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

Author

Listed:
  • 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
    Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center
    University of Cincinnati College of Medicine)

  • Nathan Salomonis

    (Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center
    University of Cincinnati College of Medicine)

  • Douglas P. Millay

    (Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center
    University of Cincinnati College of Medicine)

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.

Suggested Citation

  • Michael J. Petrany & Casey O. Swoboda & Chengyi Sun & Kashish Chetal & Xiaoting Chen & Matthew T. Weirauch & Nathan Salomonis & Douglas P. Millay, 2020. "Single-nucleus RNA-seq identifies transcriptional heterogeneity in multinucleated skeletal myofibers," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-20063-w
    DOI: 10.1038/s41467-020-20063-w
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    Cited by:

    1. Hongchun Lin & Hui Peng & Yuxiang Sun & Meijun Si & Jiao Wu & Yanlin Wang & Sandhya S. Thomas & Zheng Sun & Zhaoyong Hu, 2023. "Reprogramming of cis-regulatory networks during skeletal muscle atrophy in male mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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