PI3K/Akt通路调控猪肌肉发育及产肉量的整合表观遗传学机制

Improving the meat production, which depends on muscle growth and development，is the main goal of the pig breeding. Vast differences of meat production between different types (lean-type, fat-type and mini-type) of pigs provide good material for the molecular mechanism research. It is relatively explicit that PI3K/Akt plays an important function in regulating muscle growth and development in the field of medicine and model animals, but the mechanism of how does it regulate the meat production remain unclear, especially epigenetic mechanism is poorly understood. The preliminary work of our group revealed different types of pigs showed significantly different PI3K/Akt epigenetic mechanism in muscle, so we put forward a scientific hypothesis that “Epigenetic factors affect the growth and development of muscle in different pig breeds by regulating PI3K/Akt pathway”. In this project, information of genes, miRNA, LncRNA and methylation status involved in muscle PI3K/Akt pathway throughout 28 developmental time points before and after birth in three types of pigs will be integrated to discover their mutual relationship at molecular, cellular and individual developmental levels, and to construct the integrated network diagrams and identify the key genes and epigenetic factors. This project will lead to a better understanding about the mechanism of P13K/Akt and epigenetic factors within three types of pigs with different meat production, thus validation and elucidation of our scientific hypothesis. The genetic and epigenetics basis for meat production traits will be revealed, this will provide theoretical basis for improvement of meat production and cultivating of new pig breeds in China.

提高产肉量是猪育种主要目标，产肉量取决于肌肉生长发育。不同类型（瘦肉型、脂肪型和矮小型）猪产肉量差异巨大，为相关分子机制研究提供了良好素材。PI3K/Akt通路的重要功能在医学及模式动物领域已较为明确，但其调控猪产肉量的机制尚不清楚，特别是表观机制知之甚少。本组前期研究初步显示不同类型猪肌肉PI3K/Akt表观机制显著不同，提出“表观遗传调控P13K/Akt通路影响不同表型猪肌肉生长发育”的科学假设。本项目将整合三类型猪出生前后28个生长发育点肌肉PI3K/Akt通路基因、miRNA、LncRNA和甲基化信息，在分子、细胞和个体发育水平揭示其相互关系，构建整合网络图，确定关键基因及表观因子，阐明P13K/Akt及表观因子在三类型猪产肉量差异形成中的作用机制，验证并阐释本组提出的科学假说。揭示猪产肉量性状形成的遗传和表观遗传学基础，为我国猪产肉量提高及新品种培育提供理论基础。

为揭示猪产肉量形成的遗传和表观遗传机制，系统分析了产肉量差异显著的3种猪长白（瘦肉型）、通城（脂肪型）和五指山猪（矮小型）28个出生前后生长发育时间点骨骼肌多组学信息（甲基化，lncRNA，miRNA，circRNA等）。整合多组学数据，进行了PI3K/Akt通路及表观因子的整合表观遗传分析及多层次网络构建，鉴定了该通路调控骨骼肌发育的关键调控因子，确定了关键基因与表观因子之间的整合表观互作。分析了该通路基因及表观遗传因子CNN3、PDK1、FoxO3、miRNA200、miRNA486等对于肌细胞增殖、分化等的影响，阐明了其生物学功能。在资源群体中测定收集初生重、日增重、背膘厚、瘦肉率等产肉性状，利用MassArray进行SNP分型，确定通路基因及表观因子对产肉量的遗传效应，鉴定出10余个可用于遗传改良的候选基因和标记。本项目通过3类型猪种间、骨骼肌不同发育时间点、细胞及个体水平的多组学整合比较，揭示了PI3K/AKT 信号通路相关基因及表观因子调控骨骼肌生长发育的详细分子机制。基于本项目研究结果，提出动物多组学精准育种新观点。部分成果已用于猪新品种培育。国际刊物发表论文18篇；申请国家发明专利3项，其中授权2项；构建数据库1个，并获软件著作权；培养研究生12名；成功举办学术研讨会1次。