title: Differentially activated macrophages orchestrate myogenic precursor cell fate during human skeletal muscle regeneration.
abstract: Macrophages (MPs) exert either beneficial or deleterious effects on tissue repair, depending on their activation/polarization state. They are crucial for adult skeletal muscle repair, notably by acting on myogenic precursor cells. However, these interactions have not been fully characterized. Here, we explored both in vitro and in vivo, in human, the interactions of differentially activated MPs with myogenic precursor cells (MPCs) during adult myogenesis and skeletal muscle regeneration. We showed in vitro that through the differential secretion of cytokines and growth factors, proinflammatory MPs inhibited MPC fusion while anti-inflammatory MPs strongly promoted MPC differentiation by increasing their commitment into differentiated myocytes and the formation of mature myotubes. Furthermore, the in vivo time course of expression of myogenic and MP markers was studied in regenerating human healthy muscle after damage. We observed that regenerating areas containing proliferating MPCs were preferentially associated with MPs expressing proinflammatory markers. In the same muscle, regenerating areas containing differentiating myogenin-positive MPCs were preferentially coupled to MPs harboring anti-inflammatory markers. These data demonstrate for the first time in human that MPs sequentially orchestrate adult myogenesis during regeneration of damaged skeletal muscle. These results support the emerging concept that inflammation, through MP activation, controls stem cell fate and coordinates tissue repair.
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France.
authors.forename: Marielle
authors.initials: M
authors.lastname: Saclier
authors.forename: Houda
authors.initials: H
authors.lastname: Yacoub-Youssef
authors.forename: Abigail L
authors.initials: AL
authors.lastname: Mackey
authors.forename: Ludovic
authors.initials: L
authors.lastname: Arnold
authors.forename: Hamida
authors.initials: H
authors.lastname: Ardjoune
authors.forename: Mélanie
authors.initials: M
authors.lastname: Magnan
authors.forename: Frédéric
authors.initials: F
authors.lastname: Sailhan
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
authors.forename: Grace K
authors.initials: GK
authors.lastname: Pavlath
authors.forename: Rémi
authors.initials: R
authors.lastname: Mounier
authors.forename: Michael
authors.initials: M
authors.lastname: Kjaer
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Chazaud
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007249:Inflammation; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000145:classification / Q000166:cytology* / Q000378:metabolism; D024510:Muscle Development / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D018008:Myogenin