Professor Yamaguchi and Professor Shimozuru’s paper has been published in The FASEB Journal

December 1, 2025

PUBLICATIONS

A paper by Professor Yoshifumi Yamaguchi of Hokkaido University’s Institute of Low Temperature Science and Professor Michito Shimozuru of Hokkaido University’s Faculty of Veterinary Medicine has been published in The FASEB Journal.

Tatsuya Miyaji, Ryuichi Kasuya, Mayuko Monden, Yutaka Tamura, Michito Shimozuru, Toshio Tsubota, Daisuke Tsukamoto, Guangyuan Li, Shota Kawano, Yuri Watanabe, Yoshifumi Yamaguchi, Masatomo Watanabe, Mitsunori Miyazaki. Cold-Induced Suppression of Myogenesis in Skeletal Muscle Stem Cells Contributes to Delayed Muscle Regeneration During Hibernation. The FASEB Journal, 2025, Vol. 39, Issue 23, e71297.
DOI: https://doi.org/10.1096/fj.202502651R

Abstract

Mammalian hibernators experience profound cold stress and prolonged physical inactivity during torpor periods; however, it is unclear how skeletal muscle stem cells (satellite cells; SCs) respond to these challenges. In this study, we demonstrated that SCs from a mammalian hibernator, the Syrian hamster, exhibit remarkable resistance to cold-induced cell death, which is associated with intrinsically higher expression of the antioxidant enzyme GPX4, likely contributing to ferroptosis suppression. RNA-seq analysis revealed widespread downregulation of myogenesis-related genes following cold exposure, suggesting suppression of the myogenic program. Consistently, SCs exposed to cold stress exhibited reduced activation and differentiation capacity upon subsequent rewarming, with an increased number of quiescent Pax7-positive/MyoD-negative cells. Muscle regeneration was markedly delayed during hibernation, accompanied by decreased SC activation and macrophage infiltration, suggesting that cold-induced suppression of SC function underlies the limited regenerative capacity in hibernating hamsters. Our results provide insights into the unique physiology of mammalian hibernators: SC viability is preserved, whereas regenerative activity is selectively suppressed during hibernation.

Graphical Abstract

Hibernating mammals preserve satellite cell viability during extreme cold exposure by suppressing ferroptosis through elevated GPX4 expression. Although these cells survive cold stress, myogenic activation and differentiation are markedly reduced, leading to delayed muscle regeneration in vivo. Cold exposure shifts satellite cells toward a quiescent Pax7⁺/MyoD⁻ state, while regenerative and inflammatory responses are attenuated during hibernation. These findings highlight a dual strategy in which stem cell integrity is maintained but energy-demanding regenerative programs are selectively downregulated.