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PCM1 labeling reveals myonuclear and nuclear dynamics in skeletal muscle across species

Viggars, MR, Owens, DJ, Stewart, C, Coirault, C, Mackey, AL and Jarvis, JC (2022) PCM1 labeling reveals myonuclear and nuclear dynamics in skeletal muscle across species. American Journal of Physiology. Cell physiology, 324 (1). C85-C97. ISSN 0363-6143

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Abstract

Myonuclei transcriptionally regulate muscle fibers during homeostasis and adaptation to exercise. Their subcellular location and quantity are important when characterizing phenotypes of myopathies, the effect of treatments, and understanding the roles of satellite cells in muscle adaptation and muscle "memory." Difficulties arise in identifying myonuclei due to their proximity to the sarcolemma and closely residing interstitial cell neighbors. We aimed to determine to what extent (pericentriolar material-1) PCM1 is a specific marker of myonuclei in vitro and in vivo. Single isolated myofibers and cross sections from mice and humans were studied from several models including wild-type and Lamin A/C mutant mice after functional overload and damage and recovery in humans following forced eccentric contractions. Fibers were immunolabeled for PCM1, Pax7, and DNA. C2C12 myoblasts were also studied to investigate changes in PCM1 localization during myogenesis. PCM1 was detected at not only the nuclear envelope of myonuclei in mature myofibers and in newly formed myotubes but also centrosomes in proliferating myogenic precursors, which may or may not fuse to join the myofiber syncytium. PCM1 was also detected in nonmyogenic nuclei near the sarcolemma, especially in regenerating areas of the Lmna+/ΔK32 mouse and damaged human muscle. Although PCM1 is not completely specific to myonuclei, the impact that PCM1+ macrophages and interstitial cells have on myonuclei counts would be small in healthy muscle. PCM1 may prove useful as a marker of satellite cell dynamics due to the distinct change in localization during differentiation, revealing satellite cells in their quiescent (PCM1-), proliferating (PCM1+ centrosome), and prefusion states (PCM1+ nuclear envelope).

Item Type: Article
Uncontrolled Keywords: Muscle, Skeletal; Satellite Cells, Skeletal Muscle; Animals; Humans; Mice; Muscular Diseases; Cell Cycle Proteins; Cell Differentiation; Muscle Fibers, Skeletal; PCM1; hypertrophy; myonuclei; pericentriolar material-1; skeletal muscle; Mice; Humans; Animals; Muscle, Skeletal; Muscle Fibers, Skeletal; Muscular Diseases; Cell Differentiation; Satellite Cells, Skeletal Muscle; Cell Cycle Proteins; 0601 Biochemistry and Cell Biology; 0606 Physiology; 1116 Medical Physiology; Physiology
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QP Physiology
R Medicine > RC Internal medicine > RC1200 Sports Medicine
G Geography. Anthropology. Recreation > GV Recreation Leisure > GV561 Sports
Divisions: Sport & Exercise Sciences
Publisher: American Physiological Society
SWORD Depositor: A Symplectic
Date Deposited: 18 Jan 2023 11:57
Last Modified: 21 Dec 2023 00:50
DOI or ID number: 10.1152/ajpcell.00285.2022
URI: https://researchonline.ljmu.ac.uk/id/eprint/18671
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