细胞生物学
干细胞巢
利基
生物
重编程
再生(生物学)
干细胞
体内
祖细胞
细胞
生物化学
遗传学
作者
Chao Wang,Rubén Rabadán-Ros,Paloma Martínez‐Redondo,Zaijun Ma,Lei Shi,Yuan Xue,Isabel Guillen-Guillen,Ling Huang,Tomoaki Hishida,Hsin-Kai Liao,Estrella Núñez‐Delicado,Concepción Rodrı́guez Esteban,Pedro Guillén-García,Pradeep Reddy,Juan Carlos Izpisúa Belmonte
标识
DOI:10.1038/s41467-021-23353-z
摘要
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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