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 SamplesTgif1 is a transcriptional corepressor that limits TGF responsive gene expression. TGF signaling has antiproliferative effects in several cell types, generally resulting in a G1 arrest. Mouse embryo fibroblasts (MEFs) are primary cells with limited life-span, that senesce after several passages in culture.
Premature senescence and increased TGFβ signaling in the absence of Tgif1.
Specimen part
View SamplesWe report RNAseq data from HCT-15 cells were treated wih control(DMSO), GDC-0973, G007-LK and combined GDC-0973 and G007-LK treatmetn for 24 hours. Overall design: Three biological replicates of cultured HCT-15 cells treated with DMSO (0.02%), G007-LK (1µM), GDC-0973 (1µM) or G007-LK and GDC-0973 for 24 hours before Rna extraction
MEK Inhibition Induces Canonical WNT Signaling through YAP in <i>KRAS</i> Mutated HCT-15 Cells, and a Cancer Preventive FOXO3/FOXM1 Ratio in Combination with TNKS Inhibition.
Specimen part, Treatment, Subject
View SamplesWe report the differences in gene expression between wild type and Tgif1;Tgif2 double null mouse embryos at approximately 9.0 days after fertilization. Overall design: Stage matched individual mouse embryos at approximately 9.0 days after fertilization (~9-10 somites) were analyzed by RNA-seq. We analyzed four wild type embryos and eight conditional double mutant embryos, lacking both alleles of Tgif1 and both Tgif2 alleles.
Tgif1 and Tgif2 Repress Expression of the RabGAP Evi5l.
Age, Specimen part, Subject
View SamplesInflammatory mediators play a role in the pathogenesis/progression of chronic heart failure (CHF). The aim of the present study was to identify diagnostic/prognostic markers and gene expression profiles of CHF vs control.
Gene expression profiles in peripheral blood mononuclear cells of chronic heart failure patients.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis.
Specimen part, Cell line
View SamplesHuman lymphoid tissues harbor, in addition to CD56bright and CD56dim natural killer (NK) cells, a third NK cell population: CD69+CXCR6+ lymphoid tissue (lt)NK cells. The function and development of ltNK cells remain poorly understood. In this study we performed RNA sequencing on the CD56bright and CD56dim NK cells (from bone marrow and blood), and the ltNK cells (from bone marrow). In addition, the blood derived CD56dim, and bone marrow derived ltNK cells were further subdivided into a NKG2A+ and NKG2A- fraction. Paired blood and bone marrow samples of 4 healthy donors were included. When comparing the NKG2A fractions, only 3 genes (of 9382 genes included) had a significantly differential expression. Therefore, we pooled the expression data proportionally from the NKG2A+ and NKG2A- fractions in subsequent analyses. In ltNK cells, 1353 genes were differentially expressed compared to circulating NK cells. Several molecules involved in migration were downregulated in ltNK cells: S1PR1, SELPLG and CD62L. By flow cytometry we confirmed that the expression profile of adhesion molecules (CD49e-, CD29low, CD81high, CD62L-, CD11c-) and transcription factors (Eomeshigh, Tbetlow) of ltNK cells differed from their circulating counterparts. LtNK cells were characterized by enhanced expression of inhibitory receptors TIGIT and CD96 and low expression of DNAM1 and cytolytic molecules (GZMB, GZMH, GNLY). Their proliferative capacity was reduced compared to the circulating NK cells. By performing gene set enrichment analysis we identified DUSP6 and EGR2 as potential regulators of the ltNK cell transcriptome. Remarkably, comparison of the ltNK cell transcriptome to the published human spleen-resident memory CD8+ T (Trm) cell transcriptome revealed an overlapping gene signature. Moreover, the phenotypic profile of ltNK cells resembled that of CD8+ Trm cells in bone marrow. Together, we provide a comprehensive molecular framework of the conventional CD56bright and CD56dim NK cells as well as the tissue-resident ltNK cells and provide a core gene signature which might be involved in promoting tissue-residency. Overall design: mRNA sequencing of NK cell populations isolated from blood: CD56bright, NKG2A+ CD56dim and NKG2A- CD56dim, and bone marrow: CD56bright, CD56dim, NKG2A+ ltNK, and NKG2A- ltNK. Each sample has 4 biological replicates.
Human Bone Marrow-Resident Natural Killer Cells Have a Unique Transcriptional Profile and Resemble Resident Memory CD8<sup>+</sup> T Cells.
Specimen part, Subject
View SamplesEffect of the overexpression of the oncogenic form of the Vav2 protein in the NIH3T3 cell line under serum deprivation conditions. oncovav2-transformed NIH3T3 cells grown in serum-deprived medium (Vav2SD) are compared to the parental NIH3T3 controls under the same growth conditions (ContSD). Vav2SD cells are also compared to the oncovav2-transformed NIH3T3 cells growing exponentially and the NIH3T3 growing exponentially.
Microarray analysis of gene expression with age in individual nematodes.
Cell line
View SamplesDrosophila males double transcription of their single X chromosome to equalize X-linked gene expression with females, which carry two X chromosomes. Increased transcription requires the Male-Specific Lethal (MSL) complex. One of the primary functions of the MSL complex is thought to be enrichment of H4Ac16 on the male X chromosome, a modification linked to elevated transcription. The roX1 and roX2 RNAs are essential but redundant components of the MSL complex. Simultaneous removal of both roX RNAs reduces MSL X-localization and leads to ectopic binding of these proteins at autosomal sites and to the chromocenter. Some H4Ac16 accumulates at these ectopic sites in roX1- roX2- males, suggesting the possibility of increased expression. The global effect of roX mutations on gene expression was measured by microarray analysis. We found that expression of the X chromosome was decreased by 26% in roX1- roX2- male larvae, supporting the involvement of roX RNAs in the up-regulation of X-linked genes. This finding is broadly comparable to reports of reduced X chromosome expression following msl2 RNAi knockdown in S2 cells. In spite of strong MSL binding and H4Ac16 accumulation at autosomal sites in roX1- roX2- males, enhanced gene expression could not be detected at these sites by microarray analysis or reverse northern blotting. Thus, failure to compensate X-linked genes, rather than inappropriate up-regulation of autosomal genes at ectopic sites of MSL binding, appears to cause male lethality upon loss of roX RNAs.
roX RNAs are required for increased expression of X-linked genes in Drosophila melanogaster males.
Sex
View Sampleslet-7c and miR-294 were transfected into Dgcr8 -/- miRNA deficient ES cells and RNA was harvested after 12 hours
Opposing microRNA families regulate self-renewal in mouse embryonic stem cells.
Specimen part
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