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Publication : In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche.

First Author  Wang C Year  2021
Journal  Nat Commun Volume  12
Issue  1 Pages  3094
PubMed ID  34035273 Mgi Jnum  J:340383
Mgi Id  MGI:6713964 Doi  10.1038/s41467-021-23353-z
Citation  Wang C, et al. (2021) In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche. Nat Commun 12(1):3094
abstractText  Short-term, systemic expression of the Yamanaka reprogramming factors (Oct-3/4, Sox2, Klf4 and c-Myc [OSKM]) has been shown to rejuvenate aging cells and promote tissue regeneration in vivo. However, the mechanisms by which OSKM promotes tissue regeneration are unknown. In this work, we focus on a specific tissue and demonstrate that local expression of OSKM, specifically in myofibers, induces the activation of muscle stem cells or satellite cells (SCs), which accelerates muscle regeneration in young mice. In contrast, expressing OSKM directly in SCs does not improve muscle regeneration. Mechanistically, expressing OSKM in myofibers regulates the expression of genes important for the SC microenvironment, including upregulation of p21, which in turn downregulates Wnt4. This is critical because Wnt4 is secreted by myofibers to maintain SC quiescence. Thus, short-term induction of the Yamanaka factors in myofibers may promote tissue regeneration by modifying the stem cell niche.
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