RT Journal Article
SR Electronic
T1 Macrophages provide a transient muscle stem cell niche via NAMPT secretion
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.24.262428
DO 10.1101/2020.08.24.262428
A1 Dhanushika Ratnayake
A1 Phong D. Nguyen
A1 Fernando J. Rossello
A1 Verena C. Wimmer
A1 Abdulsalam I. Isiaku
A1 Laura A. Galvis
A1 Alasdair J. Wood
A1 Ziad Julier
A1 Thomas Boudier
A1 Viola Oorschot
A1 Kelly L. Rogers
A1 Mikaël M. Martino
A1 Christophe Marcelle
A1 Graham J. Lieschke
A1 Jeroen Bakkers
A1 Peter D. Currie
YR 2020
UL http://biorxiv.org/content/early/2020/08/24/2020.08.24.262428.abstract
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.