Transcriptional Profiling Reveals Extraordinary Diversity Among Skeletal Muscle Tissues

Skeletal muscles are a diverse family of highly specialized tissues that perform a wide array of physiological activities and maintain whole-body glucose metabolism and energy homeostasis. Functional diversity is a distinctive feature of muscle tissues, which demonstrate remarkable variability in their speed of contraction, metabolic profile, resistance to fatigue, and regenerative capacity. Unsurprisingly, many disorders of skeletal muscle afflict a remarkably specific subset of tissues, including muscular dystrophies, cancer cachexia, aging sarcopenia, and amyotrophic lateral sclerosis. Taken as a whole, these observations indicate that specific genetic programs establish and maintain physiological specialization of muscle tissues. Elucidating these genetic programs is essential to understanding muscle specialization and propensity for disease. Nevertheless, most global profiling studies performed to-date have not directly addressed intrinsic variability between different muscle tissues. This gap in the literature is particularly glaring for more sophisticated mechanisms of gene expression regulation such as circadian control, post-transcriptional regulation and non-coding RNA expression, despite their well-established roles in many disease mechanisms. In an effort to understand the variability present within specific skeletal muscles with respect to gene expression, our lab has performed RNA-Seq on a variety of skeletal muscle tissues.骨骼肌（Skeletal muscles）是一类高度特化的多样化组织，可执行多种生理活动，并维持全身葡萄糖代谢与能量稳态。功能多样性是肌肉组织的显著特征，其在收缩速度、代谢谱、抗疲劳能力及再生能力上均表现出显著异质性。不难发现，诸多骨骼肌疾病仅累及特定的组织亚群，例如肌营养不良症、癌症恶病质、衰老性肌肉减少症及肌萎缩侧索硬化症。综合上述观察结果可知，特定的遗传程序可建立并维持肌肉组织的生理特化状态。阐明此类遗传程序，对于解析肌肉特化机制与疾病易感性均具有重要意义。然而，迄今已开展的绝大多数全局表达谱分析研究，均未直接针对不同骨骼肌组织间的内在异质性展开探究。现有研究在该领域的空白在基因表达调控的复杂机制中尤为突出，例如昼夜节律调控、转录后调控及非编码RNA表达——尽管这些机制在诸多疾病发病机制中的作用已得到充分证实。为探究特定骨骼肌组织内基因表达层面的异质性，本课题组已针对多种骨骼肌组织完成了RNA测序（RNA-Seq）实验。