title: Regulation of monocyte cell fate by blood vessels mediated by Notch signalling.
abstract: A population of monocytes, known as Ly6C(lo) 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 Ly6C(hi) monocytes into Ly6C(lo) 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.
authors: Department of Nephrology and Hypertension, Hannover Medical School, D 30625 Hannover, Germany.
authors: Jaba
authors: 0000-0001-7533-6906
authors: J
authors: Gamrekelashvili
authors: Department of Nephrology and Hypertension, Hannover Medical School, D 30625 Hannover, Germany.|Integrated Research and Treatment Center Transplantation, Hannover Medical School, D 30625 Hannover, Germany.
authors: Roberto
authors: R
authors: Giagnorio
authors: Department of Cardiology, Hannover Medical School, D 30625 Hannover, Germany.
authors: Jasmin
authors: J
authors: Jussofie
authors: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, D 80336 Munich, Germany.|Academic Medical Center, Department of Pathology, Amsterdam University, 1105 AZ Amsterdam, The Netherlands.|German Centre for Cardiovascular Research, Partner Site Munich Heart Alliance, Munich, Germany.
authors: Oliver
authors: O
authors: Soehnlein
authors: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, D 80336 Munich, Germany.
authors: Johan
authors: J
authors: Duchene
authors: Department of Pathology and Immunology, Washington University in St Louis, School of Medicine, St Louis, Missouri 63110, USA.
authors: Carlos G
authors: CG
authors: Briseño
authors: Max Planck Institute for Molecular Biomedicine, D 48149 Muenster, Germany.
authors: Saravana K
authors: 0000-0003-2658-2945
authors: SK
authors: Ramasamy
authors: Department of Nephrology and Hypertension, Hannover Medical School, D 30625 Hannover, Germany.
authors: Kashyap
authors: K
authors: Krishnasamy
authors: Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, D 30625 Hannover, Germany.
authors: Anne
authors: A
authors: Limbourg
authors: Department of Nephrology and Hypertension, Hannover Medical School, D 30625 Hannover, Germany.|Integrated Research and Treatment Center Transplantation, Hannover Medical School, D 30625 Hannover, Germany.
authors: Tamar
authors: T
authors: Kapanadze
authors: Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima University, Tokushima 770-8503, Japan.
authors: Chieko
authors: C
authors: Ishifune
authors: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, D 80336 Munich, Germany.|Medizinische Klinik I, Klinikum Rechts der Isar, Technical University of Munich, D 81675 Munich, Germany.
authors: Rabea
authors: R
authors: Hinkel
authors: Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences, ISREC, CH 1015 Lausanne, Switzerland.
authors: Freddy
authors: F
authors: Radtke
authors: Research Unit Gene Vectors, Helmholtz Zentrum München, German Research Center for Environment and Health (GmbH), D 81377 Munich, Germany.
authors: Lothar J
authors: LJ
authors: Strobl
authors: Research Unit Gene Vectors, Helmholtz Zentrum München, German Research Center for Environment and Health (GmbH), D 81377 Munich, Germany.
authors: Ursula
authors: U
authors: Zimber-Strobl
authors: Department of Cardiology, Hannover Medical School, D 30625 Hannover, Germany.
authors: L Christian
authors: LC
authors: Napp
authors: Department of Cardiology, Hannover Medical School, D 30625 Hannover, Germany.
authors: Johann
authors: J
authors: Bauersachs
authors: Department of Nephrology and Hypertension, Hannover Medical School, D 30625 Hannover, Germany.
authors: Hermann
authors: H
authors: Haller
authors: Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima University, Tokushima 770-8503, Japan.
authors: Koji
authors: K
authors: Yasutomo
authors: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, D 80336 Munich, Germany.|Medizinische Klinik I, Klinikum Rechts der Isar, Technical University of Munich, D 81675 Munich, Germany.
authors: Christian
authors: C
authors: Kupatt
authors: Department of Pathology and Immunology, Washington University in St Louis, School of Medicine, St Louis, Missouri 63110, USA.|Howard Hughes Medical Institute, Washington University in St Louis, School of Medicine, St Louis, Missouri, USA.
authors: Kenneth M
authors: KM
authors: Murphy
authors: Max Planck Institute for Molecular Biomedicine, D 48149 Muenster, Germany.
authors: Ralf H
authors: 0000-0003-3031-7677
authors: RH
authors: Adams
authors: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, D 80336 Munich, Germany.|Cardiovascular Research Institute Maastricht (CARIM), 6229 ER Maastricht, The Netherlands.
authors: Christian
authors: C
authors: Weber
authors: Department of Nephrology and Hypertension, Hannover Medical School, D 30625 Hannover, Germany.|Integrated Research and Treatment Center Transplantation, Hannover Medical School, D 30625 Hannover, Germany.
authors: Florian P
authors: 0000-0002-8313-7226
authors: FP
authors: Limbourg
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000502:physiology*; D051883:Receptor, Notch2 / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013154:Spleen / Q000166:cytology
chemical_list: D000950:Antigens, Ly; D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; C494192:Ly-6C antigen, mouse; C497764:NOTCH2 protein, human; C497765:Notch2 protein, mouse; D051883:Receptor, Notch2; D017452:Receptors, IgG; D011994:Recombinant Proteins