Table_3_Meta-analysis of RNA-Seq datasets highlights novel genes/pathways involved in fat deposition in fat-tail of sheep.XLSX

IntroductionFat-tail in sheep is considered as an important energy reservoir to provide energy as a survival buffer during harsh challenges. However, fat-tail is losing its importance in modern sheep industry systems and thin-tailed breeds are more desirable. Using comparative transcriptome analysis to compare fat-tail tissue between fat- and thin-tailed sheep breeds provides a valuable approach to study the complex genetic factors associated with fat-tail development. However, transcriptomic studies often suffer from issues with reproducibility, which can be improved by integrating multiple studies based on a meta-analysis.MethodsHence, for the first time, an RNA-Seq meta-analysis on sheep fat-tail transcriptomes was performed using six publicly available datasets.Results and discussionA total of 500 genes (221 up-regulated, 279 down-regulated) were identified as differentially expressed genes (DEGs). A jackknife sensitivity analysis confirmed the robustness of the DEGs. Moreover, QTL and functional enrichment analysis reinforced the importance of the DEGs in the underlying molecular mechanisms of fat deposition. Protein-protein interactions (PPIs) network analysis revealed the functional interactions among the DEGs and the subsequent sub-network analysis led to identify six functional sub-networks. According to the results of the network analysis, down-regulated DEGs in green and pink sub-networks (like collagen subunits IV, V, and VI, integrins 1 and 2, SCD, SCD5, ELOVL6, ACLY, SLC27A2, and LPIN1) may impair lipolysis or fatty acid oxidation and cause fat accumulation in tail. On the other hand, up-regulated DEGs, especially those are presented in green and pink sub-networks (like IL6, RBP4, LEPR, PAI-1, EPHX1, HSD11B1, and FMO2), might contribute to a network controlling fat accumulation in the tail of sheep breed through mediating adipogenesis and fatty acid biosynthesis. Our results highlighted a set of known and novel genes/pathways associated with fat-tail development, which could improve the understanding of molecular mechanisms behind fat deposition in sheep fat-tail.

羊的肥尾被视为一项重要的能量储备，可在严苛挑战中提供生存缓冲能量。然而，在现代羊业体系中，肥尾的重要性正在逐渐降低，细尾品种更为人们所青睐。通过比较转录组分析，对比肥尾与细尾羊品种的肥尾组织，为研究与肥尾发育相关的复杂遗传因素提供了一种有价值的途径。然而，转录组研究往往面临着可重复性问题，这一问题可以通过基于元分析的多个研究的整合得到改善。方法上，首次对羊肥尾转录组进行了基于六个公开数据集的RNA-Seq元分析。结果与讨论中，共鉴定出500个差异表达基因（其中上调221个，下调279个），通过刀切敏感性分析证实了差异表达基因的稳定性。此外，QTL和功能富集分析强化了差异表达基因在脂肪沉积的分子机制中的重要性。蛋白质-蛋白质相互作用（PPI）网络分析揭示了差异表达基因之间的功能相互作用，并通过后续的子网络分析识别出六个功能子网络。根据网络分析结果，绿色和粉色子网络中下调的差异表达基因（如胶原蛋白亚单位IV、V和VI、整合素1和2、SCD、SCD5、ELOVL6、ACLY、SLC27A2和LPIN1）可能损害脂肪分解或脂肪酸氧化，导致尾部脂肪积累。另一方面，上调的差异表达基因，尤其是那些在绿色和粉色子网络中出现的基因（如IL6、RBP4、LEPR、PAI-1、EPHX1、HSD11B1和FMO2），可能通过介导脂肪生成和脂肪酸生物合成，参与控制羊品种尾部脂肪积累的调控网络。我们的研究结果突显了一组与肥尾发育相关的已知和新型基因/通路，这些结果有助于增进对羊肥尾脂肪沉积背后分子机制的深入理解。