TY - JOUR
T1 - Dynamics of Transcription Regulation in Human Bone Marrow Myeloid Differentiation to Mature Blood Neutrophils
AU - Grassi, Luigi
AU - Pourfarzad, Farzin
AU - Ullrich, Sebastian
AU - Merkel, Angelika
AU - Were, Felipe
AU - Carrillo-de-Santa-Pau, Enrique
AU - Yi, Guoqiang
AU - Hiemstra, Ida H
AU - Tool, Anton T J
AU - Mul, Erik
AU - Perner, Juliane
AU - Janssen-Megens, Eva
AU - Berentsen, Kim
AU - Kerstens, Hinri
AU - Habibi, Ehsan
AU - Gut, Marta
AU - Yaspo, Marie Laure
AU - Linser, Matthias
AU - Lowy, Ernesto
AU - Datta, Avik
AU - Clarke, Laura
AU - Flicek, Paul
AU - Vingron, Martin
AU - Roos, Dirk
AU - van den Berg, Timo K
AU - Heath, Simon
AU - Rico, Daniel
AU - Frontini, Mattia
AU - Kostadima, Myrto
AU - Gut, Ivo
AU - Valencia, Alfonso
AU - Ouwehand, Willem H
AU - Stunnenberg, Hendrik G
AU - Martens, Joost H A
AU - Kuijpers, Taco W
PY - 2018/9/4
Y1 - 2018/9/4
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85052326940&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30184510
U2 - https://doi.org/10.1016/j.celrep.2018.08.018
DO - https://doi.org/10.1016/j.celrep.2018.08.018
M3 - Article
C2 - 30184510
SN - 2211-1247
VL - 24
SP - 2784
EP - 2794
JO - Cell Reports
JF - Cell Reports
IS - 10
ER -