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Transcriptional profiling of skeletal muscle during hypertrophy in the absence of satellite cell participation reveals muscle‐specific diversity and satellite cell dependent signaling networks
Author(s) -
Englund Davis A.,
Figueiredo Vandre,
dungan cory,
Murach Kevin,
Peck Bailey,
Dupont Alec,
McCarthy John,
Peterson Charlotte
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.00247
Subject(s) - muscle hypertrophy , plantaris muscle , satellite , soleus muscle , biology , skeletal muscle , extracellular matrix , cell , medicine , endocrinology , cell growth , myocyte , microbiology and biotechnology , biochemistry , engineering , aerospace engineering
The role of satellite cells (muscle stem cells) during hypertrophic growth remains to be fully elucidated. Previous findings are limited due to the mode of mechanical overload and a relatively narrow analysis of downstream effectors influenced by satellite cell depletion. The current study was designed to determine how the absence of satellite cells influences the transcriptome‐wide response and phenotypic adaptation to short‐ and long‐term periods of muscle growth in the oxidative soleus and the glycolytic/oxidative plantaris. We administered vehicle (SC+) or tamoxifen (SC−) to adult (6 months old) female Pax7‐DTA mice for 5 consecutive days to effectively deplete satellite cells. Following a 2‐week washout period, mice were subjected to progressive weighted wheel running (PoWeR) for 4 or 8 weeks or served as sedentary (locked running wheel) controls. After 4 and 8 weeks of PoWeR satellite cell and myonuclear density were significantly increased only in the muscles of SC+ mice. While muscle fiber size increased in both groups, growth was blunted at 4 and 8 weeks in the soleus and at 8 weeks in the plantaris of SC− mice. Further, measures of collagen demonstrate impaired extracellular matrix remodeling during muscle adaptation at both time points in the absence of satellite cells. RNA‐sequencing of the soleus and plantaris revealed muscle‐specific differences in the response to PoWeR as well as a dysregulated transcriptional profile during growth in the absence of satellite cells. These findings indicate satellite cells are required for optimal muscle growth and likely play a role in coordinating an efficacious transcriptional response for adaptations to exercise. We plan to further interrogate these findings at the myonuclear level via single‐nuclear sequencing, enabling a more targeted and fiber type‐specific analysis of signaling cascades dysregulated in the absence of satellite cell participation. Support or Funding Information Supported by AG060701 and AG049806 to CAP and JJM, AR071753 to KAM and TL1 TR001997 to DAE