Transcriptomic gene signatures measure satellite cell activity in muscular dystrophies
Elise N. Engquist,
Anna Greco,
Leo A.B. Joosten,
Baziel G.M. van Engelen,
Christopher R.S. Banerji,
Peter S. Zammit
Affiliations
Elise N. Engquist
King’s College London, Randall Centre for Cell and Molecular Biophysics, New Hunt’s House, Guy’s Campus, London SE1 1UL, UK
Anna Greco
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen 6525 GA, the Netherlands; Department of Internal Medicine, Radboud Institute of Molecular Life Sciences (RIMLS) and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, Geert Grooteplein Zuid 10, Nijmegen 6525 GA, The Netherlands
Leo A.B. Joosten
Department of Internal Medicine, Radboud Institute of Molecular Life Sciences (RIMLS) and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, Geert Grooteplein Zuid 10, Nijmegen 6525 GA, The Netherlands; Department of Medical Genetics, Iuliu Hatieganu University if Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
Baziel G.M. van Engelen
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen 6525 GA, the Netherlands
Christopher R.S. Banerji
King’s College London, Randall Centre for Cell and Molecular Biophysics, New Hunt’s House, Guy’s Campus, London SE1 1UL, UK; The Alan Turing Institute, The British Library, 96 Euston Road, London NW1 2DB, UK; University College London Hospitals, NHS Foundation Trust, London NW1 2BU, UK
Peter S. Zammit
King’s College London, Randall Centre for Cell and Molecular Biophysics, New Hunt’s House, Guy’s Campus, London SE1 1UL, UK; Corresponding author
Summary: The routine need for myonuclear turnover in skeletal muscle, together with more sporadic demands for hypertrophy and repair, are performed by resident muscle stem cells called satellite cells. Muscular dystrophies are characterized by muscle wasting, stimulating chronic repair/regeneration by satellite cells. Here, we derived and validated transcriptomic signatures for satellite cells, myoblasts/myocytes, and myonuclei using publicly available murine single cell RNA-Sequencing data. Our signatures distinguished disease from control in transcriptomic data from several muscular dystrophies including facioscapulohumeral muscular dystrophy (FSHD), Duchenne muscular dystrophy, and myotonic dystrophy type I. For FSHD, the expression of our gene signatures correlated with direct counts of satellite cells on muscle sections, as well as with increasing clinical and pathological severity. Thus, our gene signatures enable the investigation of myogenesis in bulk transcriptomic data from muscle biopsies. They also facilitate study of muscle regeneration in transcriptomic data from human muscle across health and disease.
