Synovial biopsies were obtained from osteoarthritis (OA) synovium to find genes upregulated during OA.
Functional Tissue Analysis Reveals Successful Cryopreservation of Human Osteoarthritic Synovium.
Specimen part, Disease, Disease stage
View SamplesSynovial biopsies were obtained from rheumatoid arthritis (RA) synovium and from subjects without a joint disease to find gene upregulated during RA.
Disease-Regulated Gene Therapy with Anti-Inflammatory Interleukin-10 Under the Control of the CXCL10 Promoter for the Treatment of Rheumatoid Arthritis.
Disease, Disease stage
View SamplesBackground. Cellular senescence is a mechanism that virtually irreversibly suppresses the proliferative capacity of cells in response to various stress signals. This includes the expression of activated oncogenes, which cause Oncogene-Induced Senescence (OIS). A body of evidence points to the involvement of chromatin reorganization, including the formation of senescence-associated heterochromatic foci (SAHF). The nuclear lamina (NL) is an important contributor to genome organization and has been involved in cellular senescence and organismal aging. It interacts with multiple regions of the genome called lamina-associated domains (LADs). Some LADs are cell type-specific, while others are conserved between cell types and are referred to as constitutive LADs. Here, we used DamID to investigate the changes in genome-NL interactions in a model of OIS triggered by the expression of the BRAFV600E oncogene.Results. We found that OIS cells lose most of their constitutive LADs (cLADS), suggesting the loss of a specific mechanism that targets cLADs to the NL. In addition, multiple genes relocated to the NL. Unexpectedly, they were not repressed, implying the abrogation of the repressive activity of the NL during OIS. Finally, OIS cells displayed an increased association of telomeres with the NL.Conclusions. Our study reveals that senescent cells acquire a new type of LAD organization and suggest the existence of as yet unknown mechanisms that tether cLADs to the NL and repress gene expression at the NL.
Massive reshaping of genome-nuclear lamina interactions during oncogene-induced senescence.
Specimen part, Cell line, Subject, Time
View SamplesGene expression information is useful in prioritizing candidate genes in linkage intervals. The data can also identify pathways involved in the pathophysiology of disease.
Integration of expression profiles and genetic mapping data to identify candidate genes in intracranial aneurysm.
Sex, Age, Specimen part, Race
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The male germ cell gene regulator CTCFL is functionally different from CTCF and binds CTCF-like consensus sites in a nucleosome composition-dependent manner.
Specimen part
View SamplesThe effect of CTCFL mutation on the transcriptional program in testes
The male germ cell gene regulator CTCFL is functionally different from CTCF and binds CTCF-like consensus sites in a nucleosome composition-dependent manner.
Specimen part
View SamplesCTCFL binding to DNA and the effect of CTCFL expression in ES cells
The male germ cell gene regulator CTCFL is functionally different from CTCF and binds CTCF-like consensus sites in a nucleosome composition-dependent manner.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide analysis shows that Ldb1 controls essential hematopoietic genes/pathways in mouse early development and reveals novel players in hematopoiesis.
Specimen part
View SamplesThe first site exhibiting hematopoietic activity in mammalian development is the yolk sac blood island, which originates from the hemangioblast. Here we performed differentiation assays, as well as genome-wide molecular and functional studies in BL-CFCs to gain insight into the function of the essential Ldb1 factor in early primitive hematopoietic development. We show that the previously reported lack of yolk sac hematopoiesis and vascular development in Ldb1-/- mouse result from a decreased number of hemangioblasts and a block in their ability to differentiate into erythroid and endothelial progenitor cells. Transcriptome analysis and correlation with the genome wide binding pattern of Ldb1 in hemangioblasts revealed a number of direct target genes and pathways misregulated in the absence of Ldb1. The regulation of essential developmental factors by Ldb1 defines it as an upstream transcriptional regulator of hematopoietic/endothelial development. We show the complex interplay that exists between transcription factors and signaling pathways during the very early stages of hematopoietic/endothelial development and the specific signalling occurring in hemangioblasts in contrast to more advanced hematopoietic developmental stages. Finally, by revealing novel genes and pathways, not previously associated with early development, our study provides novel candidate targets to manipulate the differentiation of hematopoietic and/or endothelial cells.
Genome-wide analysis shows that Ldb1 controls essential hematopoietic genes/pathways in mouse early development and reveals novel players in hematopoiesis.
Specimen part
View SamplesIntroduction: In the recently completed Dutch GLUCOLD study, treatment of COPD patients with fluticasone salmeterol reduced the rate of decline in FEV1. These results indicate that ICS can have therapeutic efficacy in COPD. Aim: To explore the molecular mechanisms by which ICS exert their effects, we performed genome-wide gene expression profiling on bronchial biopsies from COPD patients who participated in the GLUCOLD study. Methods: An Affymetrix Human Gene Array ST version 1.0 was performed in a total of 221 bronchial biopsies that were available from 90 COPD patients at baseline and after 6 and 30 months of therapy. Linear mixed effects modeling was used to analyze treatment-specific changes in gene expression. A validation set was included and pathway analysis was performed with Gene Set Enrichment Analysis (GSEA). Results: The expression of 138 genes significantly decreased after both 6 and 30 months of treatment with fluticasone salmeterol versus placebo, whereas the expression of 140 genes increased. A more pronounced treatment-induced change in expression of 51 of these 278 genes was associated with a slower rate of decline in FEV1. Genes that decreased with treatment were involved in pathways related to cell cycle, oxidative phosphorylation, epithelial cell signaling, p53 signaling and T cell signaling. Genes that increased with treatment were involved in pathways related to focal adhesion, gap junction and extracellular matrix deposition. Conclusion: The present study suggests that gene expression in biological pathways of COPD is dynamic with treatment and reflects disease activity. This study opens the gate to targeted and phenotype-driven therapy of COPD.
Airway gene expression in COPD is dynamic with inhaled corticosteroid treatment and reflects biological pathways associated with disease activity.
Age
View Samples