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标题：Radiation-Induced Damage to Prepubertal Pax7+ Skeletal Muscle Stem Cells Drives Lifelong Deficits in Myofiber Size and Nuclear Number
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作者：John F. Bachman ; Roméo S. Blanc ; Nicole D. Paris 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：11
页码：1-34
DOI：10.1016/j.isci.2020.101760
语种：English
出版社：Elsevier
摘要：SummaryDuring 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.Graphical AbstractDisplay OmittedHighlights•Increased sensitivity of satellite cells to irradiation during prepubertal growth•Prepubertal irradiation leads to lifelong deficits in skeletal muscle regenerative capacity•Lifelong reduction in myofiber size and nuclear number is a consequence of prepubertal irradiation•Satellite cell ablation mimics the lifelong effects of prepubertal irradiation on myofiber size and nuclear numberCell Biology; Stem Cell Research; Cancer