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

Jaba Gamrekelashvili, Roberto Giagnorio, Jasmin Jussofie, Oliver Soehnlein, Johan Duchene, Carlos G. Briseno, Saravana K. Ramasamy, Kashyap Krishnasamy, Anne Limbourg, Tamar Kapanadze, Chieko Ishifune, Rabea Hinkel, Freddy Radtke, Lothar J. Strobl, Ursula Zimber-Strobl, L. Christian Napp, Johann Bauersachs, Hermann Haller, Koji Yasutomo, Christian KupattKenneth M. Murphy, Ralf H. Adams, Christian Weber, Florian P. Limbourg*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

73 Citations (Web of Science)

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.
Original languageEnglish
Article number12597
Number of pages14
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 31 Aug 2016

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