Apr 15, 2020

Single-nucleus transcriptomics reveals functional compartmentalization in syncytial skeletal muscle cells

BioRxiv : the Preprint Server for Biology
Carmen BirchmeierM. Kim

Abstract

All cells must compartmentalize their intracellular space in order to properly function. Syncytial cells face an additional challenge to this fundamental problem, which is to coordinate gene expression programs among many nuclei. Using the skeletal muscle fiber as a model, we systematically investigated the functional heterogeneity among nuclei inside a syncytium. We performed single nucleus RNA sequencing (snRNAseq) of isolated myonuclei from uninjured and regenerating muscle, which revealed a remarkable and dynamic heterogeneity. We identified distinct nuclear subtypes unrelated to fiber type diversity, completely novel subtypes as well as the expected neuromuscular and myotendinous junction subtypes. snRNAseq of fibers from the Mdx dystrophy mouse model uncovered additional nuclear populations. Specifically, we identified the molecular signature of degenerating fibers and found a nuclear population that expressed genes implicated in myofiber repair. We confirmed the existence of this population in patients with muscular dystrophy. Finally, modifications of our approach revealed an astonishing compartmentalization inside the rare and specialized muscle spindle fibers. In summary, our work shows how regional transcription shap...Continue Reading

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Mentioned in this Paper

Study
Rhabdoviridae
Invertebrate iridescent virus 1
Virus
Sequence Determinations, RNA
RNA Viruses
Drosophila obscura
Flock house virus
Drosophila
Flaviviridae

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