Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Tet2-mediated epigenetic programing of T follicular helper cell differentiation (ChIP-Seq)

ABSTRACT: Tet2-mediated demethylation is a key component of epigenetic programing that promotes lineage specific gene expression and contributes to cellular differentiation and function. While the differentiation of CD4+ T cell subsets has been studied extensively, the epigenetic programs that regulate these processes remain unclear. We report that Tet2 acts to restrict the differentiation of T follicular helper (Tfh) cells in CD4+ T cells responding to viral infection. Tet2-deficient CD4+ T cells preferentially differentiated into highly functional germinal center (GC) Tfh cells that provided enhanced help for B cell responses. Using genome-wide expression and methylation analyses combined with Foxo1 ChIPseq analysis, we found that Tet2 coordinates with multiple transcription factors, including Foxo1, to mediate the demethylation and expression of their target genes following activation.

ORGANISM(S): Mus musculus

PROVIDER: GSE183315 | GEO | 2022/06/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Tet2-mediated epigenetic programing of T follicular helper cell differentiation (RNA-Seq)

Project description:Tet2-mediated demethylation is a key component of epigenetic programing that promotes lineage specific gene expression and contributes to cellular differentiation and function. While the differentiation of CD4+ T cell subsets has been studied extensively, the epigenetic programs that regulate these processes remain unclear. We report that Tet2 acts to restrict the differentiation of T follicular helper (Tfh) cells in CD4+ T cells responding to viral infection. Tet2-deficient CD4+ T cells preferentially differentiated into highly functional germinal center (GC) Tfh cells that provided enhanced help for B cell responses. Using genome-wide expression and methylation analyses combined with Foxo1 ChIPseq analysis, we found that Tet2 coordinates with multiple transcription factors, including Foxo1, to mediate the demethylation and expression of their target genes following activation.

2022-06-15 | GSE183316 | GEO

Tet2-mediated epigenetic programing of T follicular helper cell differentiation (Methyl-Seq)

2022-06-15 | GSE182940 | GEO

Tet2 deletion in CD4+ T cells disrupts Th1 lineage commitment in memory cells and enhances T follicular helper cell recall responses

Project description:Following viral clearance, antigen-specific CD4+ T cells contract and form a pool of distinct Th1 and Tfh memory cells that possess unique epigenetic programs, allowing them to rapidly recall their specific effector functions upon rechallenge. DNA methylation programing mediated by the methylcytosine dioxygenase Tet2 contributes to balancing Th1 and Tfh cell differentiation during acute viral infection, however the role of Tet2 in CD4+ T cell memory formation and recall is unclear. Using adoptive transfer models of antigen-specific WT andTet2KO CD4+ T cells, we find that Tet2 is required for full commitment of CD4+ T cells to the Th1 lineage and that in the absence of Tet2, memory cells preferentially recall a Tfh like phenotype with enhanced expansion upon secondary challenge. These findings demonstrate an important role for Tet2 in enforcing lineage commitment and programing proliferation potential, and highlight the potential of targeting epigenetic programing to enhance adaptive immune responses.

2023-08-11 | GSE239724 | GEO

ICOS-mediated inactivation of the FOXO1 transcription factor in the differentiation of T follicular helper cells

Project description:T follicular helper (Tfh) cells constitute an essential cell type in the induction of antibodies. We report that CD4 T cells lacking Foxo1 almost uniformly became CXCR5int Tfh cells following immunization. Moreover, a Foxo1 loss-of-function complemented an Icos mutation allowing the appearance of Tfh cells along with follicular, class-switched B cells and IgG isotype anti-DNA antibodies. Similarly, FOXO1 deficient Tfh differentiation displayed a substantially reduced dependence on ICOSL. Functional and molecular analyses show that FOXO1 regulates Tfh differentiation through a broad program of gene expression exemplified by positive regulation of Icos and negative regulation of Bcl6. These results demonstrate that a key step in Tfh differentiation is the ICOS-initiated activation of the PI3K-AKT pathway resulting in the inactivation of FOXO1. Performed ChIP-seq analysis to examine the role of foxo1 in the development of Tfh cells

2013-06-01 | E-GEOD-46525 | biostudies-arrayexpress

Tet2-mediated epigenetic programing of T follicular helper cell differentiation

Project description:Tet2-mediated epigenetic programing of T follicular helper cell differentiation

| PRJNA759915 | ENA

Quantitative Analysis of Global Proteome and Lysine Acetylome for Human CD4+ T Follicular Helper Cells

Project description:Follicular helper T (Tfh) are a subset of CD4+ T helper cells that provide help to germinal center B cells and mediate the development of long-lived humoral immunity. Tfh cells dysregulation is associated with several major autoimmune diseases. Although recent studies showed Tfh cells differentiation is controlled by the transcription factor Bcl6, cytokines and cell-cell signals, limited information is available on the proteome and post-translational modifications (PTM) of proteins in human Tfh cells. In this study, using TMT labeling technique, antibody-based affinity enrichment and high-resolution LC-MS/MS analysis, we investigated quantitative proteome and acetylome in human naive CD4+ T cells and in vitro induced Tfh (iTfh) cells. In total, we identified 802 up-regulated proteins and 598 down-regulated proteins at the threshold of 1.5 folds in iTfh cells compared to naive CD4+ T cells. With the aid of intensive bioinformatics, biological process, cellular compartment, molecular function, KEGG pathway and protein-protein interaction of these differentially expressed proteins were revealed. Moreover, our acetylome data showed that 22 lysine acetylated proteins are up-regulated and 26 lysine acetylated proteins are down-regulated in iTfh cells compared to the naive CD4+ T cells, among which 11 differentially acetylated lysine residues in core histone were identified, indicating proteins acetylation and epigenetic mechanism are involved in regulating Tfh cells differentiation. These data provide a significant resource for studies of Tfh differentiation and normal and perturbed Tfh cell function.

2021-03-19 | PXD008563 | Pride

Tet2-mediated epigenetic programing of T follicular helper cell differentiation (Methyl-Seq)

Project description:Tet2-mediated epigenetic programing of T follicular helper cell differentiation (Methyl-Seq)

| PRJNA758390 | ENA

Tet2-mediated epigenetic programing of T follicular helper cell differentiation (ChIP-Seq)

Project description:Tet2-mediated epigenetic programing of T follicular helper cell differentiation (ChIP-Seq)

| PRJNA759917 | ENA

Tet2-mediated epigenetic programing of T follicular helper cell differentiation (RNA-Seq)

Project description:Tet2-mediated epigenetic programing of T follicular helper cell differentiation (RNA-Seq)

| PRJNA759918 | ENA

TET2 loss and the lymphoma-associated RHOA mutation cooperate to disrupt CD4+ T cell function through inactivation of FOXO1

Project description:Angioimmunoblastic T cell lymphoma (AITL) represents a distinctive form of peripheral T cell lymphoma with a dismissal prognosis. Recent exome sequencing in AITL patients revealed frequent coexistence of somatic mutations in the RHO GTPase (RHOAG17V) and the 5-methylcytosine oxidase TET2. Here we demonstrated that Tet2 loss and RhoAG17V cooperatively caused abnormal CD4+ T cell proliferation and differentiation by perturbing FoxO1 gene expression and its subcellular localization, an abnormality that is also detected in AITL tumor samples. Re-expression of FoxO1 attenuated aberrant immune responses induced by genetic lesions in both Tet2 and RhoA. Our findings suggest that mutational cooperativity between epigenetic factors and GTPases in adult CD4+ T cells may account for immunoinflammatory responses that are commonly associated with AITL.

2017-08-31 | GSE90976 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data