In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche
| Autor: | Concepcion Rodriguez Esteban, Juan Carlos Izpisua Belmonte, Ruben Rabadan Ros, Pedro Guillén-García, Tomoaki Hishida, Pradeep Reddy, Ling Huang, Yuan Xue, Hsin Kai Liao, Isabel Guillen-Guillen, Lei Shi, Chao Wang, Zaijun Ma, Paloma Martinez-Redondo, Estrella Nuñez Delicado |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cell biology Satellite Cells Skeletal Muscle Science Kruppel-Like Transcription Factors General Physics and Astronomy Gene Expression Mice Transgenic Biology General Biochemistry Genetics and Molecular Biology Article Proto-Oncogene Proteins c-myc Mesoderm 03 medical and health sciences Kruppel-Like Factor 4 0302 clinical medicine SOX2 Downregulation and upregulation Myofibrils In vivo Wnt4 Protein WNT4 Muscle stem cells Animals Regeneration Stem Cell Niche Cells Cultured Multidisciplinary SOXB1 Transcription Factors Biological techniques Cell Differentiation General Chemistry Cellular Reprogramming Stem-cell research 030104 developmental biology KLF4 Female sense organs Stem cell Reprogramming Cell aging Octamer Transcription Factor-3 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Short term systemic expression of the reprogramming factors Oct-3/4, Sox2, Klf4, c-Myc (OSKM) rejuvenates aging cells and promotes tissue regeneration. Here the authors show that myofiber-specific expression of OSKM accelerates muscle regeneration by reducing secretion of muscle stem cell quiescence promoting Wnt4. |
| Databáze: | OpenAIRE |
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