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oai:repisalud.isciii.es:20.500.12105/67462024-11-29T23:02:13Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Grassi, Luigi author Pourfarzad, Farzin author Ullrich, Sebastian author Merkel, Angelika author Were, Felipe author Carrillo de SantaPau, Enrique author Yi, Guoqiang author Hiemstra, Ida H author Tool, Anton T J author Mul, Erik author Perner, Juliane author Janssen-Megens, Eva author Berentsen, Kim author Kerstens, Hinri author Habibi, Ehsan author Gut, Marta author Yaspo, Marie Laure author Linser, Matthias author Lowy, Ernesto author Datta, Avik author Clarke, Laura author Flicek, Paul author Vingron, Martin author Roos, Dirk author van den Berg, Timo K author Heath, Simon author Rico, Daniel author Frontini, Mattia author Kostadima, Myrto author Gut, Ivo author Valencia, Alfonso author Ouwehand, Willem H author Stunnenberg, Hendrik G author Martens, Joost H A author Kuijpers, Taco W author 2018-09-04 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. Cell Rep. 2018; 24(10):2784-2794. 10.1016/j.celrep.2018.08.018 2211-1247 22111247 Cell reports 30184510 http://hdl.handle.net/20.500.12105/6746 Epigenome Myeloid differentiation Neutrophil Transcriptome Dynamics of Transcription Regulation in Human Bone Marrow Myeloid Differentiation to Mature Blood Neutrophils