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: 9182418
• 负责人: Michael Evan Hughes
• 金额: $ 5.58万
• 依托单位: UNIVERSITY OF MISSOURI-ST. LOUIS
• 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 2017-01-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9182418
• 关键词: Address; Affect; Aging; Alternative Splicing; Amyotrophic Lateral Sclerosis; Animals; Atlases; Brain; Breathing; Characteristics; Clinical; Communities; Data; Databases; Denervation; Development; Disease; Duchenne muscular dystrophy; Dystrophin; Equilibrium; Exhibits; Eye; Facial Muscles; Family; Fatigue; Female; Fiber; Future; Gene Expression; Gene Expression Profiling; Genes; Genetic; Genetic Programming; Genetic Transcription; Glare; Goals; HIV; Hereditary Disease; Injury; Laminin; Left; Lesion; Limb structure; Measures; Messenger RNA; MicroRNAs; Molecular Profiling; Morphology; Movement; Mus; Muscle; Muscular Atrophy; Muscular Dystrophies; Musculoskeletal Diseases; Neuromuscular Junction; Nucleotides; Online Systems; Orphan; Patients; Pattern; Physiological; Polyadenylation; Post-Transcriptional Regulation; Posture; Predisposition; Prevention; RNA Editing; RNA Sequence Analysis; Rattus; Research; Research Support; Resistance; Resolution; Resources; Respiratory Diaphragm; Role; Sarcoglycans; Sepsis; Skeletal Muscle; Skeletal muscle structure of neck; Small RNA; Speed; Statistical Methods; Testing; Tissues; Transcript; Untranslated RNA; Untranslated Regions; base; cancer cachexia; differential expression; disease mechanisms study; distributed data; follow-up; mRNA Expression; male; metabolic profile; orbit muscle; programs; regenerative; sarcopenia; transcriptome; transcriptome sequencing

Project Summary: 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 test hypotheses regarding specific post-transcriptional regulatory mechanisms, such as alternative splicing, RNA editing, 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.

项目摘要： 骨骼肌是一个高度专业的组织的多元化家族，可以进行广泛的阵列 生理功能。这些肌肉来自不同的发育起源，具有特征， 专业形态。毫不奇怪，骨骼肌的许多疾病都非常具体 组织子集。从整体上看，这些观察结果表明特定的遗传程序建立和 维持肌肉组织的生理专业化。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。尽管如此，大多数 进行了迄今为止的基因表达研究没有直接解决不同的不同 肌肉组织。为了更好地了解肌肉组织之间的内在差异，我们的长期目标是 建立一个全面的，公共可用的基因表达地图集。我们的策略是使用RNA测序 介绍了小鼠肌肉组织中mRNA和小非编码RNA的表达。我们将利用 RNA测序数据的单基碱分辨率以测试有关特定转录后的假设 调节机制，例如替代剪接，RNA编辑和替代聚腺苷酸化。这 提案将在代表性肌肉组织中定义转录多样性，并做到这一点 研究和临床社区可用的资源。这些数据将是未来的关键参考 研究基因表达在疾病，损伤和衰老中的变化。而且，成功完成 提案将实现基于发现的方法，以识别并最终操纵组织特异性因素 这决定了给定的肌肉群是否容易受伤和疾病。