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Single-cell transcriptomics of adult gd T-cell lineage commitment highlights its TCR-instructive nature

ABSTRACT: Single-cell transcriptomics of adult gd T-cell lineage commitment highlights its TCR-instructive nature

PROVIDER: PRJNA765015 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15998113_1.fastq.gz	Fastqsanger.gz
	SRR15998113_2.fastq.gz	Fastqsanger.gz
	SRR15980114_1.fastq.gz	Fastqsanger.gz
	SRR15980114_2.fastq.gz	Fastqsanger.gz
	SRR15998114_1.fastq.gz	Fastqsanger.gz

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Single-cell transcriptomics of adult gd T-cell lineage commitment highlights its TCR-instructive nature II

Project description:Single-cell transcriptomics of adult gd T-cell lineage commitment highlights its TCR-instructive nature II

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Single-cell transcriptomics of adult gd T-cell lineage commitment highlights its TCR-instructive nature I

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Project description:Single cell RNA-seq study of T lymphocyte differentiation WT and LAT deficient mice in order to deciphy gd T-cell lineage commitment.

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Single-cell transcriptomics of adult gd T-cell lineage commitment highlights its TCR-instructive nature

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c-Maf is an essential commitment factor for IL-17-producing gd T cells [ATAC-seq]

Project description:IL-17-producing gd T (Tgd17) cells are early mediators of immunity and autoimmunity that undergo effector programming in the thymus. While Vg subset-restricted regulators of Tgd17 specialization are known, a universal type 17 commitment factor for all gd T cells remains undefined. In this study, we identify the transcription factor c-Maf as an essential and uniform regulator of Tgd17 differentiation and maintenance. The absolute lineage block caused by Maf deficiency reveals a critical effector acquisition checkpoint at the immature CD24+ CD45RBlo gd thymocyte stage. Here, c-Maf enforces Tgd17 identity by promoting chromatin accessibility and activating expression of lineage-defining RORgt and key type 17 program genes, while coordinately antagonizing the negative regulator TCF1, which promotes the alternative IFNg+ Tgd1 fate. During specialization, c-Maf expression is tuned by gdTCR signal strength, implicating c-Maf as a rheostat controlling effector gd T cell generation and connecting gdTCR signals to a core node in the Tgd17 network.

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c-Maf is an essential commitment factor for IL-17-producing gd T cells [RNA-seq]

2018-12-03 | GSE120425 | GEO

Integration of epigenetic and transcriptional mechanisms governs functional commitment versus plasticity of gd T cell subsets

2013-09-01 | GSE42098 | GEO

Integration of epigenetic and transcriptional mechanisms governs functional commitment versus plasticity of gd T cell subsets

Project description:gd T cells are major innate sources of interleukin-17 (IL-17) and interferon-g (IFN-g), which are differentially produced by two thymically-derived subsets segregated on CD27 expression. However, the molecular mechanisms that program the functional differentiation of gd cells remain incompletely understood. Here we show that CD27+ gd cells are epigenetically committed to express Ifng but not Il17, whereas CD27- gd cells spontaneously make IL-17 but can be induced to produce IFN-g under specific inflammatory conditions. This M-bM-^@M-^\plasticM-bM-^@M-^] behavior of CD27- gd cells associates with permissive histone H3 marks at loci encoding Ifng and upstream M-bM-^@M-^\type 1M-bM-^@M-^] transcription factors. By contrast, Il17 and related M-bM-^@M-^\type 17M-bM-^@M-^] factors are epigenetically and transcriptionally active in CD27- but silenced in CD27+ gd cells. Hence, stable versus plastic behaviors of gd cell subsets are controlled by integrated epigenetic and transcriptional mechanisms that regulate the expression of M-bM-^@M-^\masterM-bM-^@M-^] transcription factors and effector cytokine genes. ChIP was carried out on FACS-sorted cells from pooled spleen/ lymph nodes. The following antibodies were used: anti-histone H3K4me2 (07-030, Millipore) and anti-histone H3k27me3 (07-449, Millipore). Between 105 - 106 cells were crosslinked with formaldehyde and nuclei were isolated and sonicated with a Sanyo Soniprep 150 at an amplitude of 10 microns with 17 times 10s bursts, resulting in 200M-bM-^@M-^S400bp chromatin fragments. IP was carried out as previously described 49. The Immunoprecipitated DNA released from crosslinked proteins was extracted with the QiaQuick kit (Qiagen) in accordance with the manufacturerM-BM-4s instructions. Deep sequencing was performed at the GeneCore facility of EMBL (http://www.genecore.embl.de/). At least 1 ng of immunoprecipitated DNA was used for library preparation according to the Illumina protocol.

2013-09-01 | E-GEOD-42098 | biostudies-arrayexpress

c-Maf is an essential commitment factor for IL-17-producing gd T cells

Project description:c-Maf is an essential commitment factor for IL-17-producing gd T cells

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