Dynamics of transcription regulation in human bone marrow myeloid differentiation to mature blood neutrophils
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- dc.contributor.author Grassi, Luigi
- dc.contributor.author Ullrich, Sebastian, 1984-
- dc.contributor.author Merkel, Angelika
- dc.contributor.author Gut, Marta
- dc.contributor.author Heath, Simon
- dc.contributor.author Gut, Ivo Glynne
- dc.contributor.author Kuijpers, Taco W.
- dc.date.accessioned 2019-11-04T08:48:01Z
- dc.date.available 2019-11-04T08:48:01Z
- dc.date.issued 2018
- dc.description.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.
- dc.description.sponsorship The work was funded by a grant from the European Commission 7th Framework Program (FP7/2007-2013, grant 282510, BLUEPRINT). M.F. is supported by the British Heart Foundation (BHF) Cambridge Centre of Excellence (RE/13/6/30180). Additional support was provided by the Wellcome Trust (WT108749/Z/15/Z to P.F.) and by the European Molecular Biology Laboratory (E.L., A.D., L.C., P.F.). Research in the Ouwehand laboratory is also supported by grants from Bristol-Myers Squibb, the British Heart Foundation, the Medical Research Council, the National Institute for Health Research (NIHR) (W.H.O. is NIHR senior investigator), and NHS Blood and Transplant (NHSBT).
- dc.format.mimetype application/pdf
- dc.identifier.citation Grassi L, Pourfarzad F, Ullrich S, Merkel A, Were F, Carrillo-de-Santa-Pau E et al. Dynamics of transcription regulation in human bone marrow myeloid differentiation to mature blood neutrophils. Cell Rep. 2018; 24(10):2784-2794. DOI 10.1016/j.celrep.2018.08.018
- dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2018.08.018
- dc.identifier.issn 2211-1247
- dc.identifier.uri http://hdl.handle.net/10230/42591
- dc.language.iso eng
- dc.publisher Elsevier
- dc.relation.ispartof Cell Rep. 2018; 24(10):2784-2794
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/282510
- dc.rights © 2018. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
- dc.subject.keyword Neutrophil
- dc.subject.keyword Epigenome
- dc.subject.keyword Transcriptome
- dc.subject.keyword Myeloid differentiation
- dc.title Dynamics of transcription regulation in human bone marrow myeloid differentiation to mature blood neutrophils
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion