Single-nucleus RNA-seq identifies transcriptional heterogeneity in multinucleated skeletal myofibers

Michael J. Petrany, Casey O. Swoboda, Chengyi Sun, Kashish Chetal, Xiaoting Chen, Matthew T. Weirauch, Nathan Salomonis and Douglas P. Millay ()
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Michael J. Petrany: Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center
Casey O. Swoboda: Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center
Chengyi Sun: Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center
Kashish Chetal: Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center
Xiaoting Chen: Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center
Matthew T. Weirauch: Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center
Nathan Salomonis: Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center
Douglas P. Millay: Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract While the majority of cells contain a single nucleus, cell types such as trophoblasts, osteoclasts, and skeletal myofibers require multinucleation. One advantage of multinucleation can be the assignment of distinct functions to different nuclei, but comprehensive interrogation of transcriptional heterogeneity within multinucleated tissues has been challenging due to the presence of a shared cytoplasm. Here, we utilized single-nucleus RNA-sequencing (snRNA-seq) to determine the extent of transcriptional diversity within multinucleated skeletal myofibers. Nuclei from mouse skeletal muscle were profiled across the lifespan, which revealed the presence of distinct myonuclear populations emerging in postnatal development as well as aging muscle. Our datasets also provided a platform for discovery of genes associated with rare specialized regions of the muscle cell, including markers of the myotendinous junction and functionally validated factors expressed at the neuromuscular junction. These findings reveal that myonuclei within syncytial muscle fibers possess distinct transcriptional profiles that regulate muscle biology.

Date: 2020
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DOI: 10.1038/s41467-020-20063-w

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