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The transcription factor ETS1 is a master regulator of human NK cell differentiation

ABSTRACT: The transcription factor ETS1 is a master regulator of human NK cell differentiation

PROVIDER: PRJNA510769 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6176930.fastq.gz	Fastqsanger.gz
	SRR6176931.fastq.gz	Fastqsanger.gz
	SRR6176932.fastq.gz	Fastqsanger.gz
	SRR6176933.fastq.gz	Fastqsanger.gz
	SRR6176934.fastq.gz	Fastqsanger.gz

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The transcription factor ETS1 is a master regulator of human NK cell differentiation [ChIP-seq]

Project description:Natural killer (NK) cells are innate lymphoid cells that play a critical role in the direct immune defense against tumor cells and pathogens, and additionally have important immune regulatory functions by cytokine secretion. Whereas NK cell biology has been extensively studied in mouse models, transcriptional control of human NK cell differentiation is poorly understood. In this study, we generated ETS1-deficient human embryonic stem cell (hESC) clones using the CRISPR/Cas9 technology. In a complementary approach, we generated ETS1 loss-of-function cord blood hematopoietic stem cells (HSCs) by retroviral transduction of the dominant-negative ETS1 p27 isoform. We show that the transcription factor ETS1 is required for human NK cell differentiation. Transcriptome and ChIP analysis reveal that ETS1 directly regulates expression of several NK cell-linked transcription factors. Also, expression of genes involved in cytokine secretion and cytotoxic activity is ETS1-dependent, whereby these effector functions are decreased in residual NK cells developing from ETS1 loss-of-function cord blood hematopoietic stem cells. Our data show that ETS1 is a critical regulator of human NK cell development and function, and provide important insights in the underlying molecular mechanisms.

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Project description:Expression profiling of Rag2-deficient Ets1++ and Rag2-deficient Ets1-- mature NK cells and WT bone marrow progenitors, WT T cells, and WT Pro B cells WT Hematopoietic progenitors, CD4 T cells, Pro B cells, and WT and Ets1-deficient NK cells were FACs sorted. RNA was subsequently extracted, labelled, and hybridized to Affymetrix microarrays. The goal if this experiment was to identify Ets1 dependent genes in NK cells

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The transcription factor ETS1 is a master regulator of human NK cell differentiation

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VEGF promotes RNAPII pausing release through ETS1 to stimulate angiogenesis

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