PT  - JOURNAL ARTICLE
AU  - Dhanushika Ratnayake
AU  - Phong D. Nguyen
AU  - Fernando J. Rossello
AU  - Verena C. Wimmer
AU  - Abdulsalam I. Isiaku
AU  - Laura A. Galvis
AU  - Alasdair J. Wood
AU  - Ziad Julier
AU  - Thomas Boudier
AU  - Viola Oorschot
AU  - Kelly L. Rogers
AU  - Mikaël M. Martino
AU  - Christophe Marcelle
AU  - Graham J. Lieschke
AU  - Jeroen Bakkers
AU  - Peter D. Currie
TI  - Macrophages provide a transient muscle stem cell niche via NAMPT secretion
AID  - 10.1101/2020.08.24.262428
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.08.24.262428
4099  - http://biorxiv.org/content/early/2020/08/24/2020.08.24.262428.short
4100  - http://biorxiv.org/content/early/2020/08/24/2020.08.24.262428.full
AB  - Skeletal muscle is paradigmatic of a regenerative tissue that repairs itself via the activation of a resident stem cell1. Termed the satellite cell, these normally quiescent cells are induced to proliferate by ill-defined wound-derived signals2. Identifying the source and nature of these pro-regenerative cues has been hampered by an inability to visualise the complex cellular interactions that occur within the wound environment. We therefore developed a zebrafish muscle injury model to systematically capture satellite cell interactions within the injury site, in real time, throughout the repair process. This analysis identified that a specific subset of macrophages ‘dwells’ within the injury, establishing a transient but obligate stem cell niche required for stem cell proliferation. Single cell profiling identified specific signals secreted from dwelling macrophages that include the cytokine, Nicotinamide phosphoribosyltransferase (NAMPT/Visfatin/PBEF). Here we show that NAMPT secretion from the macrophage niche is required for muscle regeneration, acting through the C-C motif chemokine receptor type 5 (CCR5) expressed on muscle stem cells. This analysis reveals that along with their well-described ability to modulate the pro-inflammatory and anti-inflammatory phases of wound repair, specific macrophage populations also provide a transient stem cell-activating niche, directly supplying pro-proliferative cues that govern the timing and rate of muscle stem cell-mediated repair processes.Competing Interest StatementPeter D. Currie, Mikaël M. Martino and Dhanushika Ratnayake through Monash University have filed a patent application on the use of NAMPT.