A Comprehensive Atlas of Transcriptome Diversity in Mouse Skeletal Muscle

小鼠骨骼肌转录组多样性综合图谱

• 批准号: 9439594
• 负责人: Michael Evan Hughes
• 金额: $ 19.02万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-05 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9439594
• 关键词: Comprehensive; Atlas; Transcriptome; Diversity; Mouse

 DESCRIPTION (provided by applicant): Skeletal muscles are a diverse family of highly specialized tissues that perform a wide array of physiological functions. These muscles originate from different developmental origins and have characteristic, specialized morphologies. Unsurprisingly, many disorders of skeletal muscle afflict a remarkably specific subset of tissues. 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 support research into the causes, treatment, and prevention of musculoskeletal diseases. Nevertheless, most gene expression studies performed to-date have not directly addressed intrinsic variability among different muscle tissues. To better understand the intrinsic differences between muscle tissues, our long term goal is to build a comprehensive, publicly-available gene expression atlas. Our strategy is to use RNA-sequencing to profile the expression of mRNA and small non-coding RNAs in mouse muscle tissues. We will exploit the single-base resolution of RNA-sequencing data to study post-transcriptional regulatory mechanisms, such as alternative splicing and alternative polyadenylation. This proposal will thereby define transcriptional diversity within representative muscle tissues and make this resource available to the research and clinical community. These data will be a key reference for future studies of gene expression changes in disease, injury, and aging. Moreover, successful completion of this proposal will enable discovery-based approaches to identify and eventually manipulate tissue-specific factors that determine whether a given muscle group is susceptible to injury and disease.

 描述（由适用提供）：骨骼肌是一个高度专业的组织，可以执行各种物理功能。这些肌肉来自不同的发育起源，具有特征性的专业形态。毫不奇怪，骨骼肌的许多疾病都折磨着非常特定的组织子集。总体而言，这些观察结果表明，特定的遗传程序建立并维持肌肉时机的身体专业化。阐明这些遗传程序对于支持对肌肉骨骼疾病的原因，治疗和预防的研究至关重要。然而，大多数进行了迄今为止的基因表达研究并未直接解决不同肌肉时机之间的内在变异性。为了更好地了解肌肉时机之间的内在差异，我们的长期目标是建立一个全面的公开基因表达地图集。我们的策略是使用RNA测序来介绍小鼠肌肉组织中mRNA和小非编码RNA的表达。我们将利用RNA测序数据的单碱基分辨率来研究转录后调节机制，例如替代剪接和替代聚腺苷酸化。因此，该建议将定义代表肌肉组织中的转录多样性，并使研究和临床社区可用。这些数据将是对疾病，损伤和衰老基因表达变化的未来研究的关键参考。此外，该提案的成功完成将实现基于发现的方法来识别并最终操纵组织特异性因素，从而确定给定肌肉群是否容易受伤和疾病。