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Updated: May 16, 2026

Identification and Analysis of Myogenic Progenitors In Vivo During Acute Skeletal Muscle Injury by High-Dimensional Single-Cell Mass Cytometry
Published on: December 1, 2023
Differentially activated macrophages orchestrate myogenic precursor cell fate during human skeletal muscle
Marielle Saclier1, Houda Yacoub-Youssef, Abigail L Mackey
1INSERM, U1016, Institut Cochin, Paris, France.
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.
Insights
Macrophages (MPs) sequentially orchestrate skeletal muscle regeneration by differentially regulating myogenic precursor cells (MPCs). Pro-inflammatory MPs initially inhibit MPC fusion, while anti-inflammatory MPs later promote MPC differentiation and myotube formation.
Area of Science:
- Cell Biology
- Immunology
- Regenerative Medicine
Background:
- Macrophages (MPs) play a dual role in tissue repair, influencing outcomes based on their activation state.
- MPs are critical for adult skeletal muscle repair, interacting with myogenic precursor cells (MPCs).
- The precise mechanisms of MP-MPC interactions in human skeletal muscle regeneration remain incompletely understood.
Purpose of the Study:
- To investigate the in vitro and in vivo interactions between differentially activated human MPs and MPCs during skeletal muscle regeneration.
- To elucidate the sequential roles of MPs in orchestrating adult myogenesis.
Main Methods:
- In vitro co-culture systems to assess MP-MPC interactions.
- In vivo analysis of regenerating human skeletal muscle tissue.
- Assessment of cytokine/growth factor secretion by MPs.
- Evaluation of MPC proliferation, differentiation, and myotube formation.
- Immunohistochemical analysis of myogenic and MP markers in regenerating muscle.
Main Results:
- In vitro, pro-inflammatory MPs inhibited MPC fusion, whereas anti-inflammatory MPs promoted MPC differentiation and myotube maturation.
- In vivo, proliferating MPCs in regenerating muscle were associated with pro-inflammatory MPs.
- Differentiating myogenin-positive MPCs were preferentially coupled with anti-inflammatory MPs.
- Demonstrated a sequential orchestration of myogenesis by MPs during skeletal muscle regeneration in humans.
Conclusions:
- Human macrophages sequentially regulate adult myogenesis during skeletal muscle regeneration.
- MP activation state critically influences MPC fate, controlling skeletal muscle repair.
- Inflammation, mediated by MP polarization, is a key regulator of stem cell behavior and tissue repair coordination.
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