After birth, primary and secondary myofibers mature and grow extensively by synthesizing new proteins and fusing with myoblasts to reach their mature adult size 2. Like hematopoiesis, myogenesis occurs in successive phases, starting from formation of primary myofibers during embryogenesis to secondary myofibers during the fetal period. Myofibers are formed by differentiation of muscle stem cells (MuSCs) into myoblasts, which undergo fusion to form multinucleated myofibers 1. Skeletal muscle is mainly composed of myofibers, which are large contractile cell syncytia containing tens to thousands of nuclei. Skeletal muscle is the largest tissue in the body, and is essential for locomotion, posture, body temperature regulation, and glucose and amino acid storage. These findings provide a transcriptional atlas of muscle development and reveal genetic links between myofiber formation, maturation, and contraction. In skeletal muscles of mutant mice lacking voltage-gated L-type Ca 2+ channels (Cav1.1), Maf expression and myofiber maturation are impaired. During myofiber maturation, the transcription factor Maf acts as a transcriptional switch to activate the mature fast muscle gene program. We found that Myogenin, Klf5, and Tead4 form a transcriptional complex that synergistically activates the expression of muscle genes in developing myofibers. 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. ![]() 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.
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