Transcription profiling of human T Cell and monocyte populations, leukocyte or leukocyte subpopulations and skeletal muscle
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: IDDC Inflammation the Host Response to Injury
PROVIDER: E-GEOD-2328 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Application of genome-wide expression analysis to human health and disease.
Cobb J Perren JP Mindrinos Michael N MN Miller-Graziano Carol C Calvano Steve E SE Baker Henry V HV Xiao Wenzhong W Laudanski Krzysztof K Brownstein Bernard H BH Elson Constance M CM Hayden Douglas L DL Herndon David N DN Lowry Stephen F SF Maier Ronald V RV Schoenfeld David A DA Moldawer Lyle L LL Davis Ronald W RW Tompkins Ronald G RG Baker Henry V HV Bankey Paul P Billiar Timothy T Brownstein Bernard H BH Calvano Steve E SE Camp David D Chaudry Irshad I Cobb J Perren JP Davis Ronald W RW Elson Constance M CM Freeman Bradley B Gamelli Richard R Gibran Nicole N Harbrecht Brian B Hayden Douglas L DL Heagy Wyrta W Heimbach David D Herndon David N DN Horton Jureta J Hunt John J Laudanski Krzysztof K Lederer James J Lowry Stephen F SF Maier Ronald V RV Mannick John J McKinley Bruce B Miller-Graziano Carol C Mindrinos Michael N MN Minei Joseph J Moldawer Lyle L LL Moore Ernest E Moore Frederick F Munford Robert R Nathens Avery A O'keefe Grant G Purdue Gary G Rahme Laurence L Remick Daniel D Sailors Matthew M Schoenfeld David A DA Shapiro Michael M Silver Geoffrey G Smith Richard R Stephanopoulos Gregory G Stormo Gary G Tompkins Ronald G RG Toner Mehmet M Warren Shaw S West Michael M Wolfe Steven S Xiao Wenzhong W Young Vernon V
Proceedings of the National Academy of Sciences of the United States of America 20050321 13
The application of genome-wide expression analysis to a large-scale, multicentered program in critically ill patients poses a number of theoretical and technical challenges. We describe here an analytical and organizational approach to a systematic evaluation of the variance associated with genome-wide expression analysis specifically tailored to study human disease. We analyzed sources of variance in genome-wide expression analyses performed with commercial oligonucleotide arrays. In addition, ...[more]
Similar Datasets
Project description:expression files supporting: Application of genome-wide expression analysis to human health and disease. PNAS Supplementary Information: http://www.gluegrant.org/pubsupport/PNAS_1/ Keywords = clinical studies Keywords = gene expression Keywords = inflammation Keywords = microarray Keywords = trauma Keywords: other
2005-02-24 | GSE2328 | GEO
Project description:Major efforts are invested in the analysis of phenotypic variation in a population of individuals. While many of these studies focus on the genetic basis of phenotypic variation via measurements of DNA polymorphic sites, the environmental effects are still elusive. Here we propose a methodology, called CCCE ('Cell Composition Common Environment'), to identify environmental effects on the composition of immune cell functionalities. Specifically, CCCE is focused on the common experiences that are shared between siblings (the 'common environment'), designed to correct for cell subpopulation heterogeneity, and is based on a multicolor flow cytometry analysis across a large cohort of human monozygotic and dizygotic twins. We demonstrate that the CCCE methodology can provide insights on the relations between common environmental effects and the heterogenic functions of several immune cell types, such as NK cells effector functions and coagulation-related capabilities of monocytes. The software described in this article is available at http://csgi.tau.ac.il/CCCE.
| S-EPMC5915319 | biostudies-literature
Project description:BACKGROUND:Neonate immune cell functions lack full protection against pathogens. This could be either defect or protective mechanism against overshooting proinflammatory immune responses. We here analysed the function of classical, pro- and anti-inflammatory monocytes and granulocytes from neonates in comparison with adults to investigate if suppressed functions of subpopulations are causative for the unique neonatal immune status. Therefore, reactive oxygen species (ROS) and surface activation markers were quantified in subpopulations. METHODS:In a prospective, longitudinal study granulocyte and monocyte subpopulations were analysed in healthy term infants (>?37?week; n =?13) in comparison with healthy young adults (n =?11). Percentage (%) of cells expressing surface marker (HLA-DR, CD11b, CD62L, CD32, Toll-Like-Receptor-2) and expression per cell, determined by mean fluorescence intensity (MFI), were measured by flow cytometry. ROS production was induced by fMLP, PMA and E. coli in term neonates (>?37?week; n =?13). RESULTS:Classical granulocytes were down- and proinflammatory granulocytes upregulated in neonates compared with adults. Percentage of TLR-2 expressing granulocytes was increased in neonates. Granulocytic ROS production depended on stimulation. The percentage of anti-inflammatory monocytes was increased, while classical monocytes were reduced in neonates. HLA-DR (%, MFI) showed reduction for all monocyte subpopulations, while CD32, CD11b, CD62L and TLR-2 were differently regulated in comparison with adults. CONCLUSIONS:Differentially regulated granulocyte and monocyte subpopulations indicate a unique state of neonatal immunity to fight infections and prevent dysregulation. Further studies are needed to investigate the role of reduced granulocytic ROS formation and reduced monocytic HLA-DR in active disease.
| S-EPMC6884604 | biostudies-literature
Project description:The progressive accumulation of monocyte-derived cells in the atherosclerotic plaque is a hallmark of atherosclerosis. However, it is now appreciated that monocytes represent a heterogeneous circulating population of cells that differ in functionality. New approaches are needed to investigate the role of monocyte subpopulations in atherosclerosis since a detailed understanding of their differential mobilization, recruitment, survival and emigration during atherogenesis is of particular importance for development of successful therapeutic strategies. We present a novel methodology for the in vivo examination of monocyte subpopulations in mouse models of atherosclerosis. This approach combines cellular labeling by fluorescent beads with multiphoton microscopy to visualize and monitor monocyte subpopulations in living animals. First, we show that multiphoton microscopy is an accurate and timesaving technique to analyze monocyte subpopulation trafficking and localization in plaques in excised tissues. Next, we demonstrate that multiphoton microscopy can be used to monitor monocyte subpopulation trafficking in atherosclerotic plaques in living animals. This novel methodology should have broad applications and facilitate new insights into the pathogenesis of atherosclerosis and other inflammatory diseases.
| S-EPMC3443108 | biostudies-literature
Project description:In vivo studies in mice have identified subsets of monocytes involved in the inflammatory response to pathogens, but their respective functions remains poorly understood. We report that human CD14+ monocytes represent functional ortholog to mouse Ly6C+ monocytes and are responsible for phagocytosis, Reactive Oxygen Species (ROS) and cytokine production in response to a broad range of pathogen associated molecular patterns (PAMP). In contrast a discrete population of CD14dim cells are ortholog to the mouse ly6C- monocytes and share their ability to patrol the endothelium of blood vessels, but do not produce ROS, are weak phagocytes, and poorly respond to bacterial PAMPs. Instead, CD14dim monocytes are critical for production of pro-apoptotic and pro-inflammatory cytokines in response to viruses and nucleic acids via a unique TLR7-8/MyD88/MEK pathway, while they may also contribute to tissue damage in autoimmune diseases such as Lupus.
2011-01-07 | E-MEXP-2544 | biostudies-arrayexpress
Project description:Spondyloarthropathies (SpA) are a family of rheumatic disorders that could be divided into axial (axSpA) and peripheral (perSpA) sub-forms depending on the disease clinical presentation. The chronic inflammation is believed to be driven by innate immune cells such as monocytes, rather than self-reactive cells of adaptive immune system. The aim of the study was to investigate the micro-RNA (miRNA) profiles in monocyte subpopulations (classical, intermediate and non-classical subpopulations) acquired from SpA patients or healthy individuals in search for prospective disease specific and/or disease subtype differentiating miRNA markers. Several SpA-specific and axSpA/perSpA differentiating miRNAs have been identified that appear to be characteristic for specific monocyte subpopulation. For classical monocytes, upregulation of miR-567 and miR-943 was found to be SpA-specific, whereas downregulation of miR-1262 could serve as axSpA-differentiating, and the expression pattern of miR-23a, miR-34c, mi-591 and miR-630 as perSpA-differentiating markers. For intermediate monocytes, expression levels of miR-103, miR-125b, miR-140, miR-374, miR-376c and miR-1249 could be used to distinguish SpA patients from healthy donors, whereas the expression pattern of miR-155 was identified as characteristic for perSpA. For non-classical monocytes, differential expression of miR-195 was recognized as general SpA indicator, while upregulation of miR-454 and miR-487b could serve as axSpA-differentiating, and miR-1291 as perSpA-differentiating markers. Our data indicate for the first time that in different SpA subtypes, monocyte subpopulations bear disease-specific miRNA signatures that could be relevant for SpA diagnosis/differentiation process and may help to understand SpA etiopathology in the context of already known functions of monocyte subpopulations.
| S-EPMC10149963 | biostudies-literature
Project description:The aim of this study was to identify cell-type specific contributions to the acute HIV transcriptional signature identified in the CHAVI 001 acute 32 prospective cohort.
2016-02-15 | GSE25669 | GEO
Project description:Prenatal arsenic exposure is associated with increased risk of disease in adulthood. This has led to considerable interest in arsenic's ability to disrupt fetal programming. Many studies report that arsenic exposure alters DNA methylation in whole blood but these studies did not adjust for cell mixture. In this study, we examined the relationship between arsenic in maternal drinking water collected ? 16 weeks gestational age and DNA methylation in cord blood (n = 44) adjusting for leukocyte-tagged differentially methylated regions. DNA methylation was quantified using the Infinium HumanMethylation 450 BeadChip array. Recursively partitioned mixture modeling examined the relationship between arsenic and methylation at 473,844 CpG sites. Median arsenic concentration in water was 12 µg/L (range<1- 510 µg/L). Log 10 arsenic was associated with altered DNA methylation across the epigenome (P = 0.002); however, adjusting for leukocyte distributions attenuated this association (P = 0.013). We also observed that arsenic had a strong effect on the distribution of leukocytes in cord blood. In adjusted models, every log 10 increase in maternal drinking water arsenic exposure was estimated to increase CD8+ T cells by 7.4% (P = 0.0004) and decrease in CD4+ T cells by 9.2% (P = 0.0002). These results show that prenatal exposure to arsenic had an exposure-dependent effect on specific T cell subpopulations in cord blood and altered DNA methylation in cord blood. Future research is needed to determine if these small changes in DNA methylation alter gene expression or are associated with adverse health effects.
| S-EPMC4063836 | biostudies-literature
Project description:BackgroundThe in vitro pharmacology of baricitinib, upadacitinib, and tofacitinib was evaluated to understand differences among these JAK inhibitors (JAKis) at the cellular level.MethodsPeripheral blood mononuclear cells from healthy donors were incubated with different JAKis, levels of phosphorylated signal transducer and activator of transcription (pSTAT) were measured following cytokine stimulation, and half maximum inhibitory concentration (IC50) values were calculated in phenotypically gated leukocyte subpopulations. Therapeutic dose relevance of the in vitro analysis was assessed using calculated mean concentration-time profiles over 24?h obtained from JAKi-treated subjects. Time above IC50 and average daily percent inhibition of pSTAT formation were calculated for each JAKi, cytokine, and cell type.ResultsDistinct JAKis displayed different in vitro pharmacologic profiles. For example, tofacitinib and upadacitinib were the most potent inhibitors of the JAK1/3-dependent cytokines tested (interleukin [IL]-2, IL-4, IL-15, and IL-21) with lower IC50 values and increased time above IC50 translating to a greater overall inhibition of STAT signaling during the dosing interval. All JAKis tested inhibited JAK1/2-dependent cytokines (e.g., IL-6 and interferon [IFN]-?), the JAK1/tyrosine kinase 2 (TYK2)-dependent cytokines IL-10 and IFN-?, the JAK2/2-dependent cytokines IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF), and the JAK2/TYK2-dependent cytokine granulocyte colony-stimulating factor (G-CSF), but often to significantly differing degrees.ConclusionsDifferent JAKis modulated distinct cytokine pathways to varying degrees, and no agent potently or continuously inhibited an individual cytokine signaling pathway throughout the dosing interval. Notably, baricitinib inhibited JAK1/3 signaling to a lesser extent than upadacitinib and tofacitinib, while upadacitinib, baricitinib, and tofacitinib inhibited the signaling of JAK2/2-dependent cytokines, including GM-CSF and IL-3, as well as the signaling of the JAK2/TYK2-dependent cytokine G-CSF.
| S-EPMC6679539 | biostudies-literature
Project description:AIM:The subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria in skeletal muscle appear to have distinct biochemical properties affecting metabolism in health and disease. The isolation of mitochondrial subpopulations has been a long-time challenge while the presence of a continuous mitochondrial reticulum challenges the view of distinctive SSM and IFM bioenergetics. Here, a comprehensive approach is developed to identify the best conditions to separate mitochondrial fractions. METHODS:The main modifications to the protocol to isolate SSM and IFM from rat skeletal muscle were: (a) decreased dispase content and homogenization speed; (b) trypsin treatment of SSM fractions; (c) recentrifugation of mitochondrial fractions at low speed to remove subcellular components. To identify the conditions preserving mitochondrial function, integrity, and maximizing their recovery, microscopy (light and electron) were used to monitor effectiveness and efficiency in separating mitochondrial subpopulations while respiratory and enzyme activities were employed to evaluate function, recovery, and integrity. RESULTS:With the modifications described, the total mitochondrial yield increased with a recovery of 80% of mitochondria contained in the original skeletal muscle sample. The difference between SSM and IFM oxidative capacity (10%) with complex-I substrate was significant only with a saturated ADP concentration. The inner and outer membrane damage for both subpopulations was <1% and 8%, respectively, while the respiratory control ratio was 16. CONCLUSION:Using a multidisciplinary approach, conditions were identified to maximize SSM and IFM recovery while preserving mitochondrial integrity, biochemistry, and morphology. High quality and recovery of mitochondrial subpopulations allow to study the relationship between these organelles and disease.
| S-EPMC6335164 | biostudies-literature