Regulation of monocyte cell fate by blood vessels mediated by Notch signalling

Jaba Gamrekelashvili, Roberto Giagnorio, Jasmin Jussofie, Oliver Soehnlein, Johan Duchene, Carlos G. Briseño, Saravana K. Ramasamy, Kashyap Krishnasamy, Anne Limbourg, Christine Häger, Tamar Kapanadze, Chieko Ishifune, Rabea Hinkel, Freddy Radtke, Lothar J. Strobl, Ursula Zimber-Strobl, L. Christian Napp, Johann Bauersachs, Hermann Haller, Koji Yasutomo, Christian Kupatt, Kenneth M. Murphy, Ralf H. Adams, Christian Weber and Florian P. Limbourg ()
Additional contact information
Jaba Gamrekelashvili: Hannover Medical School
Roberto Giagnorio: Hannover Medical School
Jasmin Jussofie: Hannover Medical School
Oliver Soehnlein: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University
Johan Duchene: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University
Carlos G. Briseño: Washington University in St Louis, School of Medicine
Saravana K. Ramasamy: Max Planck Institute for Molecular Biomedicine
Kashyap Krishnasamy: Hannover Medical School
Anne Limbourg: Hand and Reconstructive Surgery, Hannover Medical School
Christine Häger: Hannover Medical School
Tamar Kapanadze: Hannover Medical School
Chieko Ishifune: Graduate School of Medicine, Tokushima University
Rabea Hinkel: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University
Freddy Radtke: Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences, ISREC
Lothar J. Strobl: Research Unit Gene Vectors, Helmholtz Zentrum München, German Research Center for Environment and Health (GmbH)
Ursula Zimber-Strobl: Research Unit Gene Vectors, Helmholtz Zentrum München, German Research Center for Environment and Health (GmbH)
L. Christian Napp: Hannover Medical School
Johann Bauersachs: Hannover Medical School
Hermann Haller: Hannover Medical School
Koji Yasutomo: Graduate School of Medicine, Tokushima University
Christian Kupatt: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University
Kenneth M. Murphy: Washington University in St Louis, School of Medicine
Ralf H. Adams: Max Planck Institute for Molecular Biomedicine
Christian Weber: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University
Florian P. Limbourg: Hannover Medical School

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: Abstract A population of monocytes, known as Ly6Clo monocytes, patrol blood vessels by crawling along the vascular endothelium. Here we show that endothelial cells control their origin through Notch signalling. Using combinations of conditional genetic deletion strategies and cell-fate tracking experiments we show that Notch2 regulates conversion of Ly6Chi monocytes into Ly6Clo monocytes in vivo and in vitro, thereby regulating monocyte cell fate under steady-state conditions. This process is controlled by Notch ligand delta-like 1 (Dll1) expressed by a population of endothelial cells that constitute distinct vascular niches in the bone marrow and spleen in vivo, while culture on recombinant DLL1 induces monocyte conversion in vitro. Thus, blood vessels regulate monocyte conversion, a form of committed myeloid cell fate regulation.

Date: 2016
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DOI: 10.1038/ncomms12597

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