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TET1 is a maintenance DNA demethylase that prevents methylation spreading in differentiated cells.
Cell line
View SamplesWe report that full length TET1 (TET1-FL) overexpression fails to induce global DNA demethylation in HEK293T cells. The preferential binding of TET1-FL to hypomethylated CpG islands (CGIs) through its CXXC domain leads to its inhibited 5-hydroxymethylcytosine (5hmC) production as methylation level increases. TET1-FL-induced 5hmC accumulates at CGI edges, while TET1 knockdown induces methylation spreading from methylated edges into hypomethylated CGIs. However, TET1 can regulate gene transcription independent of its dioxygenase catalytic function. Thus, our results identify TET1 as a maintenance DNA demethylase that does not purposely decrease methylation levels, but specifically maintains the DNA hypomethylation state of CGIs in adult cells.
TET1 is a maintenance DNA demethylase that prevents methylation spreading in differentiated cells.
Cell line
View SamplesTREM-1 is an orphan immunoreceptor expressed on monocytes, macrophages, and neutrophils. TREM-1 associates with and signals via the adapter protein DAP12/TYROBP, which contains an immunoreceptor tyrosine-based activation motif (ITAM). TREM-1 activation by receptor cross-linking is pro-inflammatory, and can amplify cellular responses to Toll-like receptor (TLR) ligands such as bacterial lipopolysaccharide (LPS). To investigate the cellular consequences of TREM-1 activation, we have characterized global gene expression changes in human monocytes in response to TREM-1 cross-linking in comparison to and combined with LPS. Both TREM-1 activation and LPS up-regulate chemokines, cytokines, matrix metalloproteases, and PTGS/COX2, consistent with a core inflammatory response. However, other immunomodulatory factors are selectively induced, including SPP1 and CSF1 (i.e., M-CSF) by TREM-1 activation and IL-23 and CSF3 (i.e., G-CSF) by LPS. Additionally, cross-talk between TREM-1 activation and LPS occurs on multiple levels. While synergy in GM-CSF protein production is reflected in commensurate mRNA abundance, comparable synergy in IL-1b protein production is not. TREM-1 activation also attenuates the induction of some LPS target genes, including those that encode IL-12 cytokine family subunits. Whereas positive TREM-1 outputs are abolished by the PI3K inhibitor wortmannin, this attenuation is largely PI3K-independent. These experiments provide a detailed analysis of the cellular consequences of TREM-1 activation, and highlight some of the complexity in signal integration between ITAM- and TLR-mediated signaling.
Innate immune responses to TREM-1 activation: overlap, divergence, and positive and negative cross-talk with bacterial lipopolysaccharide.
No sample metadata fields
View SamplesChronic tendon injuries, also known as tendinopathy, are common among professional and recreational athletes. These injuries result in a significant amount of morbidity and health care expenditure and yet little is known about the molecular mechanism leading to tendinopathy. We have used histological evaluation and molecular profiling to determine the gene expression changes in 23 human patients undergoing surgical procedures for the treatment of chronic tendinopathy. Diseased tendons have altered extracellular matrix, fiber disorientation, increased cellular content and vasculature and the absence of inflammatory cells. Global gene expression profiling identified 1783 transcripts with significant different expression patterns in the diseased tendons. Global pathway analysis further suggests altered expression of extracellular matrix proteins and the lack of an appreciable inflammatory response. We have identified pathways and genes regulated in tendinopathy samples that will help contribute to the understanding of the disease towards the development of novel therapeutics.
Regulation of gene expression in human tendinopathy.
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesEvaluation of differential expression between CLL patients in a chemoimmunotherapy trial with age-matched controls
LEF-1 is a prosurvival factor in chronic lymphocytic leukemia and is expressed in the preleukemic state of monoclonal B-cell lymphocytosis.
Specimen part, Disease, Disease stage
View SamplesMammalian spermatogenesis is a complex biological process that occurs within a highly organized tissue, the seminiferous epithelium. The coordinated maturation of spermatogonia, spermatocytes and spermatids suggests the existence of precise programs of gene expression in these cells as well as in their neighboring somatic Sertoli cells. The objective of this study was to elucidate genes encoding the proteins that execute these programs. Rat seminiferous tubules at stages I, II-III, IV-V, VI, VIIa,b, VIIc,d, VIII, IX-XI, XII, XIII-XIV of the cycle were isolated by microdissection and Sertoli cells, spermatogonia plus early spermatocytes, pachytene spermatocytes and spermatids were purified from enzymatically-dispersed testes. Microarray analysis using Rat Genome 230 2.0 arrays identified a total of 16,971 probe sets that recognized transcripts. A comparison with the transcriptome of other tissues identified 398 testis-specific probe sets, which therefore are potential targets for the development of new contraceptives. Sequential waves of cell and stage-specific gene expression are associated with progression of germ cells through the stages of the cycle of the seminiferous epithelium and 1612 probe sets recognized transcripts whose expressions varied at least 4-fold across the stages of the cycle. Pathway analyses reveal that entire biological processes are regulated cyclically in testicular cells. Important among these are cell cycle and DNA repair. Thus, stage-specific gene expression is a widespread and fundamental characteristic of spermatogenic cells and Sertoli cells.
Stage-specific gene expression is a fundamental characteristic of rat spermatogenic cells and Sertoli cells.
No sample metadata fields
View SamplesIn the present study, microarray analysis was performed on RNA isolated from purified SLCs, PLCs, ILCs, ALCs and bone stem cells, using Affymetrix Rat Genome RAE230 2.0 arrays which monitor ~30,000 transcripts from over ~28,000 well-substantiated genes. The focus is on the differences and similarities between SLCs and bone stem cells, and between SLCs and PLCs, ILCs and ALCs
Stem Leydig cell differentiation: gene expression during development of the adult rat population of Leydig cells.
Specimen part
View SamplesRNA-seq was performed after MCF7 cells were treated with S2101, UNC0638, GSK343, depsipeptide alone or in combination with decitabine Overall design: Biological triplicates were performed for a total of 30 samples. Fold change of each gene was calculated by comparing change in expression after inhibitor treatment to expression in the control samples
Transcriptional Selectivity of Epigenetic Therapy in Cancer.
No sample metadata fields
View SamplesRNA-seq was performed after HL60 cells were treated with S2101, UNC0638, GSK343, depsipeptide alone or in combination with decitabine Overall design: Biological triplicates were performed for a total of 30 samples. Fold change of each gene was calculated by comparing change in expression after inhibitor treatment to expression in the control samples
Transcriptional Selectivity of Epigenetic Therapy in Cancer.
No sample metadata fields
View SamplesRNA-seq was performed after YB5 cells were treated with S2101, UNC0638, GSK343, depsipeptide alone or in combination with decitabine Overall design: Biological triplicates were performed for a total of 30 samples. Fold change of each gene was calculated by comparing change in expression after inhibitor treatment to expression in the control samples
Transcriptional Selectivity of Epigenetic Therapy in Cancer.
No sample metadata fields
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