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Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells. [Epigenetics]

ABSTRACT: Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells. [Epigenetics]

PROVIDER: PRJNA433824 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6706600_1.fastq.gz	Fastqsanger.gz
	SRR6706600_2.fastq.gz	Fastqsanger.gz
	SRR6706610.fastq.gz	Fastqsanger.gz
	SRR6706620.fastq.gz	Fastqsanger.gz
	SRR6706601_1.fastq.gz	Fastqsanger.gz

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Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells.

Project description:Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells.

| PRJNA433827 | ENA

Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells. [Epigenetics]

Project description:Human fetal naïve T cells preferentially differentiate into CD25hiFOXP3hi regulatory T (Treg) cells upon T cell receptor (TCR) stimulation, which contribute to the generation of immunotolerance in the developing human fetus. We utilized ATACseq and H3K27ac ChIPseq to characterize the human fetal naive T cell epigenome relative to that of adult naive T cells and Treg cells. Fetal naive T cells share a partial Treg epigenome with increased chromatin accessibility and H3K27ac enrichment at a subset of Treg-specific enhancers.

2019-11-22 | GSE110468 | GEO

Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells. [RNA-Seq - ex vivo]

Project description:Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells. [RNA-Seq - ex vivo]

| PRJNA433825 | ENA

Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells [RNA-Seq - induced Treg cells].

Project description:Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells [RNA-Seq - induced Treg cells].

| PRJNA544098 | ENA

Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells [RNA-Seq - induced Treg cells].

Project description:RNA sequencing was used to compare the transcriptome of in vitro differentiated adult and fetal induced Treg (iTreg) cells that were culture with IL-2 alone or supplemented with additional TGFb. Additionally, fetal iTreg cells also had Helios knocked out by CRISPR-Cas9 editing, with paired samples treated with the Helios guide RNA1 (HeliosKO) or with the non-targeting control (HeliosWT). Differential gene expression was assessed using generalised linear model designs. This revealed that fetal iTreg cells retain a expression of Treg-specific signature previously identified to be unregulated in primary ex vivo fetal naive T cells, and this signature was not expressed by adult iTreg cells. Helios expression then regulates the Treg-specific transcriptome within fetal iTreg cells by enhancing upregulation of genes associated with Treg differentiation and function, and repressing genes associated with effector specification and pro-inflammatory function.

2019-11-22 | GSE131589 | GEO

Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells. [RNA-Seq - ex vivo]

Project description:RNA sequencing was used to compare the transcriptome of ex vivo isolated adult and fetal naïve and regulatory T (Treg) cells. A Treg-specific transcriptome was defined by genes upregulated and downregulated preferentially in adult and fetal Treg cells relative to adult naive T cells. Fetal naive T cells show an intermediate expression of genes in the Treg-specific transcriptome.

2019-11-22 | GSE110469 | GEO

Helios enhances the preferential differentiation of human fetal CD4+ naive T cells into regulatory T cells.

Project description:T cell receptor (TCR) stimulation and cytokine cues drive the differentiation of CD4+ naïve T cells into effector T cell populations with distinct proinflammatory or regulatory functions. Unlike adult naïve T cells, human fetal naïve CD4+ T cells preferentially differentiate into FOXP3+ regulatory T (Treg) cells upon TCR activation independent of exogenous cytokine signaling. This cell-intrinsic predisposition for Treg differentiation is implicated in the generation of tolerance in utero; however, the underlying mechanisms remain largely unknown. Here, we identify epigenetic and transcriptional programs shared between fetal naïve T and committed Treg cells that are inactive in adult naïve T cells and show that fetal-derived induced Treg (iTreg) cells retain this transcriptional program. We show that a subset of Treg-specific enhancers is accessible in fetal naïve T cells, including two active superenhancers at Helios Helios is expressed in fetal naïve T cells but not in adult naïve T cells, and fetal iTreg cells maintain Helios expression. CRISPR-Cas9 ablation of Helios in fetal naïve T cells impaired their differentiation into iTreg cells upon TCR stimulation, reduced expression of immunosuppressive genes in fetal iTreg cells such as IL10, and increased expression of proinflammatory genes including IFNG Consequently, Helios knockout fetal iTreg cells had reduced IL-10 and increased IFN-γ cytokine production. Together, our results reveal important roles for Helios in enhancing preferential fetal Treg differentiation and fine-tuning eventual Treg function. The Treg-biased programs identified within fetal naïve T cells could potentially be used to engineer enhanced iTreg populations for adoptive cellular therapies.

| S-EPMC7340007 | biostudies-literature

Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells.

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-11-22 | GSE110472 | GEO

Influence of ATL-type Helios overexpression or WT-Helios/Ikaros knockdown on gene expression profile in Jurkat cells

Project description:It has been known that aberrant isoforms of Ikaros family ptoteins are expressed in malignant cells. We identified that PBMC of ATL (acute T-cell leukemia) patients expresses different patterns of Helios isoforms compared with normal PBMC. In order to investigate the biological impact of ATL-type Helios isoform, we conducted complehensive gene expression analyses in Jurkat cells overexpressing ATL-type Helios. Also, we investigated the influence of WT-Helios or WT-Ikaros knockdown on the gene expression profile and compared with that of the cells with ATL-type Helios overexpression. Total RNA samples from Jurkat cells were subjected to Cy-3 labeling followed by human whole genome gene expression microarray analyses.

2013-03-31 | E-GEOD-41796 | biostudies-arrayexpress

Influence of ATL-type Helios overexpression or WT-Helios/Ikaros knockdown on gene expression profile in Jurkat cells

2013-03-31 | GSE41796 | GEO