The transcription factor ETS1 is an important regulator of human NK cell development and terminal differentiation | Zendy

Sylvie Taveirne | Zendy; Sigrid Wahlen | Zendy; Wouter Van Loocke | Zendy; Laura Kiekens | Zendy; Eva Persyn | Zendy; Els Van Ammel | Zendy; Katrien De Mulder | Zendy; Juliette Roels | Zendy; Laurentijn Tilleman | Zendy; Marc Aumercier | Zendy; Patrick Matthys | Zendy; Filip Van Nieuwerburgh | Zendy; Tessa Kerre | Zendy; Tom Taghon | Zendy; Pieter Van Vlierberghe | Zendy; Bart Vandekerckhove | Zendy; Georges Leclercq | Zendy

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The transcription factor ETS1 is an important regulator of human NK cell development and terminal differentiation

Author(s) -

Sylvie Taveirne,

Sigrid Wahlen,

Wouter Van Loocke,

Laura Kiekens,

Eva Persyn,

Els Van Ammel,

Katrien De Mulder,

Juliette Roels,

Laurentijn Tilleman,

Marc Aumercier,

Patrick Matthys,

Filip Van Nieuwerburgh,

Tessa Kerre,

Tom Taghon,

Pieter Van Vlierberghe,

Bart Vandekerckhove,

Georges Leclercq

Publication year - 2020

Publication title -

blood

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.515

H-Index - 465

eISSN - 1528-0020

pISSN - 0006-4971

DOI - 10.1182/blood.2020005204

Subject(s) - ets1 , biology , transcription factor , microbiology and biotechnology , chromatin immunoprecipitation , cellular differentiation , embryonic stem cell , haematopoiesis , stem cell , gene expression , promoter , gene , genetics

Natural killer (NK) cells are important in the immune defense against tumor cells and pathogens, and regulate other immune cells by cytokine secretion. Whereas murine NK cell biology has been extensively studied, knowledge about transcriptional circuitries controlling human NK cell development and maturation is limited. By generating ETS1-deficient human embryonic stem cells (hESC) and by expressing the dominant-negative ETS1 p27 isoform in cord blood (CB) hematopoietic progenitor cells (HPCs), we show that the transcription factor ETS1 is critically required for human NK cell differentiation. Genome-wide transcriptome analysis determined by RNA-sequencing combined with chromatin immunoprecipitation-sequencing (ChIP-seq) analysis reveals that human ETS1 directly induces expression of key transcription factors that control NK cell differentiation, i.e. E4BP4, TXNIP, TBET, GATA3, HOBIT and BLIMP1. In addition, ETS1 regulates expression of genes involved in apoptosis and NK cell activation. Our study provides important molecular insights into the role of ETS1 as an important regulator of human NK cell development and terminal differentiation.

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