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Runx1 Transcription Factor Is Required for Myoblasts Proliferation during Muscle Regeneration


In response to muscle injury, the muscle initiates a repair process that calls for the proliferation of muscle stem cells, which differentiate and fuse to create the myofibers that regenerate the tissue. Maintaining the balance between myoblast proliferation and differentiation is crucial for proper regeneration, with disruption leading to impaired regeneration characteristic of muscle-wasting diseases. Our study highlights the important role the Runx1 transcription factor plays in muscle regeneration and in regulating the balance between muscle stem cell proliferation and differentiation. While not expressed in healthy muscle tissue, Runx1 level significantly increases in response to various types of muscle damage. This aligns with our finding that mice lacking Runx1 in their muscles suffer from impaired muscle regeneration. Their muscles contained a significantly low number of regenerating myofibers, which were also relatively smaller in size, resulting in loss of muscle mass and motor capabilities. Our results indicate that Runx1 regulates muscle regeneration by preventing premature differentiation of proliferating myoblasts, thereby facilitating the buildup of the myoblast pool required for proper regeneration. Through genome-wide gene-expression analysis we identify a set of Runx1-regulated genes responsible for muscle regeneration thereby implicating Runx1 in the pathology of muscle wasting diseases such as Duchenne muscular dystrophy.


Vyšlo v časopise: Runx1 Transcription Factor Is Required for Myoblasts Proliferation during Muscle Regeneration. PLoS Genet 11(8): e32767. doi:10.1371/journal.pgen.1005457
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005457

Souhrn

In response to muscle injury, the muscle initiates a repair process that calls for the proliferation of muscle stem cells, which differentiate and fuse to create the myofibers that regenerate the tissue. Maintaining the balance between myoblast proliferation and differentiation is crucial for proper regeneration, with disruption leading to impaired regeneration characteristic of muscle-wasting diseases. Our study highlights the important role the Runx1 transcription factor plays in muscle regeneration and in regulating the balance between muscle stem cell proliferation and differentiation. While not expressed in healthy muscle tissue, Runx1 level significantly increases in response to various types of muscle damage. This aligns with our finding that mice lacking Runx1 in their muscles suffer from impaired muscle regeneration. Their muscles contained a significantly low number of regenerating myofibers, which were also relatively smaller in size, resulting in loss of muscle mass and motor capabilities. Our results indicate that Runx1 regulates muscle regeneration by preventing premature differentiation of proliferating myoblasts, thereby facilitating the buildup of the myoblast pool required for proper regeneration. Through genome-wide gene-expression analysis we identify a set of Runx1-regulated genes responsible for muscle regeneration thereby implicating Runx1 in the pathology of muscle wasting diseases such as Duchenne muscular dystrophy.


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