Single-nucleus RNA-seq and FISH identify coordinated transcriptional activity in mammalian myofibers

Matthieu Santos, Stéphanie Backer, Benjamin Saintpierre, Brigitte Izac, Muriel Andrieu, Franck Letourneur, Frederic Relaix, Athanassia Sotiropoulos and Pascal Maire ()
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Matthieu Santos: Université de Paris, Institut Cochin, INSERM, CNRS.
Stéphanie Backer: Université de Paris, Institut Cochin, INSERM, CNRS.
Benjamin Saintpierre: Université de Paris, Institut Cochin, INSERM, CNRS.
Brigitte Izac: Université de Paris, Institut Cochin, INSERM, CNRS.
Muriel Andrieu: Université de Paris, Institut Cochin, INSERM, CNRS.
Franck Letourneur: Université de Paris, Institut Cochin, INSERM, CNRS.
Frederic Relaix: Université Paris-Est Creteil, INSERM U955 IMRB.
Athanassia Sotiropoulos: Université de Paris, Institut Cochin, INSERM, CNRS.
Pascal Maire: Université de Paris, Institut Cochin, INSERM, CNRS.

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18789-8

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DOI: 10.1038/s41467-020-18789-8

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