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

Minchul Kim, Vedran Franke, Bettina Brandt, Elijah D. Lowenstein, Verena Schöwel, Simone Spuler, Altuna Akalin () and Carmen Birchmeier ()
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Minchul Kim: Developmental Biology/Signal Transduction, Max Delbrueck Center for Molecular Medicine
Vedran Franke: Berlin Institute for Medical Systems Biology, Max Delbrueck Center for Molecular Medicine
Bettina Brandt: Developmental Biology/Signal Transduction, Max Delbrueck Center for Molecular Medicine
Elijah D. Lowenstein: Developmental Biology/Signal Transduction, Max Delbrueck Center for Molecular Medicine
Verena Schöwel: Muscle Research Unit, Experimental and Clinical Research Center, Charité Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine
Simone Spuler: Muscle Research Unit, Experimental and Clinical Research Center, Charité Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine
Altuna Akalin: Berlin Institute for Medical Systems Biology, Max Delbrueck Center for Molecular Medicine
Carmen Birchmeier: Developmental Biology/Signal Transduction, Max Delbrueck Center for Molecular Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Syncytial skeletal muscle cells contain hundreds of nuclei in a shared cytoplasm. We investigated nuclear heterogeneity and transcriptional dynamics in the uninjured and regenerating muscle using single-nucleus RNA-sequencing (snRNAseq) of isolated nuclei from muscle fibers. This revealed distinct nuclear subtypes unrelated to fiber type diversity, previously unknown subtypes as well as the expected ones at the neuromuscular and myotendinous junctions. In fibers of the Mdx dystrophy mouse model, distinct subtypes emerged, among them nuclei expressing a repair signature that were also abundant in the muscle of dystrophy patients, and a nuclear population associated with necrotic fibers. Finally, modifications of our approach revealed the compartmentalization in the rare and specialized muscle spindle. Our data identifies nuclear compartments of the myofiber and defines a molecular roadmap for their functional analyses; the data can be freely explored on the MyoExplorer server ( https://shiny.mdc-berlin.de/MyoExplorer/ ).

Date: 2020
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DOI: 10.1038/s41467-020-20064-9

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