Abstract
Tissue renewal and muscle regeneration largely rely on the proliferation and differentiation of muscle stem cells called muscular satellite cells (MuSCs). MuSCs are normally quiescent, but they are activated in response to various stimuli, such as inflammation. Activated MuSCs proliferate, migrate, differentiate, and fuse to form multinucleate myofibers. Meanwhile, inappropriate cues for MuSC activation induce premature differentiation and bring about stem cell loss. Recent studies revealed that stem cell regulation is disrupted in various aged tissues. We found that the expression of microRNA (miR)-155, which is an inflammation-associated miR, is upregulated in MuSCs of aged muscles, and this upregulation activates the differentiation process through suppression of C/ebpβ, which is an important molecule for maintaining MuSC self-renewal. We also found that Notch1 considerably repressed miR-155 expression, and loss of Notch1 induced miR-155 overexpression. Our findings suggest that miR-155 can act as an activator of muscular differentiation and might be responsible for accelerating aging-associated premature differentiation of MuSCs.
Highlights
Normal tissue renewal and regeneration mainly depend on the quality of tissue-resident stem cells
Muscle satellite cells (MuSCs) are myogenic stem cells required for regeneration of adult skeletal muscles
We demonstrated that miR155 is involved in activating differentiation through suppressing CCAAT/enhancer binding protein beta (C/ebpβ) expression, and that upregulation of miR-155 was partly induced by reduced Notch1 expression
Summary
Normal tissue renewal and regeneration mainly depend on the quality of tissue-resident stem cells. Muscle satellite cells (MuSCs) are myogenic stem cells required for regeneration of adult skeletal muscles. The majority of MuSCs undergo myogenic terminal differentiation and perform de novo myotube formation, or fuse with damaged myofibers to repair the injury [1, 2]. Age-related muscle wasting is characterized by the loss of muscle quantity and quality, and as well as declining numbers of MuSC [4,5,6].
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