Microgravity influences maintenance of the human muscle stem/progenitor cell pool

• Published in: Biochemical and biophysical research communications Vol. 493; no. 2; pp. 998 - 1003
• Main Authors: Hosoyama, Tohru, Ichida, Shunji, Kanno, Masatsugu, Ishihara, Reiichi, Hatashima, Toshikatsu, Ueno, Koji, Hamano, Kimikazu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.11.2017
• Subjects: Cell Culture Techniques - instrumentation; Cell Culture Techniques - methods; Cell Line; Equipment Design; Human induced pluripotent stem cells; Humans; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; MAP Kinase Signaling System; Microgravity; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; PAX7 Transcription Factor - analysis; PAX7 Transcription Factor - metabolism; Skeletal muscle; Stem Cells - cytology; Stem Cells - metabolism; Stem/progenitor cells; Weightlessness; Human induced pluripotent stem cells; Microgravity; Stem/progenitor cells; Skeletal muscle
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.09.103

Microgravity induces skeletal muscle atrophy; however, the underlying mechanism is not clarified. In particular, the influence of microgravity on human skeletal muscle stem/progenitor cells (SMPCs) is not well understood. In this study, we used induced pluripotent stem cell-derived human SMPCs to investigate the effect of microgravity on maintenance of the stem/progenitor cell pool. Human SMPCs were induced by free-floating spherical aggregation culture, and derivatized-SMPC spheres were maintained in a microgravity condition (10−3 G) for 2 weeks using a clinostat rotation system. Microgravity culture deformed the SMPC spheres, with no signs of apoptosis. The most obvious change from microgravity culture was a significant decrease in the expression level of Pax7 in the SMPC spheres, with reduced numbers of myotubes in adhesion culture. Pax7 expression also decreased in the presence of the proteasome inhibitor MG132, indicating that the proteasomal degradation of Pax7 protein is not critical for its reduced expression in microgravity culture. Moreover, microgravity culture decreased the expression level of tumor necrosis factor receptor-associated factor 6 (TRAF6) and phosphorylation of its downstream molecule extracellular-related kinase (ERK) in SMPC spheres. Therefore, microgravity negatively regulates Pax7 expression in human SMPCs possibly through inhibition of the TRAF6/ERK pathway to consequently dysregulate SMPC pool maintenance. Overall, these results suggest that skeletal muscle atrophy is caused by microgravity-induced exhaustion of the stem cell pool. •Microgravity condition decreases Pax7 expression in human muscle stem/progenitor cell spheres.•Microgravity reduces stem cell pool in human muscle stem/progenitor cells.•Decreased Pax7 is not caused by proteasomal degradation in microgravity condition.•Microgravity decreases Pax7 expression in human muscle stem/progenitor cells possibly through ERK-mediated pathway.