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Single-nucleus RNA-seq and FISH identify coordinated transcriptional activity in mammalian myofibers.
Single-nucleus RNA-seq and FISH identify coordinated transcriptional activity in mammalian myofibers.
- Source :
-
Nature communications [Nat Commun] 2020 Oct 09; Vol. 11 (1), pp. 5102. Date of Electronic Publication: 2020 Oct 09. - Publication Year :
- 2020
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 33037211
- Full Text :
- https://doi.org/10.1038/s41467-020-18789-8