immunoproteomic characterization of TiME envisions significant progress in developing rational immunotherapeutic strategies in MPM.
Comprehensive immunoproteogenomic analyses of malignant pleural mesothelioma.
Disease, Disease stage, Treatment
View SamplesThe development of insulin resistance is strongly associated with accumulation of intracellular lipid in tissues outside of adipose including skeletal muscle, liver and heart. In obese humans, intramyocellular lipid (IMCL) is negatively correlated with whole body insulin sensitivity. The skeletal myocyte imports fatty acids (FA) into the cell from circulating free fatty acids or lipoprotein particles such as VLDL, to support energy production. Once transported into the cell, FAs are oxidized for ATP production, used to build membranes, or stored as triglyceride. However, in the long term, increased delivery of fatty acids can exceed mitochondrial oxidative capacity and set the stage for a vicious cycle of cellular lipotoxicity. We have recently identified a novel small molecule inhibitor of lipid accumulation in skeletal mycytes termed SBI-477. Microarray transcriptomics was performed in primary human skeletal myotubes following oleate loading and treatment with SBI-477. This was also compared to A922500, a diacylglycerol transferase 1 (DGAT1) inhibitor. SBI-477 treatment reversed many of the transcriptomic effects of oleate loading in these cells but also produced a transcriptomic profile distinct from the DGAT1 inhibitor.
MondoA coordinately regulates skeletal myocyte lipid homeostasis and insulin signaling.
Treatment
View SamplesWe generated hiPSCs from patients fibloblast with retinitis pigmentosa (RP) using retrovirus and Sendai virus vectors, which we differentiated into hiPSC derived retinal pigment epithelium using two different methods (SDIA and SFEB methods).
Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application.
Cell line
View SamplesWe have generated a molecular taxonomy of lung carcinoma, the leading cause of cancer death in the United States and worldwide. Using oligonucleotide microarrays, we analyzed mRNA expression levels corresponding to 12,600 transcript sequences in 186 lung tumor samples, including 139 adenocarcinomas resected from the lung. Hierarchical and probabilistic clustering of expression data defined distinct subclasses of lung adenocarcinoma. Among these were tumors with high relative expression of neuroendocrine genes and of type II pneumocyte genes, respectively. Retrospective analysis revealed a less favorable outcome for the adenocarcinomas with neuroendocrine gene expression. The diagnostic potential of expression profiling is emphasized by its ability to discriminate primary lung adenocarcinomas from metastases of extra-pulmonary origin. These results suggest that integration of expression profile data with clinical parameters could aid in diagnosis of lung cancer patients.
Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesWe identified SLC44A5 as a gene associated with birth weight in cattle based on genome wide association studies.
The molecular effects of a polymorphism in the 5'UTR of solute carrier family 44, member 5 that is associated with birth weight in Holsteins.
Cell line
View SamplesEarly epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies. The patients with MDS, chronic myelomonocytic leukemia (CMMoL), and high risk AML were treated with sequential administration of methylation inhibitor drugs (5AC and entinostat). To study gene expresion regulation in treated patients, microarray analysis was done on RNA samples extracted from CD34+ cells from 18 patients before and 15 days after treatment using Affymetrix U133Plus2.0.
Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies.
Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Evidence that bovine forebrain embryonic zinc finger-like gene influences immune response associated with mastitis resistance.
No sample metadata fields
View SamplesTo investigate genes that might influence resistance to infection through IGF1R, we screened human breast cancer-derived OCUB-M cells transfected with expression vector encoding IGF1R using microarray analysis.
Evidence that bovine forebrain embryonic zinc finger-like gene influences immune response associated with mastitis resistance.
No sample metadata fields
View Samples