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Development. 2018 Oct 10. pii: dev.167197. doi: 10.1242/dev.167197. [Epub ahead of print]

Prepubertal skeletal muscle growth requires Pax7-expressing satellite cell-derived myonuclear contribution.

Author information

1
Department of Pathology and Laboratory Medicine, Cell Biology of Disease Graduate Program, University of Rochester Medical Center, Rochester NY, USA.
2
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester NY, USA.
3
Department of Biomedical Genetics, Genetics, Development, and Stem Cells Graduate Program, University of Rochester Medical Center, Rochester NY, USA.
4
Current address Genea Biocells US Inc., San Diego, CA, USA.
5
Department of Orthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester NY, USA.
6
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester NY, USA joe_chakkalakal@urmc.rochester.edu.
7
Wilmot Cancer Institute, Stem Cell and Regenerative Medicine Institute, and The Rochester Aging Research Center, University of Rochester Medical Center, Rochester NY, USA.

Abstract

The functional role of Pax7-expressing satellite cells (SCs) to postnatal skeletal muscle development beyond weaning remains obscure. Therefore, the relevance of SCs during prepubertal growth, a period after weaning but prior to the onset of puberty, has not been examined. Here, we have characterized skeletal muscle growth during prepuberty and found significant increases in myofiber cross-sectional area that correlated with SC-derived myonuclear number. Remarkably, genome-wide RNA sequencing analysis established that post-weaning juvenile and early adolescent skeletal muscle have markedly different gene expression signatures. These distinctions are consistent with extensive skeletal muscle maturation during this essential, albeit brief, developmental phase. Indelible labeling of SCs with Pax7 CreERT2/+; Rosa26 nTnG/+ (P7nTnG) mice demonstrated extensive SC-derived myonuclear contribution during prepuberty, with a substantial reduction at puberty onset. Prepubertal depletion of SCs in Pax7 CreERT2/+; Rosa26 DTA/+ (P7DTA) mice reduced myofiber size, myonuclear number, and caused force generations deficits, to a similar extent, in both fast and slow-contracting muscles. Collectively, these data demonstrate SC-derived myonuclear accretion as a cellular mechanism that contributes to prepubertal hypertrophic skeletal muscle growth.

KEYWORDS:

Aging; Atrophy; Musculoskeletal; Pediatric; Regeneration; Stem cell

PMID:
30305290
DOI:
10.1242/dev.167197
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