Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/6746
Título
Dynamics of Transcription Regulation in Human Bone Marrow Myeloid Differentiation to Mature Blood Neutrophils
Autor(es)
Grassi, Luigi | Pourfarzad, Farzin | Ullrich, Sebastian | Merkel, Angelika | Were, Felipe CNIC | Carrillo de SantaPau, Enrique CNIO | Yi, Guoqiang | Hiemstra, Ida H | Tool, Anton T J | Mul, Erik | Perner, Juliane | Janssen-Megens, Eva | Berentsen, Kim | Kerstens, Hinri | Habibi, Ehsan | Gut, Marta | Yaspo, Marie Laure | Linser, Matthias | Lowy, Ernesto | Datta, Avik | Clarke, Laura | Flicek, Paul | Vingron, Martin | Roos, Dirk | van den Berg, Timo K | Heath, Simon | Rico, Daniel CNIC | Frontini, Mattia | Kostadima, Myrto | Gut, Ivo | Valencia, Alfonso CNIO | Ouwehand, Willem H | Stunnenberg, Hendrik G | Martens, Joost H A | Kuijpers, Taco W
Fecha de publicación
2018-09-04
Cita
Cell Rep. 2018; 24(10):2784-2794.
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
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