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Opposing gene regulatory programs governing myofiber development and maturation revealed at single nucleus resolution

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  • Matthieu Dos Santos

    (University of Texas Southwestern Medical Center)

  • Akansha M. Shah

    (University of Texas Southwestern Medical Center)

  • Yichi Zhang

    (University of Texas Southwestern Medical Center)

  • Svetlana Bezprozvannaya

    (University of Texas Southwestern Medical Center)

  • Kenian Chen

    (University of Texas Southwestern Medical Center)

  • Lin Xu

    (University of Texas Southwestern Medical Center)

  • Weichun Lin

    (University of Texas Southwestern Medical Center)

  • John R. McAnally

    (University of Texas Southwestern Medical Center)

  • Rhonda Bassel-Duby

    (University of Texas Southwestern Medical Center)

  • Ning Liu

    (University of Texas Southwestern Medical Center)

  • Eric N. Olson

    (University of Texas Southwestern Medical Center)

Abstract

Skeletal muscle fibers express distinct gene programs during development and maturation, but the underlying gene regulatory networks that confer stage-specific myofiber properties remain unknown. To decipher these distinctive gene programs and how they respond to neural activity, we generated a combined multi-omic single-nucleus RNA-seq and ATAC-seq atlas of mouse skeletal muscle development at multiple stages of embryonic, fetal, and postnatal life. We found that Myogenin, Klf5, and Tead4 form a transcriptional complex that synergistically activates the expression of muscle genes in developing myofibers. During myofiber maturation, the transcription factor Maf acts as a transcriptional switch to activate the mature fast muscle gene program. In skeletal muscles of mutant mice lacking voltage-gated L-type Ca2+ channels (Cav1.1), Maf expression and myofiber maturation are impaired. These findings provide a transcriptional atlas of muscle development and reveal genetic links between myofiber formation, maturation, and contraction.

Suggested Citation

  • Matthieu Dos Santos & Akansha M. Shah & Yichi Zhang & Svetlana Bezprozvannaya & Kenian Chen & Lin Xu & Weichun Lin & John R. McAnally & Rhonda Bassel-Duby & Ning Liu & Eric N. Olson, 2023. "Opposing gene regulatory programs governing myofiber development and maturation revealed at single nucleus resolution," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40073-8
    DOI: 10.1038/s41467-023-40073-8
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