Ontology highlight
ABSTRACT:
PROVIDER: PRJNA867683 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20989823_1.fastq.gz | Fastqsanger.gz | |||
| SRR20989823_2.fastq.gz | Fastqsanger.gz | |||
| SRR20989824_1.fastq.gz | Fastqsanger.gz | |||
| SRR20989824_2.fastq.gz | Fastqsanger.gz | |||
| SRR20989825_1.fastq.gz | Fastqsanger.gz |
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Project description:CD4(+)Foxp3(+) regulatory T (Treg) cells originate primarily from thymic differentiation, but conversion of mature T lymphocytes to Foxp3 positivity can be elicited by several means, including in vitro activation in the presence of TGF-beta. Retinoic acid (RA) increases TGF-beta-induced expression of Foxp3, through unknown molecular mechanisms. We showed here that, rather than enhancing TGF-beta signaling directly in naive CD4(+) T cells, RA negatively regulated an accompanying population of CD4(+) T cells with a CD44(hi) memory and effector phenotype. These memory cells actively inhibited the TGF-beta-induced conversion of naive CD4(+) T cells through the synthesis of a set of cytokines (IL-4, IL-21, IFN-gamma) whose expression was coordinately curtailed by RA. This indirect effect was evident in vivo and required the expression of the RA receptor alpha. Thus, cytokine-producing CD44(hi) cells actively restrain TGF-beta-mediated Foxp3 expression in naive T cells, and this balance can be shifted or fine-tuned by RA. All gene expression profiles were obtained from highly purified T cell populations sorted by flow cytometry. To reduce variability, cells from multiple mice were pooled for sorting, and replicates were generated for essentially all groups. RNA from 0.5-3 x 105 cells was amplified, labeled, and hybridized to Affymetrix M430v2 microarrays. Raw data were preprocessed with the RMA algorithm in GenePattern, and averaged expression values were used for analysis.
2008-11-16 | E-GEOD-13306 | biostudies-arrayexpress
Project description:CD4(+)Foxp3(+) regulatory T (Treg) cells originate primarily from thymic differentiation, but conversion of mature T lymphocytes to Foxp3 positivity can be elicited by several means, including in vitro activation in the presence of TGF-beta. Retinoic acid (RA) increases TGF-beta-induced expression of Foxp3, through unknown molecular mechanisms. We showed here that, rather than enhancing TGF-beta signaling directly in naive CD4(+) T cells, RA negatively regulated an accompanying population of CD4(+) T cells with a CD44(hi) memory and effector phenotype. These memory cells actively inhibited the TGF-beta-induced conversion of naive CD4(+) T cells through the synthesis of a set of cytokines (IL-4, IL-21, IFN-gamma) whose expression was coordinately curtailed by RA. This indirect effect was evident in vivo and required the expression of the RA receptor alpha. Thus, cytokine-producing CD44(hi) cells actively restrain TGF-beta-mediated Foxp3 expression in naive T cells, and this balance can be shifted or fine-tuned by RA.
2008-11-16 | GSE13306 | GEO
Project description:The presented data corresponds to the analysis of two discrete subsets of human CD8+ naive T cells, defined by positive and negative expression of the chemokine receptor CXCR3 (TNR3-, TNR3+). In this study we demonstrated that these subsets have different potential to generate fully-differentiated effector T cells following antigen-specific stimulation. The performed systematic immune repertoire analysis (T cell receptor beta chain (TRB)) of the sorted cell subsets revealed diverse physico-chemical properties of TRB CDR3 sequences suggesting enhanced TCR self-reactivity in human TNR3+ cells. In total, we analyzed 74 samples (from 11 patients, 3 replicates of each cell subset (excluding one missing replicate) and additionally for 3 patients CD8+ memory T cells in 3 replicates). We used the Human TCR Profiling Kit (MiLaboratory LLC) for sequencing libraries preparation and Illumina NextSeq 550 sequencing (150+150bp) followed by the demultiplexing procedure using MIGEC software (https://github.com/mikessh/migec).
2019-10-17 | E-MTAB-7638 | biostudies-arrayexpress
Project description:Naive CD4+ T cells are the common precursors of multiple effector and memory T cell subsets and possess a high plasticity in terms of differentiation potential. This stem-cell like character is important for cell therapies aiming at regeneration of specific immunity. Cell surface proteins are crucial for recognition and response to signals mediated by other cells or environmental changes. Knowledge of cell surface proteins of human naive CD4+ T cells and their changes during the early phase of T cell activation is urgently needed for a guided differentiation of naive T cells and may support the selection of pluripotent cells for cell therapy.<br>Periodate oxidation and aniline-catalyzed oxime ligation (PAL) technology was applied with subsequent quantitative LC-MS/MS (PAL-qLC-MS/MS) to generate a dataset describing the surface proteome of human naive CD4+ T cells and to monitor dynamic changes during the early phase of activation. This led to the identification of 173 N-glycosylated surface proteins, of which 24 were previously not known to be expressed on human naive CD4+ T cells or have no defined role within T cell activation. To independently confirm the proteomic dataset and to analyse the cell surface by an alternative technique a systematic phenotypic expression analysis of surface antigens via flow cytometry was performed. This screening expanded the previous dataset, resulting in 229 surface proteins which are expressed on naive unstimulated and activated CD4+ T cells. Furthermore, we generated a surface expression atlas based on transcriptome data, experimental annotation and predicted subcellular localization, and correlated the proteomics result with this transcriptional dataset.<br>This extensive surface atlas provides an overall naive CD4+ T cell surface resource and will enable future studies aiming at a deeper understanding of mechanisms of T cell biology allowing the identification of novel immune targets usable for the development of therapeutic treatments.
2015-05-27 | PXD001432 | Pride
Project description:<p>We use next generation sequencing to investigate the different transcriptomes of closely related CD4+ T-cells from healthy human donors to elucidate the genetic programs that underlie their specialized immune functions. Six cell types were included: Regulatory T-cells (CD25hiCD127low/neg with >95% FOXP3+ purity), regulatory T-cells activated using PMA/ionomycin, CD25-CD45RA+ ('naive' helper T-cells), CD25-CD45RO+ ('memory' helper T-cells), activated Th17 cells (>98% IL17A+ purity) and activated IL17-CD4+ T-cells (called 'ThPI'). Poly-T capture beads were used to isolate mRNA from total RNA, and fragment sizes of ~200 were sequenced from both ends on Illumina's genome analyzer. We confirm many of the canonical signature genes of T-cell populations, but also discover new genes whose expression is limited to specific CD4 T-cell lineages, including long non-coding RNAs. Additionally, we find that genes encoded at loci linked to multiple human autoimmune diseases are enriched for preferential expression upon T-cell activation, suggesting that an aberrant response to T-cell activation is fundamental to pathogenesis.</p>
| phs000626 | dbGaP
Project description:Conventional CD4 and CD8 single positive T cell lineages constitute the main differentiation pathway in the thymus. In human thymus, a minor TCRαβ differentiation pathway diverges from the early double positive stage, consisting of CD10+ PD-1+ cells. These cells are phenotypically and functionally similar to murine agonist-selected intraepithelial T lymphocyte precursors (IELps) which home to the small intestine. Here, the progeny of the human agonist-selected IEL lineage was identified in antigen-inexperienced cord blood (CB) with a polyclonal T cell receptor (TCR) repertoire exhibiting a bias towards early TCR alpha chain rearrangements and elevated autoreactive indices. Single-cell RNA sequencing allowed further delineation of this unconventional lineage in CB. Trajectory analysis, along with TCR repertoire analysis, transcriptomics and proteomics, suggests a precursor-progeny relationship with the thymic IELps. The distinct, heterogeneous CB population can now be defined as CD3+ TCRαβ+ CD4- CCR7- CD26-. Besides recent thymic emigrants, this population also consists of newly identified effector clusters and previously described populations: the suppressive NK receptor expressing CD8+ Treg population, the KIR/NKG2A+ EOMES+ virtual memory population and the CD8αα+ T cell populations. The population shows a discriminating stable HELIOS expression and is exclusively able to downregulate CD8β expression, resulting in double negative T cells. The functional properties of this population suggest that the cells expand on inflammatory cues and exert cytotoxic and proinflammatory activity.
2023-02-10 | PXD033392 | Pride
Project description:Disturbed expression of microRNAs (miRNAs) in regulatory T-cells (Tregs) leads to development of autoimmunity in experimental mouse models. However, the miRNA expression signature characterizing Tregs of autoimmune diseases, such as rheumatoid arthritis (RA) has not been determined yet. Moreover, the technical limitations prevented the analysis of such minute T-cell population as naive and memory Tregs. In this study we have used a microarray approach to comprehensively analyze miRNA expression signatures of naive Tregs (CD4+CD45RO-CD25++), memory Tregs (CD4+CD45RO+CD25+++), as well as conventional naive (CD4+CD45RO-CD25-) and memory (CD4+CD45RO+CD25-) T-cells (Tconvs) derived from peripheral blood of RA patients, and matched healthy controls. Differential expression of selected miRNAs was validated by TaqMan-based qRT-PCR. We found a positive correlation between increased expression of miR-451 in T-cells of RA patients and disease activity score (DAS28), ESR levels, and serum levels of IL-6. Moreover, we found characteristic, disease and treatment independent, global miRNA expression signatures defining naive Tregs, memory Tregs, naive Tconvs and memory Tconvs. The analysis allowed us to define miRNAs characteristic for a general naive phenotype (e.g. miR-92a), a general memory phenotype (e.g. miR-21, miR-155), and most importantly miRNAs specifically expressed in both naive and memory Tregs, defining as such the Treg phenotype (i.e. miR-146a, miR-3162, miR-1202, miR-1246a, and miR-4281). MicroRNA profiling was performed in four CD4+ T-cell subsets: naive Tconventional (CD3+CD8-CD45RO-CD25-), naive Tregulatory (CD3+CD8-CD45RO-CD25+), memory Tconventional (CD3+CD8-CD45RO+CD25-), and memory Tregulatory (CD3+CD8-CD45RO+CD25+) derived from 2 healthy controls, and 6 rheumatoid arthritis patients (total n=8).
2014-01-22 | E-GEOD-50646 | biostudies-arrayexpress
Project description:Gene expression data of primary human naive and memory CD4+T lymphocytes purified from peripheral blood are generated to be analyzed in different ways such as for traditional searching of differentially expressed genes between the two cell subsets or in combination to in-silico data of microRNAs target prediction for microRNAs known to be characteristically expressed in the two cell subsets. Two cell subsets (cell types) FACS purified from peripheral blood of six samples/healthy donors (samples #3,5,6,7,026,065). Naive CD4+ T cells were extracted from all 6 samples and 6 biological replicas were obtained (3N, 5N, 6N, 7N, 026N, 065N), while memory CD4+T cells were extracted from 4 samples and 4 biological replicas were obtained (3m, 5m, 6m, 7m). Both naive and memory replicas from samples 3, 5, 6 and 7 were hybridized onto two beadsarrays each while those from samples 026 and 065 were hybridized on 1 beadsarray each (for a total of 18 beadsarrays used). For analysis purposes naive cells samples 3N, 5N, 6N and 7N can be considered paired with memory samples 3m, 5m, 6m and 7m respectively, since they are obtained from the same blood samples/healthy donors.
2011-06-26 | E-GEOD-22880 | biostudies-arrayexpress
Project description:Buffy coats from four independent human donors were enriched for CD4+ cells using MACS CD4 beads and LS columns. Cells were subsequently sorted into Naïve, Central Memory and Effector Memory using following markers: Naive: CD4+CD25–CD45RA+CCR7+; Central Memory: CD4+CD25–CD45RA–CCR7+; Effector Memory: CD4+CD25-CD45RA-CCR7-. Total RNA from these cell subsets was extracted and 100ng was used for Nanostring SPRINT run according to manufacturer's instructions. Overall aim of the experiment is assessing the expression level of human T helper cell miRNome.
2022-01-10 | GSE161098 | GEO
Project description:The present project reports the quantitative proteome of different B-cell populations corresponding to the last steps of B-cell differentiation (i.e., naive (N), centroblast (CB), centrocytes (CC), memory cells (M), plasmablasts (PC).
2021-05-03 | PXD006191 | Pride