Dynamics of Transcription Regulation in Human Bone Marrow Myeloid Differentiation to Mature Blood Neutrophils
| Autor: | Eva M. Janssen-Megens, Myrto Kostadima, Marta Gut, Farzin Pourfarzad, Sebastian Ullrich, Mattia Frontini, Luigi Grassi, Daniel Rico, Ida H. Hiemstra, Alfonso Valencia, Ehsan Habibi, Juliane Perner, Anton T.J. Tool, Hinri Kerstens, Angelika Merkel, Ivo Gut, Paul Flicek, Erik Mul, Taco W. Kuijpers, Ernesto Lowy, Enrique Carrillo-de-Santa-Pau, Joost H.A. Martens, Kim Berentsen, Laura Clarke, Marie-Laure Yaspo, Timo K. van den Berg, Willem H. Ouwehand, Avik Datta, Guoqiang Yi, Hendrik G. Stunnenberg, Dirk Roos, Martin Vingron, Matthias Linser, Simon Heath, Felipe Were |
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| Přispěvatelé: | Dutch Cancer Foundation, European Research Council, British Health Foundation, Wellcome Trust, European Molecular Biology Organization, Bristol-Myers Squibb, Medical Research Council (Reino Unido), Paediatric Infectious Diseases / Rheumatology / Immunology, Landsteiner Laboratory, ARD - Amsterdam Reproduction and Development, Molecular cell biology and Immunology, Pediatric surgery, APH - Aging & Later Life, Grassi, Luigi [0000-0002-6308-7540], Frontini, Mattia [0000-0001-8074-6299], Ouwehand, Willem [0000-0002-7744-1790], Apollo - University of Cambridge Repository |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Myeloid Neutrophils epigenome Bone Marrow Cells Biology Myeloid differentiation General Biochemistry Genetics and Molecular Biology Article Transcriptome 03 medical and health sciences Epigenome 0302 clinical medicine medicine Transcriptional regulation Cytotoxic T cell Humans Epigenetics lcsh:QH301-705.5 Molecular Biology Neutrophil neutrophil Cell Differentiation Chromatin 3. Good health Respiratory burst Cell biology 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) Gene Expression Regulation 030220 oncology & carcinogenesis myeloid differentiation Bone marrow transcriptome |
| Zdroj: | Cell reports Cell reports, 24(10), 2784-2794. Cell Press Cell Reports, 24(10), 2784-2794. Cell Press Cell Reports, 24, 10, pp. 2784-2794 Repisalud Instituto de Salud Carlos III (ISCIII) Cell Reports, 24, 2784-2794 Cell Reports Grassi, L, Pourfarzad, F, Ullrich, S, Merkel, A, Were, F, Carrillo-de-Santa-Pau, E, Yi, G, Hiemstra, I H, Tool, A T J, Mul, E, Perner, J, Janssen-Megens, E, Berentsen, K, Kerstens, H, Habibi, E, Gut, M, Yaspo, M L, Linser, M, Lowy, E, Datta, A, Clarke, L, Flicek, P, Vingron, M, Roos, D, van den Berg, T K, Heath, S, Rico, D, Frontini, M, Kostadima, M, Gut, I, Valencia, A, Ouwehand, W H, Stunnenberg, H G, Martens, J H A & Kuijpers, T W 2018, ' Dynamics of Transcription Regulation in Human Bone Marrow Myeloid Differentiation to Mature Blood Neutrophils ', Cell Reports, vol. 24, no. 10, pp. 2784-2794 . https://doi.org/10.1016/j.celrep.2018.08.018 Cell Reports, Vol 24, Iss 10, Pp 2784-2794 (2018) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2018.08.018 |
| Popis: | 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. The work presented here was supported by the Landsteiner Foundation forBlood Transfusion Research (LSBR-1121 to T.W.K.) and by the Dutch CancerFoundation (KUN 2011-4 937 to J.H.A.M.). The work was funded by a grantfrom the European Commission 7th Framework Program (FP72007-2013,grant 282510, BLUEPRINT). M.F. ssupported sh Heart Foundation(BHF) Cambridge Centre of Excellence (RE/13/6/30180). Additional support wasrovided by the Wellcome Trust (WT108749/Z/15/Z to P.F.) and by the Eu-ropean Molecular Biology Laboratory (E.L., A.D.,L.C., P.F.). Research in theOuwehand laboratory is also supported by grants from Bristol-Myers Squibb,the British Heart Foundation, the Medical Research Council, the National Insti-tutefor Health Research (NIHR) (W.H.O. is senior investigator), and NHSBlood and Transplant (NHSB T). Sí |
| Databáze: | OpenAIRE |
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