Macrophages provide a transient muscle stem cell niche via NAMPT secretion

被引:178
作者
Ratnayake, Dhanushika [1 ,2 ]
Nguyen, Phong D. [3 ,4 ,5 ]
Rossello, Fernando J. [1 ,6 ]
Wimmer, Verena C. [7 ,8 ]
Tan, Jean L. [1 ,2 ]
Galvis, Laura A. [1 ,10 ]
Julier, Ziad [1 ,2 ]
Wood, Alasdair J. [1 ,2 ]
Boudier, Thomas [7 ,8 ]
Isiaku, Abdulsalam I. [1 ]
Berger, Silke [1 ,2 ]
Oorschot, Viola [9 ,11 ]
Sonntag, Carmen [1 ,2 ]
Rogers, Kelly L. [7 ,8 ]
Marcelle, Christophe [1 ,10 ]
Lieschke, Graham J. [1 ]
Martino, Mikael M. [1 ,2 ]
Bakkers, Jeroen [3 ,4 ,5 ]
Currie, Peter D. [1 ,2 ]
机构
[1] Monash Univ, Australian Regenerat Med Inst, Clayton, Vic, Australia
[2] Monash Univ, EMBL Australia, Clayton, Vic, Australia
[3] Royal Netherlands Acad Arts & Sci KNAW, Hubrecht Inst, Utrecht, Netherlands
[4] Univ Med Ctr Utrecht, Utrecht, Netherlands
[5] Univ Med Ctr Utrecht, Dept Med Physiol, Div Heart & Lungs, Utrecht, Netherlands
[6] Univ Melbourne, Ctr Canc Res, Melbourne, Vic, Australia
[7] Walter & Eliza Hall Inst Med Res, Parkville, Vic, Australia
[8] Univ Melbourne, Dept Med Biol, Parkville, Vic, Australia
[9] Monash Univ, Monash Ramaciotti Ctr Cryo Electron Microscopy, Melbourne, Vic, Australia
[10] Univ Claude Bernard Lyon 1, Inst NeuroMyoGene INMG, CNRS UMR 5310, INSERM U1217, Lyon, France
[11] European Mol Biol Lab, Electron Microscopy Core Facil, Heidelberg, Germany
基金
英国医学研究理事会;
关键词
SKELETAL-MUSCLE; TRANSGENIC ZEBRAFISH; PROGENITOR CELLS; MYOGENIC CELLS; BETA-CELLS; DYNAMICS; MODEL; DIFFERENTIATION; QUANTIFICATION; PROLIFERATION;
D O I
10.1038/s41586-021-03199-7
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Skeletal muscle regenerates through the activation of resident stem cells. Termed satellite cells, these normally quiescent cells are induced to proliferate by wound-derived signals(1). 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.
引用
收藏
页码:281 / +
页数:34
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