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

Matthieu Dos Santos, Akansha M. Shah, Yichi Zhang, Svetlana Bezprozvannaya, Kenian Chen, Lin Xu, Weichun Lin, John R. McAnally, Rhonda Bassel-Duby, Ning Liu and Eric N. Olson ()
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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

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: 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.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40073-8

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DOI: 10.1038/s41467-023-40073-8

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