TY - JOUR
T1 - Transcriptomic gene signatures measure satellite cell activity in muscular dystrophies
AU - Engquist, Elise
AU - Greco, Anna
AU - Joosten, Leo Ab
AU - van Engelen, Baziel G M
AU - Banerji, Chris
AU - Zammit, Peter
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/6/21
Y1 - 2024/6/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85193977943&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2024.109947
DO - 10.1016/j.isci.2024.109947
M3 - Article
SN - 2589-0042
VL - 27
JO - iScience
JF - iScience
IS - 6
M1 - 109947
ER -