PT - JOURNAL ARTICLE AU - Matthieu Dos Santos AU - Stéphanie Backer AU - Benjamin Saintpierre AU - Frederic Relaix AU - Athanassia Sotiropoulos AU - Pascal Maire TI - Single-nucleus RNA-seq and FISH reveal coordinated transcriptional activity in mammalian myofibers AID - 10.1101/2020.04.16.043620 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.04.16.043620 4099 - http://biorxiv.org/content/early/2020/04/16/2020.04.16.043620.short 4100 - http://biorxiv.org/content/early/2020/04/16/2020.04.16.043620.full AB - Skeletal muscle fibers are large syncytia but it is currently unknown whether gene expression is coordinately regulated in their numerous nuclei. By snRNA-seq and snATAC-seq, we showed that slow, fast, myotendinous and neuromuscular junction myonuclei each have different transcriptional programs, associated with distinct chromatin states and combinations of transcription factors. In adult mice, identified myofiber types predominantly express either a slow or one of the three fast isoforms of Myosin heavy chain (MYH) proteins, while a small number of hybrid fibers can express more than one MYH. By snRNA-seq and FISH, we showed that the majority of myonuclei within a myofiber are synchronized, coordinately expressing only one fast Myh isoform with a preferential panel of muscle-specific genes. Importantly, this coordination of expression occurs early during post-natal development and depends on innervation. These findings highlight a unique mechanism of coordination of gene expression in a syncytium.Competing Interest StatementThe authors have declared no competing interest.