Macrophages Provide a Transient Muscle Stem Cell Niche Via NAMPT Secretion
Article Macrophages provide a transient muscle stem cell niche via NAMPT secretion https://doi.org/10.1038/s41586-021-03199-7 Dhanushika Ratnayake1,2, Phong D. Nguyen3,4,11, Fernando J. Rossello1,5,11, Verena C. Wimmer6,7,11, Jean L. Tan1,2,11, Laura A. Galvis1,9, Ziad Julier1,2, Alasdair J. Wood1,2, Received: 20 June 2019 Thomas Boudier6,7, Abdulsalam I. Isiaku1, Silke Berger1,2, Viola Oorschot8,10, Accepted: 7 January 2021 Carmen Sonntag1,2, Kelly L. Rogers6,7, Christophe Marcelle1,9, Graham J. Lieschke1, Mikaël M. Martino1,2,12, Jeroen Bakkers3,4,12 .& Peter D Currie1,2 ✉ Published online: xx xx xxxx Check for updates Skeletal muscle regenerates through the activation of resident stem cells. Termed satellite cells, these normally quiescent cells are induced to proliferate by wound-derived signals1. Identifying the source and nature of these cues has been hampered by an inability to visualize the complex cell interactions that occur within the wound. Here we use muscle injury models in zebrafsh to systematically capture the interactions between satellite cells and the innate immune system after injury, in real time, throughout the repair process. This analysis revealed that a specifc subset of macrophages ‘dwell’ within the injury, establishing a transient but obligate niche for stem cell proliferation. Single-cell profling identifed proliferative signals that are secreted by dwelling macrophages, which include the cytokine nicotinamide phosphoribosyltransferase (Nampt, which is also known as visfatin or PBEF in humans). Nampt secretion from the macrophage niche is required for muscle regeneration, acting through the C-C motif chemokine receptor type 5 (Ccr5), which is expressed on muscle stem cells.
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