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 zebrafish 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 specific subset of macrophages ‘dwell’ within the injury, establishing a transient but obligate niche for stem cell proliferation. Single-cell profiling identified 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. This analysis shows that in addition to their ability to modulate the immune response, specific macrophage populations also provide a transient stem-cell-activating niche, directly supplying proliferation-inducing cues that govern the repair process that is mediated by muscle stem cells. This study demonstrates that macrophage-derived niche signals for muscle stem cells, such as NAMPT, can be applied as new therapeutic modalities for skeletal muscle injury and disease.

骨骼肌通过常驻干细胞的激活而再生。这些通常处于静止状态的细胞被称为卫星细胞，它们被伤口衍生信号诱导增殖¹. 由于无法可视化伤口内发生的复杂细胞相互作用，因此无法识别这些线索的来源和性质。在这里，我们使用斑马鱼的肌肉损伤模型，在整个修复过程中实时、系统地捕捉损伤后卫星细胞与先天免疫系统之间的相互作用。该分析表明，特定的巨噬细胞亚群“驻留在”损伤内，为干细胞增殖建立了一个短暂但必不可少的生态位。单细胞分析鉴定了巨噬细胞分泌的增殖信号，其中包括细胞因子烟酰胺磷酸核糖转移酶（Nampt，在人类中也称为内脂素或 PBEF）。肌肉再生需要巨噬细胞生态位分泌 Nampt，通过在肌肉干细胞上表达的 CC 基序趋化因子受体 5 (Ccr5) 起作用。该分析表明，除了调节免疫反应的能力外，特定的巨噬细胞群还提供了一个短暂的干细胞激活生态位，直接提供增殖诱导信号，控制由肌肉干细胞介导的修复过程。这项研究表明，巨噬细胞衍生的肌肉干细胞利基信号，如 NAMPT，可用作骨骼肌损伤和疾病的新治疗方式。直接提供增殖诱导信号，控制由肌肉干细胞介导的修复过程。这项研究表明，巨噬细胞衍生的肌肉干细胞利基信号，如 NAMPT，可用作骨骼肌损伤和疾病的新治疗方式。直接提供增殖诱导信号，控制由肌肉干细胞介导的修复过程。这项研究表明，巨噬细胞衍生的肌肉干细胞利基信号，如 NAMPT，可用作骨骼肌损伤和疾病的新治疗方式。