Single-nucleus RNA-seq and FISH identify coordinated transcriptional activity in mammalian myofibers.
Matthieu Dos SantosStéphanie BackerBenjamin SaintpierreBrigitte IzacMuriel AndrieuFranck LetourneurFrederic RelaixAthanassia SotiropoulosPascal MairePublished in: Nature communications (2020)
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.
Keyphrases
- rna seq
- gene expression
- transcription factor
- skeletal muscle
- single cell
- hypertrophic cardiomyopathy
- dna methylation
- genome wide
- genome wide identification
- binding protein
- poor prognosis
- left ventricular
- south africa
- insulin resistance
- public health
- dna binding
- high fat diet induced
- wild type
- type diabetes
- heart failure
- dna damage
- oxidative stress
- childhood cancer
- young adults