Mus musculus
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ABSTRACT:
PROVIDER: PRJNA385079 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Epigenetic activation during Th17 cell differentiation is impaired after TRIM28 deletion
| PRJNA427793 | ENA
Project description:Cell fate decision is mediated by epigenetic mechanisms. We have analyzed naive T cell differentiation into Th17 cells, which is regulated by environmental cytokines and their downstream transcription factors. RORγt is a lineage-specific master transcription factor for Th17 cells. Although epigenetic mechanisms have been implicated in Th17 cell differentiation, how transcription factors interact to activate epigenetic program is unclear. Here we show that tripartite motif containing 28 (TRIM28) expression in Th17 cells is required for cytokine production and autoimmune diseases. Genome-wide occupancy analysis reveals that TRIM28 bound regions contain many super-enhancers, which are impaired after TRIM28 or STAT3 but not RORγt deletion. Importantly, TRIM28 exists in a complex with STAT3 and RORγt; TRIM28 recruitment to the Il17 gene requires STAT3, and further promotes RORγt recruitment. TRIM28 thus is a key player in the epigenetic activation during T cell differentiation.
2018-02-28 | GSE108598 | GEO
Project description:Cell fate decision is mediated by epigenetic mechanisms. We have analyzed naive T cell differentiation into Th17 cells, which is regulated by environmental cytokines and their downstream transcription factors. RORγt is a lineage-specific master transcription factor for Th17 cells. Although epigenetic mechanisms have been implicated in Th17 cell differentiation, how transcription factors interact to activate epigenetic program is unclear. Here we show that tripartite motif containing 28 (TRIM28) expression in Th17 cells is required for cytokine production and autoimmune diseases. Genome-wide occupancy analysis reveals that TRIM28 bound regions contain many super-enhancers, which are impaired after TRIM28 or STAT3 but not RORγt deletion. Importantly, TRIM28 exists in a complex with STAT3 and RORγt; TRIM28 recruitment to the Il17 gene requires STAT3, and further promotes RORγt recruitment. TRIM28 thus is a key player in the epigenetic activation during T cell differentiation.
2018-02-22 | GSE98427 | GEO
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description:PGCs undergo two distinct stages of demethylation before reaching a hypomethylated ground state at E13.5. Stage 1 occurs between E7.25- E9.5 in which PGCs experience a global loss of cytosine methylation. However, discreet loci escape this global loss of methylation and between E10.5-E13.5, stage 2 of demethylation takes place. In this stage these loci are targeted by Tet1 and Tet2 leading to the loss of the remaining methylation and resulting in the epigenetic ground state. Our data shows that Dnmt1 is responsible for maintaining the methylation of loci that escape stage 1 demethylation, and that it functions in a UHRF1 independent manner. Our data further demonstrates that when these loci lose methylation prior to stage 2 it results in early activation of the meiotic program, which leads to precocious differentiation of the germ line resulting in a decreased pool of PGCs in the embryo and subsequent infertility in adult mice.
2016-09-13 | GSE74938 | GEO
Project description:Carbo2013 - Cytokine driven CD4+ T Cell differentiation and phenotype plasticity
CD4+ T cells can differentiate into different phenotypes
depending on the cytokine milieu. Here a computational and mathematical model with sixty ordinary differential equations representing a CD4+ T cell differentiating into either Th1, Th2, Th17 or iTreg cells, has been constructed.
The model includes cytokines,
nuclear receptors and transcription factors that define fate
and function of CD4+ T cells. Computational simulations
illustrate how a proinflammatory Th17 cell can undergo
reprogramming into an anti-inflammatory iTreg phenotype
following PPARc activation.
This model is described in the article:
Systems Modeling of Molecular Mechanisms Controlling Cytokine-driven CD4+ T Cell Differentiation and Phenotype Plasticity.
Carbo A, Hontecillas R, Kronsteiner B, Viladomiu M, Pedragosa M, Lu P, Philipson CW, Hoops S, Marathe M, Eubank S, Bisset K, Wendelsdorf K, Jarrah A, Mei Y, Bassaganya-Riera J
PLoS Computational Biology [2013, 9(4):e1003027]
Abstract:
Differentiation of CD4+ T cells into effector or regulatory phenotypes is tightly controlled by the cytokine milieu, complex intracellular signaling networks and numerous transcriptional regulators. We combined experimental approaches and computational modeling to investigate the mechanisms controlling differentiation and plasticity of CD4+ T cells in the gut of mice. Our computational model encompasses the major intracellular pathways involved in CD4+ T cell differentiation into T helper 1 (Th1), Th2, Th17 and induced regulatory T cells (iTreg). Our modeling efforts predicted a critical role for peroxisome proliferator-activated receptor gamma (PPARγ) in modulating plasticity between Th17 and iTreg cells. PPARγ regulates differentiation, activation and cytokine production, thereby controlling the induction of effector and regulatory responses, and is a promising therapeutic target for dysregulated immune responses and inflammation. Our modeling efforts predict that following PPARγ activation, Th17 cells undergo phenotype switch and become iTreg cells. This prediction was validated by results of adoptive transfer studies showing an increase of colonic iTreg and a decrease of Th17 cells in the gut mucosa of mice with colitis following pharmacological activation of PPARγ. Deletion of PPARγ in CD4+ T cells impaired mucosal iTreg and enhanced colitogenic Th17 responses in mice with CD4+ T cell-induced colitis. Thus, for the first time we provide novel molecular evidence in vivo demonstrating that PPARγ in addition to regulating CD4+ T cell differentiation also plays a major role controlling Th17 and iTreg plasticity in the gut mucosa.
Author's comment:
CD4+ T cell computational model (Version 1.4)
Steady state corrected. There was a problem in the internalization of IL-17 in its mathematical function.
This model is hosted on BioModels Database
and identified
by: MODEL1304230001
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2013-05-09 | BIOMD0000000451 | BioModels
Project description:Activated T cells differentiate into functional subsets which require distinct metabolic programs. Glutaminase (GLS) converts glutamine to glutamate to provide substrate for the tricarboxylic acid cycle and epigenetic reactions and here we identify a key role for GLS in T cell activation and specification. Though GLS-deficiency diminished T cell activation, proliferation and impaired differentiation of Th17 cells, loss of GLS also increased Tbet and Interferon-γ expression and CD4 Th1 and CD8 CTL effector cell differentiation. These changes were mediated by differentially altered gene expression and chromatin accessibility, leading to increased sensitivity of Th1 cells to IL-2 mediated mTORC1 signaling. In vivo, GLS-null T cells failed to drive a Th17 mediated Graft-vs-Host Disease model. Transient inhibition of GLS, however, increased Th1 and CTL T cell numbers in viral and chimeric antigen receptor models. Glutamine metabolism thus has distinct roles to promote Th17 but constrain Th1 and CTL effector cell differentiation.
2018-09-01 | E-MTAB-6648 | biostudies-arrayexpress
Project description:TRIM28 interacts with PGR and ESR1 in both human and mouse uterus to modulate estrogen and progesterone signaling. Knocking down of TRIM28 in the human endometrial stromal cells impaired decidualization in vitro. Deletion of TRIM28 from mouse uterus disrupted uterine stromal decidualization leading to infertility. Additionally, TRIM28 deletion caused abnormal accumulation of TRIM28 positive and PGR negative cells in the stroma.
2023-06-04 | GSE226623 | GEO
Project description: Not available
| S-EPMC395764 | biostudies-literature
Project description: Not available
| S-EPMC4490682 | biostudies-literature