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Stat6 mediated regulation of transcription to initiate Th2 program in human T cells

ABSTRACT: This SuperSeries is composed of the following subset Series: GSE17850: Genome-wide detection of STAT6 binding sites in IL-4 treated naive human CD4+ T cells GSE17851: Genome-wide analysis of STAT6 target genes in IL-4 treated human cord blood CD4+ cells GSE17974: Genome-wide analysis of early transcriptional events induced by cytokine IL-4 in human cord blood CD4+ T cells Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Henna Järvenpää

PROVIDER: E-GEOD-18017 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Genome-wide analysis of STAT6 target genes in IL-4 treated human cord blood CD4+ cells

Project description:STAT6 is a major transcription factor driving the polarization of Th2 cells in response to cytokine IL-4. Here we have analyzed on a genome wide level the STAT6 mediated gene expression after IL-4 induction in naive human CD4+ T cells. RNAi mediated STAT6 knockdown was used to reveal the genes specifically regulated by STAT6. Total RNA from STAT6 siRNA treated cord blood CD4+ T cells 12, 24, 48 or 72 hours after culturing the cells in activating (antiCD3+antiCD28) plus or minus IL-4 conditions was compared to total RNA from nonspecific control siRNA treated cells. All together 18 samples were analyzed and 3 biological replicates of the culture were performed for a total of 54 samples.

2010-07-29 | E-GEOD-17851 | biostudies-arrayexpress

Genome-wide analysis of early transcriptional events induced by cytokine IL-4 in human cord blood CD4+ T cells

Project description:The aim of this dataset was to study in detail the transcription kinetics initiated by cytokine IL-4 in early differentiation of Th2 cells. Total RNA obtained from activated and IL-4 & anti-IL-12 treated cord blood CD4+ T cells, 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after initiation of the cultures, compared to cells which were only activated. 57 samples were analyzed from three biological replicates of the culture. Two of the samples were discarded from the further data analysis due to compromised quality (samples 8=Th0.4h.1 and 11=Th2.6h.1).

2010-06-25 | E-GEOD-17974 | biostudies-arrayexpress

An integrative computational systems biology approach identifies differentially regulated dynamic transcriptome signatures which drive the initiation of human T helper cell differentiation

Project description:The aim of this dataset was to study in detail the transcription kinetics initiated by cytokines IL-12 and IL-4 in early differentiation of Th1 and Th2 cells, respectively. Total RNA obtained from activated and IL-12 or IL-4 & anti-IL-12 treated cord blood CD4+ T cells, 12, 24, 48, and 72 hours after initiation of the cultures, compared to cells which were only activated. 37 samples were analyzed from three biological replicates of the culture. Several (26) of the Samples in this Series represent a re-analysis of CEL files originally submitted as GEO Series GSE17974. Please see associations on each Sample record.

2012-11-09 | E-GEOD-32959 | biostudies-arrayexpress

Genome-wide detection of STAT6 binding sites in IL-4 treated naive human CD4+ T cells

Project description:STAT6 is a major transcription factor driving the polarization of Th2 cells in response to IL-4. STAT6 is phosphorylated by Jak1 and Jak3 kinases at the IL-4 receptor, after which phosphorylated STAT6 forms a homodimer and translocates into the nucleus. There STAT6 binds to specific DNA sequences, regulating the transcription of its target genes. Here we have analyzed on a genome wide level the STAT6 binding sites, after 1h and 4h of IL-4 induction, in naive human CD4+ T cells. Keywords: SRA Altogether 5 samples from 1 biological replicate were analyzed. Activated and IL-4 treated samples were compared to only activated or untreated samples to identify unique STAT6 binding sites after IL-4 induction.

2010-06-25 | E-GEOD-17850 | biostudies-arrayexpress

ATF3 is a positive regulator of human IFN gene expression

Project description:The aim of this study was to identify genes regulated by IL-12, IL-18 and IFN-alpha during early differentiation of human Th1 cells Human cord blood CD4+ T cells were activated via TCR and cultured in the presence of IL-12, IFN-alpha or IL-12+IL-18. Cytokine induced gene expression was compared to activation only after 2h, 6h or 48h of cell culture. 12 samples were analyzed in total.

2010-04-11 | E-GEOD-20198 | biostudies-arrayexpress

T helper type 2 and type 0 RNA-seq time course

Project description:CD4+ T cells were extracted from mouse and human. They were activated in vitro with CD3/28 and cultured with Il4

2017-11-02 | E-MTAB-6300 | biostudies-arrayexpress

Transcription profiling of human Th cells induced to polarize to Th1 or Th2 direction in the presence or absence of TGFbeta

Project description:Th1 and Th2 cells arise from a common precursor cell in response to triggering through the TCR and cytokine receptors for IL-12 or IL-4. This leads to activation of complex signaling pathways, which are not known in detail. Disturbances in the balance between type 1 and type 2 responses can lead to certain immune-mediated diseases. Thus, it is important to understand how Th1 and Th2 cells are generated. To clarify the mechanisms as to how IL-12 and IL-4 induce Th1 and Th2 differentiation and how TGF-beta can inhibit this process, we have used oligonucleotide arrays to examine the early polarization of Th1 and Th2 cells in the presence and absence of TGF-beta after 0, 2, 6 and 48 hours of polarization. Experiment Overall Design: This study includes altoghether 34 samples. Six different types of treatments (Thp, Th0, Th1, Th2, Th1+TGFbeta, Th2+TGFbeta) were studied at 4 time points (0, 2, 6 and 48h). There are two biological replicates, for both time series, consisting of pooled samples derived from different individuals. The early time points (0, 2 and 6h) and late time point (0 and 48h) were done in separate experiments (cell from different individuals), because of the limited number of the cells obtained from each the cord blood.

2007-12-12 | E-GEOD-2770 | biostudies-arrayexpress

Genome wide STAT3 RNAi expression profiling data from Thp,Th0 and Th17 cells

Project description:STAT3 is an immidiate regulator of Th17 differentiation. STAT3 difieciency downmodulate Th17 specific genes and Th17 responses. Therefore, we intend to identify genome wide targets of STAT3. We used microarrays to profile gene expression of STAT3 regulated genes during Th17 polarization. Total RNA was extracted from non-targeting and STAT3 siRNA treated Thp, Th0 and Th17 cell samples from different time points. Total RNA subjected to poly-A selection and hybridization on Affymetrix microarrays.

2017-05-03 | E-GEOD-67185 | biostudies-arrayexpress

Gene array for identifying molecules involved in IL-10 regulation during Th17 polarization

Project description:IL-10 production by Th17 cells is critical for limiting autoimmunity and inflammatory responses. Gene array analysis on Stat6 and T-bet double deficient Th17 cells identified the Th2 transcription factor c-Maf to be synergistically up-regulated by IL-6 plus TGFbeta, and associated with Th17 IL-10 production. Both c-Maf and IL-10 induction during Th17 polarization depended on Stat3, but not Stat6 or Stat1, and mechanistically differed from IL-10 regulation by Th2 or IL-27 signals. TGFbeta was also synergistic with IL-27 to induce c-Maf, and induced Stat1 independent IL-10 expression in contrast to IL-27 alone. Retroviral transduction of c-Maf was able to induce IL-10 expression in Stat6 deficient CD4 and CD8 T cells, and c-Maf directly transactivated IL-10 gene expression through binding to a MARE motif in the IL-10 promoter. Together, these data reveal a novel role for c-Maf in regulating T effector development, and suggest that TGFbeta may antagonize Th17 immunity by IL-10 production through c-Maf induction. Our recent studies showed that IL-6 combined with TGFbeta differed from IL-6 combined with IL-23 for IL-10 production and pathogenic activities in CD4 T cells deficient in Stat6 and T-bet, despite similar IL-17 production. We performed gene array analysis on Stat6 and T-bet double deficient cells. We rationalized that by comparing gene expression in cells treated with IL-6 plus TGFbeta versus TGFbeta alone, we would be able to identify genes specific for standard Th17 polarization, and responsible for both IL-17 and IL-10 expression. By next comparing gene expression in cells treated with IL-6 plus TGFbeta versus IL-6 plus IL-23, we could eliminate molecules involved solely in IL-17 regulation, and obtain genes specifically responsible for IL-10 regulation.

2009-03-03 | E-GEOD-15029 | biostudies-arrayexpress

Expression and regulation of lincRNAs during T cell development and differentiation

Project description:Although lincRNAs are implicated in regulating gene expression in various tissues, little is known about lincRNA transcriptomes in the T cell lineages. Here we identify 1,524 lincRNAs in 42 T cell samples from early T cell progenitors to terminally differentiated T helper subsets. Our analysis revealed highly dynamic and cell-specific expression patterns of lincRNAs during T cell differentiation. Importantly, these lincRNAs are located in genomic regions enriched for protein-coding genes with immune-regulatory functions. Many of these transcripts are bound and regulated by the key T cell transcription factors, T-bet, GATA3, STAT4 and STAT6. We demonstrate that the lincRNA LincR-Ccr2-5'AS, together with GATA3, is an essential component of a regulatory circuit in Th2-specific gene expression. To obtain comprehensive profiles of lincRNA expression during the development and differentiation of T cell lineages, we purified CD4-CD8 double negative (DN) cells (DN1, DN2, DN3 and DN4), double positive (DP) cells (CD4+CD8+CD3low and CD4+CD8intCD69+), single positive (SP) CD4 and CD8 cells, and thymic-derived regulatory T cells (tTreg) from thymi of C57BL/6 mice. Additionally, we obtained Th1, Th2, Th17 and iTreg cells by in vitro differentiation of naM-CM-/ve CD4 T cells for a various length of time in culture (4 hrs, 8 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 1 week, 2weeks). Total and/or polyadenylated RNAs from these cells was analyzed using RNA-Seq. To understand the regulation of lincRNAs by T cell master regulator T-bet, we compared the transcriptiomes between T-bet deficient Th1 cells and control Th1 cells. We did similar experiments and data analysis for STAT4 (Th1), GATA3 (Th2) and STAT6 (Th2). Finally, to address the funcation of a Th2-specifically expressed lincRNA, lincR-Ccr2-5'AS, we compared the transcriptomes between lincR-Ccr2-5'AS knockdown Th2 cells and control Th2 cells.

2013-09-23 | E-GEOD-48138 | biostudies-arrayexpress

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