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

Minchul Kim, Vedran Franke, Bettina Brandt, Simone Spuler, Altuna Akalin, Carmen Birchmeier
2020 bioRxiv   pre-print
AbstractAll cells must compartmentalize their intracellular space in order to properly function1. 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
more » ... ing 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 neuromuscular2-5 and myotendinous6-8 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 shapes the architecture of multinucleated syncytial muscle cells, and provides an unprecedented roadmap to molecularly dissect distinct compartments of the muscle.
doi:10.1101/2020.04.14.041665 fatcat:woqygjjah5amjopbfag4mn6bpy