Satellite Cell Depletion Disrupts Transcriptional Coordination and Muscle Adaptation to Exercise.
Satellite Cell Depletion Disrupts Transcriptional Coordination and Muscle Adaptation to Exercise.
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卫星细胞耗竭会破坏转录协调和肌肉适应运动。
DOI：
10.1093/function/zqaa033
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Peterson CA
中科院分区：
文献类型：
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作者：
Englund DA;Figueiredo VC;Dungan CM;Murach KA;Peck BD;Petrosino JM;Brightwell CR;Dupont AM;Neal AC;Fry CS;Accornero F;McCarthy JJ;Peterson CA
卫星细胞是出生后发育、整个生命周期中骨骼肌再生以及成熟前骨骼肌肥大所必需的。我们小组的目标是解决成熟骨骼肌的肥大生长是否需要卫星细胞。在这里，我们对在存在或不存在卫星细胞的情况下适应运动过程中的骨骼肌进行了全面的表征和转录组分析，以便识别受卫星细胞内容影响的不同表型和基因网络。我们给成年 Pax7-DTA 小鼠注射载体或他莫昔芬，并让它们进行渐进式负重轮跑 (PoWeR)。然后，我们对媒介物 (SC+) 和他莫昔芬治疗的 (SC−) 小鼠进行免疫组织化学分析和全肌肉 RNA 测序。此外，我们进行了单肌核 RNA 测序，以提供有关卫星细胞融合如何影响肌核转录的详细信息。我们发现，虽然在没有卫星细胞的情况下骨骼肌可以对 PoWeR 产生强烈的肥大反应，但生长和适应最终会减弱。转录分析揭示了在卫星细胞缺失的情况下，肌肉适应的几个关键基因网络发生了改变。
Satellite cells are required for postnatal development, skeletal muscle regeneration across the lifespan, and skeletal muscle hypertrophy prior to maturity. Our group has aimed to address whether satellite cells are required for hypertrophic growth in mature skeletal muscle. Here, we generated a comprehensive characterization and transcriptome-wide profiling of skeletal muscle during adaptation to exercise in the presence or absence of satellite cells in order to identify distinct phenotypes and gene networks influenced by satellite cell content. We administered vehicle or tamoxifen to adult Pax7-DTA mice and subjected them to progressive weighted wheel running (PoWeR). We then performed immunohistochemical analysis and whole-muscle RNA-seq of vehicle (SC+) and tamoxifen-treated (SC−) mice. Further, we performed single myonuclear RNA-seq to provide detailed information on how satellite cell fusion affects myonuclear transcription. We show that while skeletal muscle can mount a robust hypertrophic response to PoWeR in the absence of satellite cells, growth, and adaptation are ultimately blunted. Transcriptional profiling reveals several gene networks key to muscle adaptation are altered in the absence of satellite cells.