Congratulations to the RELAIX team for publishing an article in Embo Reports on the essential role of progressive muscle reoxygenation after transient hypoxia in coordinating myogenesis and skeletal muscle repair via modulation of REV-ERBα expression.

Muscle stem cells (MuSCs) are essential for skeletal muscle repair. After injury, MuSCs activate in a low-oxygen environment until muscle fibers and vascularization are restored. The dynamics of oxygenation in skeletal muscle during regeneration, and its impact on the fate of MuSCs, have been little studied.
Our results confirm that muscle repair begins in a hypoxic environment and is accompanied by gradual reoxygenation. Interestingly, when reoxygenation of skeletal muscle is delayed by keeping mice in a hypoxic chamber (10% oxygen inhaled), muscle repair is impaired, leading to the formation of hypotrophic muscle fibers.
We show that prolonged hypoxia decreases the ability of MuSCs to differentiate and fuse, independently of HIF-1α and HIF-2α. From a mechanistic point of view, our results indicate that systemic hypoxia specifically affects the circadian clock of MuSCs by increasing the expression of REV-ERBα. Using pharmacological tools, we demonstrate that REV-ERBα negatively regulates myogenesis by reducing late myogenic fusion under conditions of prolonged hypoxia.
Thus, our work highlights the essential role of progressive muscle reoxygenation after transient hypoxia in coordinating myogenesis and skeletal muscle repair via modulation of REV-ERBα expression.

 

Transient hypoxia followed by progressive reoxygenation is required for muscle repair
Embo Reports Volume 27, pages 954–974, (2026)

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