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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Antigens, Ly / metabolism
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Bone Marrow Cells / metabolism
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Calcium-Binding Proteins
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Cell Differentiation
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Cells, Cultured
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Endothelial Cells / metabolism
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GPI-Linked Proteins / metabolism
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Healthy Volunteers
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Humans
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / metabolism*
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Male
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Mice
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Mice, Knockout
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Monocytes / physiology*
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Receptor, Notch2 / metabolism*
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Receptors, IgG / metabolism
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Recombinant Proteins / metabolism
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Signal Transduction / physiology*
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Spleen / cytology
Substances
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Antigens, Ly
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Calcium-Binding Proteins
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Dlk1 protein, mouse
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FCGR3B protein, human
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GPI-Linked Proteins
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Intercellular Signaling Peptides and Proteins
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Ly-6C antigen, mouse
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NOTCH2 protein, human
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Notch2 protein, mouse
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Receptor, Notch2
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Receptors, IgG
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Recombinant Proteins