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Dynamics of Transcription Regulation in Human Bone Marrow Myeloid Differentiation to Mature Blood Neutrophils.

Abstract：

:Neutrophils are short-lived blood cells that play a critical role in host defense against infections. To better comprehend neutrophil functions and their regulation, we provide a complete epigenetic overview, assessing important functional features of their differentiation stages from bone marrow-residing progenitors to mature circulating cells. Integration of chromatin modifications, methylation, and transcriptome dynamics reveals an enforced regulation of differentiation, for cellular functions such as release of proteases, respiratory burst, cell cycle regulation, and apoptosis. We observe an early establishment of the cytotoxic capability, while the signaling components that activate these antimicrobial mechanisms are transcribed at later stages, outside the bone marrow, thus preventing toxic effects in the bone marrow niche. Altogether, these data reveal how the developmental dynamics of the chromatin landscape orchestrate the daily production of a large number of neutrophils required for innate host defense and provide a comprehensive overview of differentiating human neutrophils.

journal_name

Cell Rep

journal_title

Cell reports

authors

Grassi L,Pourfarzad F,Ullrich S,Merkel A,Were F,Carrillo-de-Santa-Pau E,Yi G,Hiemstra IH,Tool ATJ,Mul E,Perner J,Janssen-Megens E,Berentsen K,Kerstens H,Habibi E,Gut M,Yaspo ML,Linser M,Lowy E,Datta A,Clarke L,F

doi

10.1016/j.celrep.2018.08.018

subject

Has Abstract

pub_date

2018-09-04 00:00:00

pages

2784-2794

issue

10

issn

2211-1247

pii

S2211-1247(18)31272-5

journal_volume

24

pub_type

杂志文章

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