063dc665-788d-4a77-9942-71b0f71585bd - samples
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ABSTRACT:
PROVIDER: EGAD00001010879 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:DNA methylation has an impact on regulation of gene expression, however the relation between the two is complex. By performing an integrative analysis of the methylome and transcriptome of the four main circulating immune cell-subsets from healthy females, namely B cells, monocytes, CD4 and CD8 T cells, the relation between the two was characterized. In addition, in light of the known sex bias in the prevalence of several immune-mediated diseases, the female datasets were compared with similar public available male datasets. Immune subset-specific differentially methylated regions (DMRs) were found to be highly similar between males and females; however numerous sex-specific DMRs shared by the four leukocytes subsets were identified, most located on autosomal chromosomes. This provides a list of highly interesting candidate genes to be studied in diseases with sexual dimorphism like autoimmunity. Immune cell-specific DMRs were mainly located in the gene body and intergenic region, distant from CpG islands but overlapping with enhancer elements, thus indicating the importance of distal regulatory elements in leukocyte subsets. In contrast; sex-specific DMRs were over-represented in CpG islands, suggesting some difference in regulation between sex and immune-cell specificity. Both positive and negative correlations between cell-specific expression and methylation were observed, with negative correlation being more frequent. Our acquired immune cell- and sex- specific methylome and transcriptome profiles provide novel insight on their complex regulatory interactions, and may particularly contribute to research of immune-mediated diseases. DNA purified from isolated 5 cell subsets (monocyte, B cells, CD4 T cells, CD8 T cells and PBMCs) obtained from 6 healthy female donors
2016-07-01 | E-GEOD-71244 | biostudies-arrayexpress
Project description:DNA methylation has an impact on regulation of gene expression, however the relation between the two is complex. By performing an integrative analysis of the methylome and transcriptome of the four main circulating immune cell-subsets from healthy females, namely B cells, monocytes, CD4 and CD8 T cells, the relation between the two was characterized. In addition, in light of the known sex bias in the prevalence of several immune-mediated diseases, the female datasets were compared with similar public available male datasets. Immune subset-specific differentially methylated regions (DMRs) were found to be highly similar between males and females; however numerous sex-specific DMRs shared by the four leukocytes subsets were identified, most located on autosomal chromosomes. This provides a list of highly interesting candidate genes to be studied in diseases with sexual dimorphism like autoimmunity. Immune cell-specific DMRs were mainly located in the gene body and intergenic region, distant from CpG islands but overlapping with enhancer elements, thus indicating the importance of distal regulatory elements in leukocyte subsets. In contrast; sex-specific DMRs were over-represented in CpG islands, suggesting some difference in regulation between sex and immune-cell specificity. Both positive and negative correlations between cell-specific expression and methylation were observed, with negative correlation being more frequent. Our acquired immune cell- and sex- specific methylome and transcriptome profiles provide novel insight on their complex regulatory interactions, and may particularly contribute to research of immune-mediated diseases. RNA purified from isolated 5 cell subsets (monocyte, B cells, CD4 T cells, CD8 T cells and PBMCs) obtained from 6 healthy female donors
2016-07-01 | E-GEOD-71115 | biostudies-arrayexpress
Project description:Multiple sclerosis is an immune mediated disease of the central nervous system. High-dose immunosuppression therapy followed by autologous hematopoietic stem cell transplantation (HDI/AHSCT) has emerged in the past few years as a new treatment strategy in patients with severe MS and refractory to conventional treatment. We characterized the molecular profile of T cells during immune reconstitution of these patients. Total RNA of CD4+ and CD8+ T cells from eight MS patients before transplantation and four patients at 6 months, 1 and 2 years after transplantation was processed for DNA microarray analysis. We investigated the molecular and biological function of DEG using bioinformatics tools and selected genes involved with immune response to measure quantitative gene expression by Real-time PCR. In CD8+ T cells, we measured the levels of expression of 23 genes modulated after transplantation: nine transcriptional factors (LEF1, FOXD1, CEBPD, JUN, JUNB, RELB, IFI16, AEBP1) including the translational factor PDCD4, the chemokine CCR7 and adhesion molecule L Selectin, three TNF superfamily members (TNFRSF4, TNFRSF19L, LT?), seven genes involved with molecular signaling (SOCS1, SOCS3, DGKH, CSNK1L1, IKB?, IKB?, IKB?), and the immune cell receptors CD47 and SIRPG. In CD4+ T cells, we evaluated the relative level of expression of STAT3, FcRL3, PDCD1, DGKH, CSNK1L1, L Selectin, CCR7 and PIAS3 that were all modulated after transplantation. We found significantly transcriptional changes in both T cells subsets during the first 2 years post-transplantation, but the analysis of CD8+ T cells revealed more extensive changes of genes involved in effector immune responses. In order to study the transcriptional changes in T cell subsets from MS patients submitted HID/HSCT, immunomagnetically purified CD4+ and CD8+ T-cells from the peripheral blood of 8 patients before transplantation and 4 patients 6 months, 1 year and 2 years after tranplantation, as well as from 4 healthy controls were isolated and processed the microarray assay according Agilent's protocol. The differential expressed genes, molecular characterization and networks analysis were evaluated using robust bioinformatic tools, then the real time PCR was done to validate the 27 immune related-genes.
2011-11-03 | E-GEOD-32988 | biostudies-arrayexpress
Project description:Background: Dendritic cells (DCs) are critical for regulating CD4 and CD8 T cell immunity, controlling Th1, Th2, and Th17 bias, generating inducible Tregs, and inducing tolerance. Multiple DC subsets have been identified in the mouse that are thought to have evolved to control these different immune outcomes. However, how these subsets differentially respond to inflammatory and/or tolerogenic signals in order to accomplish their divergent functionality remains unclear. Results: We analysed the responses of murine, splenic CD8 and CD11b DC subsets to in-vivo stimulation with lipopolysaccharide using RNA-Seq and systems biology approaches and observed responses are highly subset-specific. We reanalysed multiple datasets from the literature and show that these subset responses are obscured when analysing signaling at the population level. We show that the subset-specificity is due to the unique regulation of distinct TLR4 pathway modulators that ‘fine-tune’ a common TLR4 cascade rather and not due to major differences in signaling pathways or transcription factors. Conclusions: We propose the Pathway Modulation Model wherein common signaling pathways are regulated by unique sets of modulators allowing for distinct immune responses in closely related DC subsets. We extend these observations using analagous datasets from the literature and show that our model provides a global mechanism for generating cell subset-specific signaling in multiple subpopulations in mouse and man. Splenic CD8 and CD11b DC subsets from LPS stimulated (10 pooled animals) and Control (5 pooled animals) mice were analysed by RNA-Seq.
2014-07-01 | E-GEOD-42573 | biostudies-arrayexpress
Project description:Vitamin D deficiency is a risk factor for developing multiple sclerosis (MS). However, the immune effects of vitamin D in people with MS are not well understood. We analyzed transcriptomic datasets generated by RNA sequencing of immune cell subsets (CD4+, CD8+ T cells, B cells, monocytes) from 33 healthy controls and 33 untreated MS cases. We utilized a traditional bioinformatic pipeline and weighted gene co-expression network analysis (WGCNA) to determine genes and pathways correlated with endogenous vitamin D. In controls, CD4+ and CD8+ T cells had 1079 and 1188 genes, respectively, whose expressions were correlated with plasma 25-hydroxyvitamin D level (P<0.05). Functional enrichment analysis identified association with TNF-alpha and MAPK signaling. In CD4+ T cells of controls, vitamin D level was associated with expression levels of several genes proximal to multiple sclerosis risk loci (P=0.01). Genes differentially associated with endogenous vitamin D by case-control status were enriched in TNF-alpha signaling via NF-κB. WGCNA suggested a blunted response to vitamin D in cases relative to controls. Collectively, our findings provide further evidence for the immune effects of vitamin D, and demonstrate a differential immune response to vitamin D in cases relative to controls, highlighting a possible mechanism contributing to MS pathophysiology.
| EGAS00001007254 | EGA
Project description:This study compared whole transcriptome signatures of 6 immune cell subsets and whole blood from patients with an array of immune-associated diseases. Fresh blood samples were collected from healthy subjects and subjects diagnosed type 1 diabetes, amyotrophic lateral sclerosis, and sepsis, as well as multiple sclerosis patients before and 24 hours after the first treatment with IFN-beta. At the time of blood draw, an aliquot of whole blood was collected into a Tempus tube (Invitrogen), while the remainder of the primary fresh blood sample was processed to highly pure populations of neutrophils, monocytes, B cells, CD4 T cells, CD8 T cells, and natural killer cells. RNA was extracted from each of these cell subsets, as well as the whole blood samples, and processed into RNA sequencing (RNAseq) libraries (Illumina TruSeq). Sequencing libraries were analyzed on an Illumina HiScan, with a target read depth of ~20M reads. Reads were demultiplexed, mapped to human gene models (ENSEMBL), and tabulated using HTSeq. Read count data were normalized by the TMM procedure (edgeR package). We performed whole genome RNAseq profiling of immune cell subsets and whole blood from subjects with an array of immune-associated diseases.
2015-01-06 | E-GEOD-60424 | biostudies-arrayexpress
Project description:Dendritic cells (DCs) are critical in mediating immunity to pathogens, vaccines, tumors and tolerance to self. Significant progress has been made in the study of DC subsets in murine models but the translation of these findings to human DC immunobiology has not been fully realized. Murine splenic CD8+ DC and CD103+ DC possess potent antigen cross-presenting capacity. Although recent evidence points to human blood CD141+ DCs as the functional equivalent of CD8+ DC, the precise identity of the human migratory cross-presenting DC has remained elusive. We performed phenotypic and functional analyses to interrogate the DC compartment of human non-lymphoid tissues and identified three distinct subsets: i) CD141high DCs, ii) CD1c DCs and iii) CD14+ DCs. Only CD141high DCs were capable of cross-presenting soluble antigen. Comparative transcriptome analysis of steady state monocyte and DC subsets between mouse and human confirmed conservation between species, aligning the following subsets together: i) human CD141high DCs with mouse CD8+ and CD103+ DCs, ii) human CD1c+ DCs with mouse CD4+ DCs and iii) human CD14+ DC with mouse monocyte subsets. The lack of positive association between human CD1c+ DCs and mouse non-lymphoid tissue CD11b+ DCs highlights heterogeneity and predicts the existence of a monocyte-like cell within the CD11b+ DCs. Gene expression analysis using total RNA from specific human and mouse monocyte and dendritic cell subsets purified by FACS.
2012-07-11 | E-GEOD-35457 | biostudies-arrayexpress
Project description:Dendritic cells (DCs) are critical in mediating immunity to pathogens, vaccines, tumors and tolerance to self. Significant progress has been made in the study of DC subsets in murine models but the translation of these findings to human DC immunobiology has not been fully realized. Murine splenic CD8+ DC and CD103+ DC possess potent antigen cross-presenting capacity. Although recent evidence points to human blood CD141+ DCs as the functional equivalent of CD8+ DC, the precise identity of the human migratory cross-presenting DC has remained elusive. We performed phenotypic and functional analyses to interrogate the DC compartment of human non-lymphoid tissues and identified three distinct subsets: i) CD141high DCs, ii) CD1c DCs and iii) CD14+ DCs. Only CD141high DCs were capable of cross-presenting soluble antigen. Comparative transcriptome analysis of steady state monocyte and DC subsets between mouse and human confirmed conservation between species, aligning the following subsets together: i) human CD141high DCs with mouse CD8+ and CD103+ DCs, ii) human CD1c+ DCs with mouse CD4+ DCs and iii) human CD14+ DC with mouse monocyte subsets. The lack of positive association between human CD1c+ DCs and mouse non-lymphoid tissue CD11b+ DCs highlights heterogeneity and predicts the existence of a monocyte-like cell within the CD11b+ DCs. Gene expression analysis using total RNA from specific human and mouse monocyte and dendritic cell subsets purified by FACS.
2012-07-11 | E-GEOD-35458 | biostudies-arrayexpress
Project description:The overall objective of this study was to characterize the diversity and ontogeny of CD8 T cells in untreated lung tumors. This was accomplished by performing bulk RNAseq and flow cytometry analysis on CD8+ T cell subsets isolated from tumor tissue, normal adjacent to tumor (juxta0 tissue samples from patients undergoing surgical resection for early-stage, untreated non-small-cell lung cancer (NSCLC).
2023-10-09 | GSE232899 | GEO
Project description:To test the chromatin accessibility of different immune cell subsets, we isolated CD4+T cells, CD8+T cells, CD19+B cells and CD14+ monocytes from human PBMCs and performed ATAC assay.
2020-11-05 | E-MTAB-8982 | biostudies-arrayexpress