Radiation-Induced Damage to Prepubertal Pax7+ Skeletal Muscle Stem Cells Drives Lifelong Deficits in Myofiber Size and Nuclear Number

John F Bachman; Roméo S Blanc; Nicole D Paris; Jacob G Kallenbach; Carl J Johnston; Eric Hernady; Jacqueline P Williams; Joe V Chakkalakal

doi:10.1016/j.isci.2020.101760

Radiation-Induced Damage to Prepubertal Pax7+ Skeletal Muscle Stem Cells Drives Lifelong Deficits in Myofiber Size and Nuclear Number

iScience. 2020 Nov 2;23(11):101760. doi: 10.1016/j.isci.2020.101760. eCollection 2020 Nov 20.

Authors

John F Bachman^{1

2}, Roméo S Blanc², Nicole D Paris², Jacob G Kallenbach^{2

3}, Carl J Johnston⁴, Eric Hernady⁵, Jacqueline P Williams^{5

6}, Joe V Chakkalakal^{2

3

6

7

8}

Affiliations

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 Engineering, University of Rochester, Rochester, NY, USA.
⁴ Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA.
⁵ Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, USA.
⁶ Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.
⁷ Stem Cell and Regenerative Medicine Institute, and The Rochester Aging Research Center, University of Rochester Medical Center, Rochester, NY, USA.
⁸ Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA.

Abstract

During prepubertal development, muscle stem cells (satellite cells, SCs) actively contribute to myofiber growth. Because some SCs are active during this time, they may be particularly susceptible to damage. Using a Small Animal Radiation Research Platform (SARRP), we investigated the effects of local fractionated radiation treatment on prepubertal SCs. Immediately after this regimen, there was a reduction in SC number. Although surviving SCs had deficiencies in function, some myogenic potential remained. Indeed, some muscle regenerative capacity persisted immediately after irradiation. Lastly, we assessed the long-term consequences of radiation-induced SC loss during prepuberty. We observed a reduction of myofiber size and corresponding loss of nuclei in both fast- and slow-contracting muscles 14 months post-irradiation. Notably, prepubertal SC depletion mimicked these lifelong deficits. This work highlights the susceptibility of prepubertal SCs to radiation exposure. We also reveal the importance of prepubertal SC contribution to the lifelong maintenance of skeletal muscle.

Keywords: Cancer; Cell Biology; Stem Cell Research.

Abstract

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