| First Author | Dos Santos M | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 4333 |
| PubMed ID | 37468485 | Mgi Jnum | J:338268 |
| Mgi Id | MGI:7511652 | Doi | 10.1038/s41467-023-40073-8 |
| Citation | Dos Santos M, et al. (2023) Opposing gene regulatory programs governing myofiber development and maturation revealed at single nucleus resolution. Nat Commun 14(1):4333 |
| abstractText | 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 Ca(2+) 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. |
