151. Single-nucleus RNA-seq and FISH identify coordinated transcriptional activity in mammalian myofibers.
- Author
-
Dos Santos M, Backer S, Saintpierre B, Izac B, Andrieu M, Letourneur F, Relaix F, Sotiropoulos A, and Maire P
- Subjects
- Animals, Female, Mice, Inbred C57BL, Muscle, Skeletal cytology, Muscle, Skeletal embryology, Muscle, Skeletal growth & development, Myosin Heavy Chains genetics, Neuromuscular Junction cytology, Single-Cell Analysis, Tendons cytology, Transcription, Genetic, Cell Nucleus genetics, Gene Expression Regulation, In Situ Hybridization, Fluorescence methods, Muscle Fibers, Skeletal cytology, Muscle Fibers, Skeletal physiology, Sequence Analysis, RNA methods
- Abstract
Skeletal muscle fibers are large syncytia but it is currently unknown whether gene expression is coordinately regulated in their numerous nuclei. Here we show by snRNA-seq and snATAC-seq 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 show 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 previously undefined mechanism of coordination of gene expression in a syncytium. more...
- Published
- 2020
- Full Text
- View/download PDF