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

Author

Listed:
  • Chao Wang

    (Gene Expression Laboratory, Salk Institute for Biological Studies)

  • Ruben Rabadan Ros

    (Gene Expression Laboratory, Salk Institute for Biological Studies)

  • Paloma Martinez-Redondo

    (Gene Expression Laboratory, Salk Institute for Biological Studies)

  • Zaijun Ma

    (Gene Expression Laboratory, Salk Institute for Biological Studies)

  • Lei Shi

    (Gene Expression Laboratory, Salk Institute for Biological Studies)

  • Yuan Xue

    (Gene Expression Laboratory, Salk Institute for Biological Studies)

  • Isabel Guillen-Guillen

    (Gene Expression Laboratory, Salk Institute for Biological Studies)

  • Ling Huang

    (Integrative Genomics and Bioinformatics Core, Salk Institute for Biological Studies)

  • Tomoaki Hishida

    (Gene Expression Laboratory, Salk Institute for Biological Studies)

  • Hsin-Kai Liao

    (Gene Expression Laboratory, Salk Institute for Biological Studies)

  • Estrella Nuñez Delicado

    (Universidad Católica San Antonio de Murcia (UCAM), Campus de los Jerónimos)

  • Concepcion Rodriguez Esteban

    (Gene Expression Laboratory, Salk Institute for Biological Studies)

  • Pedro Guillen-Garcia

    (Department of Traumatology and Research Unit, Clinica CEMTRO)

  • Pradeep Reddy

    (Gene Expression Laboratory, Salk Institute for Biological Studies)

  • Juan Carlos Izpisua Belmonte

    (Gene Expression Laboratory, Salk Institute for Biological Studies)

Abstract

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.

Suggested Citation

  • Chao Wang & Ruben Rabadan Ros & Paloma Martinez-Redondo & Zaijun Ma & Lei Shi & Yuan Xue & Isabel Guillen-Guillen & Ling Huang & Tomoaki Hishida & Hsin-Kai Liao & Estrella Nuñez Delicado & Concepcion , 2021. "In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23353-z
    DOI: 10.1038/s41467-021-23353-z
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    Cited by:

    1. Ali Doğa Yücel & Vadim N. Gladyshev, 2024. "The long and winding road of reprogramming-induced rejuvenation," Nature Communications, Nature, vol. 15(1), pages 1-9, December.

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